Colorectal Cancer, Neurotoxicity
Conditions
Keywords
neurotoxicity, stage II colon cancer, stage III colon cancer, adenocarcinoma of the colon, stage II rectal cancer, stage III rectal cancer, stage IV rectal cancer, stage IV colon cancer, adenocarcinoma of the rectum
Brief summary
RATIONALE: Calcium gluconate and magnesium sulfate may prevent or lessen neurotoxicity caused by oxaliplatin. It is not yet known whether calcium gluconate and magnesium sulfate are more effective than a placebo in preventing neurotoxicity caused by oxaliplatin in patients receiving combination chemotherapy. PURPOSE: This randomized phase III trial is studying calcium gluconate and magnesium sulfate to see how well they work compared to a placebo in preventing neurotoxicity caused by oxaliplatin in patients receiving combination chemotherapy for stage II, stage III, or stage IV colorectal cancer that has been completely removed by surgery.
Detailed description
OBJECTIVES: * Determine whether calcium gluconate and magnesium sulfate (CaMg) infusions can prevent or ameliorate chronic, cumulative oxaliplatin-induced neurotoxicity in patients receiving FOLFOX combination chemotherapy for stage II, III or IV colorectal cancer. * Determine whether CaMg infusions can increase the cumulative oxaliplatin doses that can be delivered without chronic neurotoxicity. * Determine whether CaMg infusions can ameliorate the acute neuropathy associated with oxaliplatin. * Determine whether CaMg infusions cause any adverse events. * Investigate whether CaMg infusions influence quality of life, fatigue, and activities of daily living of these patients. * Determine if polymorphisms in the GSTP1 gene predict early onset of oxaliplatin-induced neurotoxicity. OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to age (\< 65 vs \> 65), gender, and chemotherapy regimen (FOLFOX4 vs modified FOLFOX6). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after each oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen. * Arm II: Patients receive a placebo IV over 30 minutes immediately before and after each oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen. In both arms, treatment continues until chemotherapy is discontinued (approximately 6 months). Patients complete quality of life questionnaires on day 1, a symptom experience diary on days 2-5 of their chemotherapy regimen, and questionnaires at 1 and 3 months after completion of study treatment. Blood samples are collected at baseline and tested for the GSTP1 gene. After completion of study treatment, patients are followed for at least 3 months. PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.
Interventions
Sponsors
National Cancer Institute (NCI)
North Central Cancer Treatment Group
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the colon or rectum * Stage II disease * Stage III disease * Stage IV disease (completely resected with no evidence of residual tumor) * Must have undergone curative resection for stage II or III disease * Scheduled to receive 6 months of adjuvant treatment with either of the following FOLFOX chemotherapy regimens: * FOLFOX4, comprising leucovorin calcium, fluorouracil, and oxaliplatin (2-week course) * Modified FOLFOX6, comprising high-dose leucovorin calcium, high-dose fluorouracil, and oxaliplatin (2-week course) PATIENT CHARACTERISTICS: * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 10 g/dL * WBC ≥ 3,000/mm\^3 * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * Creatinine ≤ 1.5 times ULN * Calcium normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No pre-existing peripheral neuropathy of any grade * No hypercalcemia * No concurrent heart block or a history of heart block * No other medical condition that, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient * No family history of a genetic/familial neuropathy PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior treatment with neurotoxic chemotherapy such as oxaliplatin, cisplatin, taxanes, or vinca alkaloids * Concurrent use of bevacizumab or cetuximab in combination with FOLFOX as part of a clinical trial or clinical practice are allowed * No concurrent digitalis medication * No concurrent digoxin * No concurrent treatment with anticonvulsants such as carbamazepine, phenytoin, or valproic acid * No other concurrent neurotropic agents such as gabapentin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Oxaliplatin-induced Grade 2+ Chronic Neuropathic Adverse Event | 127 days | Neuropathic adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Neurotoxicity evaluation grade: loss of deep tendon reflexes or paresthesia, including tingling, but not interfering with function (Grade 1); objective sensory alteration or paresthesia, including tingling, interfering with function, but not with activities of daily living (Grade 2); sensory alteration or paresthesia interfering with activities of daily living (Grade 3); permanent sensory losses that are disabling (Grade 4) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Grade 2+ Chronic Neurotoxicity | 127 days | Neurotoxicity were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. |
| Time to Onset of Grade 3+ Chronic Neurotoxicity | 127 days | Neurotoxicity was assessed by CTCAE v3.0. |
| Average Duration of Chronic Neuropathic Toxicity | 127 days | Neuropathic adverse events were assessed by CTCAE v3.0. |
| Percentage of Patients Discontinuing Therapy for Chronic Neurotoxicity | 127 days | Neurotoxicity were assessed by CTCAE v3.0. |
| Average Cumulative Oxaliplatin Dose | 127 days | — |
| Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | 127 days | Adverse Events were measured using CTCAE V3.0. |
| Percentage of Patients With Acute Neuropathic Adverse Event | 127 days | Acute neuropathic toxicities were measured using the Symptom Experience Diary and supplemental quality of life questions in the scale of 0 (no symptom) to 10 (worst symptom). The item score was reversed and transformed into 0 (low QOL) to 100 (best QOL) scale for analysis. Any score greater than 0 was considered having acute neuropathy. |
| Percentage of Patients Experiencing Impact on Activities of Daily Living (ADL) | 127 days | Activities of daily living were measured using the Symptom Experience Diary and supplemental quality of life questions. The questionnaires' items were in the scale of 0 (no symptom) to 10 (worst symptom). |
| Change From Baseline in Fatigue Score at One Month | Baseline and One month | Fatigue was measured by Brief Fatigue Inventory in the scale of 0 (no fatigue) to 10 (fatigue as bad as you can imagine). The item score was reversed and transformed into 0 (low quality of life (QOL)) to 100 (best QOL) scale for analysis. Change: score at one month minus score at baseline. |
| Change From Baseline in Quality of Life (QOL) at One Month | Baseline and One month | Quality of Life (QOL) were measured using the Symptom Experience Diary and supplemental quality of life questions. Item score range: 0 (no symptom) to 10 (worst symptom). The score was reversed and transformed into 0 (low QOL) to 100 (best QOL) scale for analysis. Change: score at one month minus score at baseline. |
| Average Duration of Oxaliplatin-containing Treatment | 127 days | — |
Countries
United States
Participant flow
Recruitment details
One-hundred and four (104) participants were recruited between January 2006 and June 2007 from 20 North Central Cancer Treatment Group (NCCTG) member sites.
Pre-assignment details
Two participants in Calcium/Magnesium arm canceled prior to study medication begins. These two participants were excluded from all analysis.
Participants by arm
| Arm | Count |
|---|---|
| Ca/Mg Patients receive calcium gluconate (Ca) and magnesium sulfate (Mg) IV over 30 minutes immediately before and after each oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen. | 50 |
| Placebo Patients receive a placebo IV over 30 minutes immediately before and after each oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen. | 52 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 7 |
| Overall Study | Missing end of treatment documentation | 14 | 15 |
| Overall Study | Other Problems | 6 | 11 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Ca/Mg | Placebo | Total |
|---|---|---|---|
| Age, Customized <65 | 33 Participants | 33 Participants | 66 Participants |
| Age, Customized