Glioma
Conditions
Brief summary
This single arm study will assess the maximum tolerated dose, and dose-limiting toxicities, of Xeloda administered concurrently with radiation therapy, in children with newly diagnosed diffuse intrinsic brain stem gliomas and high grade gliomas. Xeloda will be administered twice daily, at a starting dose of 500mg/m2 bid, beginning within 24 hours of the start of radiation therapy. Subsequent dose escalations will be in increments of 30%, using a standard dose escalation schema. Post-radiation therapy with Xeloda will continue after a 2 week break. The anticipated time on study treatment is 3-12 months, and the target sample size will not exceed 30 evaluable patients.
Interventions
DRUGcapecitabine [Xeloda]
500mg/m2 po bid (starting dose)
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* patients \>=3 and \<=21 years of age; * newly diagnosed non-disseminated brainstem glioma or non-disseminated high grade glioma; * Karnofsky (if \>16 years) or Lansky (if \< 16 years) Performance Scale of \>=50%; * adequate organ function.
Exclusion criteria
* previous chemotherapy, radiation therapy, immunotherapy or bone marrow transplant; * uncontrolled infection; * known DPD deficiency.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Up to 06 years | For blood chemistry, the parameters assessed were: Sodium, potassium, calcium, magnesium, chloride, bicarbonate, total protein, albumin, alkaline phosphatase, alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), Lactate dehydrogenase (LDH), total bilirubin, direct bilirubin, indirect bilirubin, creatinine (serum creatinine or creatinine clearance), glucose. |
| Maximum Tolerated Dose (MTD) of Capecitabine. | Upto 11 weeks. | The MTD was the dose level at which six evaluable patients had been treated and at most one patient experienced a dose limiting toxicity (DLT) and the next highest dose level was too toxic. Dose escalation occurred if 0 out of 3 or at most 1 out of 6 patients experienced DLT while being treated at a dose level; otherwise the dose was declared unsafe and thus above the MTD. |
| Dose Limiting Toxicities (DLTs) | Upto 11 weeks | DLT was defined as any of the following events occurring during the 11 week dose-finding period: any event that leads to interruption of planned radiation for 5 consecutive days or 10 days total; Grade 4 neutropenia or thrombocytopenia; Grade 3 thrombocytopenia that required a platelet transfusion on 2 or more occasions; any Grade 3 or 4 non-hematologic toxicity (with the exception of grade 3 nausea or vomiting of less than 5 days duration, Grade 3 transaminases that returned to baseline value within 7 days of study drug interruption and that did not recur upon re-challenge with study drug, and/or Grade 3 fever or infection of \<5 days duration); Grade 2 non-hematologic toxicities that persisted for \>7 days and required treatment interruption, or any other capecitabine-related adverse events that required need for dose reduction or permanent cessation of therapy, interruption of study drug for \>7 days or recurred on re-challenge with capecitabine rapidly disintegrating tablets (RDTs). |
| Number of Participants With Adverse Events (AE) | Up to 06 years | An AE is an unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Toxicity was monitored and graded according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Adverse events that were not included in the CTCAEv3.0 were reported and graded under the other AE within the appropriate category. |
| Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Up to 06 years | For hematology, the parameters assessed were: Hemoglobin, hematocrit, platelet count, RBC, WBC, lymphocytes, monocytes,granulocytes (blasts), neutrophils(segs, bands),eosinophils and basophils. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | Day 1 and Day 14 | Tmax is the corresponding time at which Cmax occurs of capecitabine and its metabolites.Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline \[pre-dose\], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline \[pre-dose\], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing). |
| The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | Day 1 and Day 14 | AUC last concentration of capecitabine and its metabolites. Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline \[pre-dose\], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline \[pre-dose\], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing). |
| Anti Tumor Activity | Up to 6 years | Tumor response refers to the best response prior to failure (disease progression, death or second malignancy). |
| Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | Day 1 and Day 14 | The maximum observed plasma concentration of capecitabine and its metabolites. Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline \[pre-dose\], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline \[pre-dose\], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing). |
Countries
United States
Participant flow
Recruitment details
All participants in the study were enrolled at Pediatric Brain Tumor Consortium (PBTC) institutions in the United States of America (USA), from 24 May 2007 through 27 October 2009.
Pre-assignment details
The study consisted of two periods of dosing: A dose-finding treatment period of 11 weeks and a post radiation treatment phase that lasted for 9 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Capecitabine 500 mg/m^2 Capecitabine 500 mg/m\^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy. | 4 |
| Capecitabine 650 mg/m^2 Capecitabine 650 mg/m\^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy. | 14 |
| Capecitabine 850 mg/m^2 Capecitabine 850 mg/m\^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy. | 6 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 3 | 3 | 4 |
| Overall Study | Failure to return | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Violation of selection criteria at entry | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 | Total |
|---|---|---|---|---|
| Age, Continuous | 7.5 years STANDARD_DEVIATION 1.73 | 8.4 years STANDARD_DEVIATION 2.65 | 13 years STANDARD_DEVIATION 3.41 | 9.37 years STANDARD_DEVIATION 3.39 |
| Gender Female | 1 Participants | 12 Participants | 2 Participants | 15 Participants |
| Gender Male | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 4 | 12 / 12 | 6 / 6 |
| serious Total, serious adverse events | 2 / 4 | 1 / 12 | 3 / 6 |
Outcome results
Primary
Dose Limiting Toxicities (DLTs)
DLT was defined as any of the following events occurring during the 11 week dose-finding period: any event that leads to interruption of planned radiation for 5 consecutive days or 10 days total; Grade 4 neutropenia or thrombocytopenia; Grade 3 thrombocytopenia that required a platelet transfusion on 2 or more occasions; any Grade 3 or 4 non-hematologic toxicity (with the exception of grade 3 nausea or vomiting of less than 5 days duration, Grade 3 transaminases that returned to baseline value within 7 days of study drug interruption and that did not recur upon re-challenge with study drug, and/or Grade 3 fever or infection of \<5 days duration); Grade 2 non-hematologic toxicities that persisted for \>7 days and required treatment interruption, or any other capecitabine-related adverse events that required need for dose reduction or permanent cessation of therapy, interruption of study drug for \>7 days or recurred on re-challenge with capecitabine rapidly disintegrating tablets (RDTs).
Time frame: Upto 11 weeks
Population: The safety population consisted of all eligible patients who received at least one dose of capecitabine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine (Overall) | Dose Limiting Toxicities (DLTs) | 0 Participants |
| Capecitabine 650 mg/m^2 | Dose Limiting Toxicities (DLTs) | 3 Participants |
| Capecitabine 850 mg/m^2 | Dose Limiting Toxicities (DLTs) | 3 Participants |
Primary
Maximum Tolerated Dose (MTD) of Capecitabine.
The MTD was the dose level at which six evaluable patients had been treated and at most one patient experienced a dose limiting toxicity (DLT) and the next highest dose level was too toxic. Dose escalation occurred if 0 out of 3 or at most 1 out of 6 patients experienced DLT while being treated at a dose level; otherwise the dose was declared unsafe and thus above the MTD.
Time frame: Upto 11 weeks.
Population: The safety population consisted of all eligible patients who received at least one dose of capecitabine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine (Overall) | Maximum Tolerated Dose (MTD) of Capecitabine. | 650 milligrams |
Primary
Number of Participants With Adverse Events (AE)
An AE is an unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Toxicity was monitored and graded according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Adverse events that were not included in the CTCAEv3.0 were reported and graded under the other AE within the appropriate category.
Time frame: Up to 06 years
Population: The safety population consisted of all eligible patients who received at least one dose of capecitabine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine (Overall) | Number of Participants With Adverse Events (AE) | 3 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Adverse Events (AE) | 12 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Adverse Events (AE) | 6 Participants |
Primary
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
For blood chemistry, the parameters assessed were: Sodium, potassium, calcium, magnesium, chloride, bicarbonate, total protein, albumin, alkaline phosphatase, alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), Lactate dehydrogenase (LDH), total bilirubin, direct bilirubin, indirect bilirubin, creatinine (serum creatinine or creatinine clearance), glucose.
Time frame: Up to 06 years
Population: The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Protein, normal to high, n=1,0,2 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Bicarbonate, normal to low, n=3,0,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Fasting glucose, normal to high, n=1,0,4 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Lactic dehydrogenase, normal to low, n=0,0,0 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Protein, normal to low, n=1,0,2 | 1 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Lactic dehydrogenase, normal to high, n=0,0,0 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Potassium, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Indirect bilirubin, normal to low, n=1,1,1 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Phosphate, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Fasting glucose, normal to low, n=1,0,4 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Indirect bilirubin, normal to high, n=1,1,1 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Serum albumin, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | BUN, normal to low, n=3,1,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Total bilirubin, normal to high, n=4,2,6 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | BUN, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Chloride, normal to low, n=3,1,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Total bilirubin, normal to low, n=4,2,6 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Alkaline phosphatase, normal to low, n=1,1,4 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Calcium, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Alkaline phosphatase, normal to high, n=1,1,4 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Direct blirubin, normal to low, n=2,1,1 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | ALAT (SGPT), normal to high, n=4,2,6 | 2 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Bicarbonate, normal to high, n=3,0,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Calcium, normal to low, n=3, 1,5 | 1 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Phosphate, normal to low, n=3,1,5 | 1 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Magnesium, normal to high, n=3,1,5 | 1 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Direct bilirubin, normal to high, n=2,1,1 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | ALAT (SGPT), normal to low, n=4,2,6 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Potassium, normal to low, n=3, 1,5 | 2 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Chloride, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | ASAT (SGOT), normal to high, n=1,0,4 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Sodium, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | ASAT (SGOT), normal to low, n=1,0,4 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Sodium, normal to low, n=3,1,5 | 1 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Serum creatinine, normal to high, n=4,2,6 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Magnesium, normal to low, n=3,1,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Serum creatinine, normal to low, n=4,2,6 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Serum albumin, normal to low, n=3,1,5 | 2 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Protein, normal to low, n=1,0,2 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Lactic dehydrogenase, normal to low, n=0,0,0 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Direct blirubin, normal to low, n=2,1,1 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Direct bilirubin, normal to high, n=2,1,1 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Serum albumin, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Serum creatinine, normal to low, n=4,2,6 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Serum creatinine, normal to high, n=4,2,6 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | ALAT (SGPT), normal to low, n=4,2,6 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Phosphate, normal to low, n=3,1,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Phosphate, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Potassium, normal to low, n=3, 1,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Potassium, normal to high, n=3,1,5 | 1 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Sodium, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Bicarbonate, normal to low, n=3,0,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Lactic dehydrogenase, normal to high, n=0,0,0 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Indirect bilirubin, normal to low, n=1,1,1 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Indirect bilirubin, normal to high, n=1,1,1 | 1 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | BUN, normal to low, n=3,1,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | BUN, normal to high, n=3,1,5 | 1 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Alkaline phosphatase, normal to low, n=1,1,4 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Alkaline phosphatase, normal to high, n=1,1,4 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Total bilirubin, normal to low, n=4,2,6 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Total bilirubin, normal to high, n=4,2,6 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Fasting glucose, normal to low, n=1,0,4 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Fasting glucose, normal to high, n=1,0,4 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Protein, normal to high, n=1,0,2 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Serum albumin, normal to low, n=3,1,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | ASAT (SGOT), normal to low, n=1,0,4 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | ASAT (SGOT), normal to high, n=1,0,4 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | ALAT (SGPT), normal to high, n=4,2,6 | 2 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Calcium, normal to low, n=3, 1,5 | 1 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Calcium, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Sodium, normal to low, n=3,1,5 | 1 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Magnesium, normal to low, n=3,1,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Magnesium, normal to high, n=3,1,5 | 1 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Chloride, normal to low, n=3,1,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Chloride, normal to high, n=3,1,5 | 1 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Bicarbonate, normal to high, n=3,0,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Total bilirubin, normal to low, n=4,2,6 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Serum albumin, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Magnesium, normal to low, n=3,1,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Sodium, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Potassium, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Indirect bilirubin, normal to high, n=1,1,1 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | ASAT (SGOT), normal to low, n=1,0,4 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Potassium, normal to low, n=3, 1,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Direct blirubin, normal to low, n=2,1,1 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | ASAT (SGOT), normal to high, n=1,0,4 | 2 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Phosphate, normal to high, n=3,1,5 | 1 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | ALAT (SGPT), normal to low, n=4,2,6 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Serum creatinine, normal to high, n=4,2,6 | 2 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Bicarbonate, normal to high, n=3,0,5 | 3 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | ALAT (SGPT), normal to high, n=4,2,6 | 4 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Magnesium, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Calcium, normal to low, n=3, 1,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Serum creatinine, normal to low, n=4,2,6 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Alkaline phosphatase, normal to high, n=1,1,4 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Calcium, normal to high, n=3,1,5 | 1 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Alkaline phosphatase, normal to low, n=1,1,4 | 1 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Phosphate, normal to low, n=3,1,5 | 1 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Direct bilirubin, normal to high, n=2,1,1 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | BUN, normal to high, n=3,1,5 | 1 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Serum albumin, normal to low, n=3,1,5 | 1 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | BUN, normal to low, n=3,1,5 | 2 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Protein, normal to high, n=1,0,2 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Total bilirubin, normal to high, n=4,2,6 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Indirect bilirubin, normal to low, n=1,1,1 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Fasting glucose, normal to low, n=1,0,4 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Lactic dehydrogenase, normal to high, n=0,0,0 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Fasting glucose, normal to high, n=1,0,4 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Lactic dehydrogenase, normal to low, n=0,0,0 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Bicarbonate, normal to low, n=3,0,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Protein, normal to low, n=1,0,2 | 1 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Chloride, normal to high, n=3,1,5 | 1 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Sodium, normal to low, n=3,1,5 | 3 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters | Chloride, normal to low, n=3,1,5 | 1 Participants |
Primary
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
For hematology, the parameters assessed were: Hemoglobin, hematocrit, platelet count, RBC, WBC, lymphocytes, monocytes,granulocytes (blasts), neutrophils(segs, bands),eosinophils and basophils.
Time frame: Up to 06 years
Population: The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | White blood cell, normal to high, n=3,1,5 | 1 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Monocytes (relative), normal to high, n=3,1,4 | 1 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Neutrophils (segmented), normal to high, n=3,0,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | White blood cell, normal to low, n=3,1,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Eosinophils (relative), normal to high, n=1,1,3 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Eosinophils (relative), normal to low, n=1,1,3 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Platelets, normal to high, n=4,2,6 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Haematocrit, normal to low, n=3,1,5 | 2 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Red blood cells, normal to low, n=3,1,3 | 2 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Hemoglobin, normal to high, n=4,2,6 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Haematocrit, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Basophils (relative), normal to low, n=0,1,2 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Hemoglobin, normal to low, n=4,2,6 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Lymphocytes (relative), normal to high, n=3,1,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Neutrophils (segmented), normal to low , n=3,0,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Platelets, normal to low, n=4,2,6 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Lymphocytes (relative), normal to low, n=3,1,5 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Red blood cells, normal to high, n=3,1,3 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Monocytes (relative), normal to low, n=3,1,4 | 0 Participants |
| Capecitabine (Overall) | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Basophils (relative), normal to high, n=0,1,2 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Hemoglobin, normal to high, n=4,2,6 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Platelets, normal to high, n=4,2,6 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Red blood cells, normal to high, n=3,1,3 | 1 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Neutrophils (segmented), normal to low , n=3,0,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Neutrophils (segmented), normal to high, n=3,0,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Basophils (relative), normal to low, n=0,1,2 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Basophils (relative), normal to high, n=0,1,2 | 1 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Lymphocytes (relative), normal to low, n=3,1,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Monocytes (relative), normal to low, n=3,1,4 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Monocytes (relative), normal to high, n=3,1,4 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Eosinophils (relative), normal to high, n=1,1,3 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Haematocrit, normal to low, n=3,1,5 | 1 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Haematocrit, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Hemoglobin, normal to low, n=4,2,6 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | White blood cell, normal to low, n=3,1,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | White blood cell, normal to high, n=3,1,5 | 1 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Platelets, normal to low, n=4,2,6 | 1 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Red blood cells, normal to low, n=3,1,3 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Lymphocytes (relative), normal to high, n=3,1,5 | 0 Participants |
| Capecitabine 650 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Eosinophils (relative), normal to low, n=1,1,3 | 1 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Red blood cells, normal to high, n=3,1,3 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | White blood cell, normal to low, n=3,1,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Monocytes (relative), normal to low, n=3,1,4 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Red blood cells, normal to low, n=3,1,3 | 1 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | White blood cell, normal to high, n=3,1,5 | 1 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Basophils (relative), normal to high, n=0,1,2 | 2 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Lymphocytes (relative), normal to high, n=3,1,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Platelets, normal to low, n=4,2,6 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Platelets, normal to high, n=4,2,6 | 1 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Neutrophils (segmented), normal to high, n=3,0,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Monocytes (relative), normal to high, n=3,1,4 | 3 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Basophils (relative), normal to low, n=0,1,2 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Neutrophils (segmented), normal to low , n=3,0,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Haematocrit, normal to high, n=3,1,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Lymphocytes (relative), normal to low, n=3,1,5 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Hemoglobin, normal to low, n=4,2,6 | 2 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Haematocrit, normal to low, n=3,1,5 | 4 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Eosinophils (relative), normal to high, n=1,1,3 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Hemoglobin, normal to high, n=4,2,6 | 0 Participants |
| Capecitabine 850 mg/m^2 | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters | Eosinophils (relative), normal to low, n=1,1,3 | 0 Participants |
Secondary
Anti Tumor Activity
Tumor response refers to the best response prior to failure (disease progression, death or second malignancy).
Time frame: Up to 6 years
Population: Efficacy data of the present study (NO18517 - NCT00532948) were pre-specified to be combined with efficacy data of the Phase 2 portion of this Study, NO21125 (NCT01118377) for analysis. Results are currently posted in the record of Study NO21125.
Secondary
Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL])
The maximum observed plasma concentration of capecitabine and its metabolites. Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline \[pre-dose\], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline \[pre-dose\], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing).
Time frame: Day 1 and Day 14
Population: The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Capecitabine (Overall) | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | 5'-DFUR, Day 1, n=2,4,3 | 1910 ng/mL | Standard Deviation 834 |
| Capecitabine (Overall) | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | 5'-DFUR, Day 14, n=2,2,2 | 3300 ng/mL | Standard Deviation 2800 |
| Capecitabine (Overall) | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | Capecitabine, Day 1, n= 2, 4, 3 | 1440 ng/mL | Standard Deviation 750 |
| Capecitabine (Overall) | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | Capecitabine, Day 14, n=2,2,2 | 2100 ng/mL | Standard Deviation 1770 |
| Capecitabine (Overall) | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | FBAL, Day 14, n=2,2,2 | 1770 ng/mL | Standard Deviation 410 |
| Capecitabine (Overall) | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | FBAL, Day 1, n=2,4,3 | 1350 ng/mL | Standard Deviation 134 |
| Capecitabine (Overall) | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | 5'-DFCR, Day 14, n=2,2,2 | 2980 ng/mL | Standard Deviation 2020 |
| Capecitabine (Overall) | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | 5'-DFCR, Day 1, n=2,4,3 | 2050 ng/mL | Standard Deviation 813 |
| Capecitabine 650 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | FBAL, Day 1, n=2,4,3 | 1740 ng/mL | Standard Deviation 365 |
| Capecitabine 650 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | Capecitabine, Day 1, n= 2, 4, 3 | 3080 ng/mL | Standard Deviation 1340 |
| Capecitabine 650 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | 5'-DFCR, Day 1, n=2,4,3 | 2190 ng/mL | Standard Deviation 626 |
| Capecitabine 650 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | 5'-DFCR, Day 14, n=2,2,2 | 3500 ng/mL | Standard Deviation 1470 |
| Capecitabine 650 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | 5'-DFUR, Day 14, n=2,2,2 | 3120 ng/mL | Standard Deviation 445 |
| Capecitabine 650 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | FBAL, Day 14, n=2,2,2 | 2430 ng/mL | Standard Deviation 84.9 |
| Capecitabine 650 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | Capecitabine, Day 14, n=2,2,2 | 5440 ng/mL | Standard Deviation 3270 |
| Capecitabine 650 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | 5'-DFUR, Day 1, n=2,4,3 | 2640 ng/mL | Standard Deviation 1700 |
| Capecitabine 850 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | 5'-DFUR, Day 14, n=2,2,2 | 5020 ng/mL | Standard Deviation 1220 |
| Capecitabine 850 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | 5'-DFCR, Day 1, n=2,4,3 | 2180 ng/mL | Standard Deviation 1690 |
| Capecitabine 850 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | Capecitabine, Day 14, n=2,2,2 | 3710 ng/mL | Standard Deviation 156 |
| Capecitabine 850 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | 5'-DFCR, Day 14, n=2,2,2 | 3200 ng/mL | Standard Deviation 233 |
| Capecitabine 850 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | Capecitabine, Day 1, n= 2, 4, 3 | 1890 ng/mL | Standard Deviation 1420 |
| Capecitabine 850 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | FBAL, Day 1, n=2,4,3 | 2050 ng/mL | Standard Deviation 1640 |
| Capecitabine 850 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | 5'-DFUR, Day 1, n=2,4,3 | 3770 ng/mL | Standard Deviation 3300 |
| Capecitabine 850 mg/m^2 | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) | FBAL, Day 14, n=2,2,2 | 2140 ng/mL | Standard Deviation 304 |
Secondary
The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
AUC last concentration of capecitabine and its metabolites. Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline \[pre-dose\], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline \[pre-dose\], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing).
Time frame: Day 1 and Day 14
Population: The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Capecitabine (Overall) | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5-FU Day 1, n=2,4,3 | 81.6 h*ng/mL | Standard Deviation 29.7 |
| Capecitabine (Overall) | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5-FU Day 14, n=2,2,2 | 181 h*ng/mL | Standard Deviation 84.7 |
| Capecitabine (Overall) | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | FBAL, Day 1, n=2,4,3 | 5990 h*ng/mL | Standard Deviation 951 |
| Capecitabine (Overall) | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | FBAL, Day 14, n=2,2,2 | 5720 h*ng/mL | Standard Deviation 690 |
| Capecitabine (Overall) | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | Capecitabine, Day 1, n= 2, 4, 3 | 3370 h*ng/mL | Standard Deviation 607 |
| Capecitabine (Overall) | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | Capecitabine, Day 14, n=2,2,2 | 2890 h*ng/mL | Standard Deviation 655 |
| Capecitabine (Overall) | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFCR, Day 1, n=2,4,3 | 5250 h*ng/mL | Standard Deviation 755 |
| Capecitabine (Overall) | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFCR, Day 14, n=2,2,2 | 4300 h*ng/mL | Standard Deviation 27.2 |
| Capecitabine (Overall) | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFUR, Day 1, n=2,4,3 | 4790 h*ng/mL | Standard Deviation 784 |
| Capecitabine (Overall) | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFUR, Day 14, n=2,2,2 | 4240 h*ng/mL | Standard Deviation 929 |
| Capecitabine 650 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | Capecitabine, Day 14, n=2,2,2 | 9660 h*ng/mL | Standard Deviation 3340 |
| Capecitabine 650 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5-FU Day 1, n=2,4,3 | 114 h*ng/mL | Standard Deviation 40.9 |
| Capecitabine 650 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFUR, Day 1, n=2,4,3 | 4300 h*ng/mL | Standard Deviation 1600 |
| Capecitabine 650 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFUR, Day 14, n=2,2,2 | 8010 h*ng/mL | Standard Deviation 1890 |
| Capecitabine 650 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5-FU Day 14, n=2,2,2 | 253 h*ng/mL | Standard Deviation 16.3 |
| Capecitabine 650 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | Capecitabine, Day 1, n= 2, 4, 3 | 5160 h*ng/mL | Standard Deviation 3700 |
| Capecitabine 650 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFCR, Day 14, n=2,2,2 | 9250 h*ng/mL | Standard Deviation 1400 |
| Capecitabine 650 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | FBAL, Day 1, n=2,4,3 | 8110 h*ng/mL | Standard Deviation 1640 |
| Capecitabine 650 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFCR, Day 1, n=2,4,3 | 5140 h*ng/mL | Standard Deviation 3440 |
| Capecitabine 650 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | FBAL, Day 14, n=2,2,2 | 10700 h*ng/mL | Standard Deviation 574 |
| Capecitabine 850 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFUR, Day 14, n=2,2,2 | 10500 h*ng/mL | Standard Deviation 445 |
| Capecitabine 850 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | FBAL, Day 14, n=2,2,2 | 10400 h*ng/mL | Standard Deviation 1760 |
| Capecitabine 850 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | Capecitabine, Day 1, n= 2, 4, 3 | 3470 h*ng/mL | Standard Deviation 1170 |
| Capecitabine 850 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFUR, Day 1, n=2,4,3 | 6650 h*ng/mL | Standard Deviation 3740 |
| Capecitabine 850 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | Capecitabine, Day 14, n=2,2,2 | 5670 h*ng/mL | Standard Deviation 971 |
| Capecitabine 850 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFCR, Day 14, n=2,2,2 | 6520 h*ng/mL | Standard Deviation 452 |
| Capecitabine 850 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFCR, Day 1, n=2,4,3 | 4180 h*ng/mL | Standard Deviation 2380 |
| Capecitabine 850 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5-FU Day 1, n=2,4,3 | 271 h*ng/mL | Standard Deviation 205 |
| Capecitabine 850 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5-FU Day 14, n=2,2,2 | 499 h*ng/mL | Standard Deviation 78.8 |
| Capecitabine 850 mg/m^2 | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | FBAL, Day 1, n=2,4,3 | 7010 h*ng/mL | Standard Deviation 4490 |
Secondary
Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
Tmax is the corresponding time at which Cmax occurs of capecitabine and its metabolites.Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline \[pre-dose\], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline \[pre-dose\], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing).
Time frame: Day 1 and Day 14
Population: The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Capecitabine (Overall) | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFUR, Day 1, n=2,4,3 | 1 Hour |
| Capecitabine (Overall) | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | FBAL, Day 14, n=2,2,2 | 1.74 Hour |
| Capecitabine (Overall) | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5-FU, Day 14, n=2,2,2 | 1.5 Hour |
| Capecitabine (Overall) | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | Capecitabine, Day 1, n= 2, 4, 3 | 0.58 Hour |
| Capecitabine (Overall) | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFCR, Day 14, n=2,2,2 | 1.49 Hour |
| Capecitabine (Overall) | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5-FU, Day 1, n=2,4,3 | 1 Hour |
| Capecitabine (Overall) | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | Capecitabine, Day 14, n=2,2,2 | 1.33 Hour |
| Capecitabine (Overall) | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFCR, Day 1, n=2,4,3 | 1.0 Hour |
| Capecitabine (Overall) | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | FBAL, Day 1, n=2,4,3 | 2.53 Hour |
| Capecitabine (Overall) | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFUR, Day 14, n=2,2,2 | 1.5 Hour |
| Capecitabine 650 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFUR, Day 14, n=2,2,2 | 0.82 Hour |
| Capecitabine 650 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFCR, Day 14, n=2,2,2 | 1.18 Hour |
| Capecitabine 650 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5-FU, Day 14, n=2,2,2 | 0.83 Hour |
| Capecitabine 650 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFUR, Day 1, n=2,4,3 | 0.9 Hour |
| Capecitabine 650 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | FBAL, Day 1, n=2,4,3 | 1.5 Hour |
| Capecitabine 650 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | FBAL, Day 14, n=2,2,2 | 2.2 Hour |
| Capecitabine 650 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | Capecitabine, Day 1, n= 2, 4, 3 | 0.63 Hour |
| Capecitabine 650 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5-FU, Day 1, n=2,4,3 | 0.75 Hour |
| Capecitabine 650 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | Capecitabine, Day 14, n=2,2,2 | 0.82 Hour |
| Capecitabine 650 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFCR, Day 1, n=2,4,3 | 0.75 Hour |
| Capecitabine 850 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | FBAL, Day 14, n=2,2,2 | 2.03 Hour |
| Capecitabine 850 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFUR, Day 14, n=2,2,2 | 0.61 Hour |
| Capecitabine 850 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5-FU, Day 1, n=2,4,3 | 1.5 Hour |
| Capecitabine 850 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5-FU, Day 14, n=2,2,2 | 1 Hour |
| Capecitabine 850 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | Capecitabine, Day 1, n= 2, 4, 3 | 0.85 Hour |
| Capecitabine 850 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | Capecitabine, Day 14, n=2,2,2 | 0.61 Hour |
| Capecitabine 850 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFCR, Day 1, n=2,4,3 | 1.55 Hour |
| Capecitabine 850 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFCR, Day 14, n=2,2,2 | 0.61 Hour |
| Capecitabine 850 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | 5'-DFUR, Day 1, n=2,4,3 | 1.5 Hour |
| Capecitabine 850 mg/m^2 | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) | FBAL, Day 1, n=2,4,3 | 1.55 Hour |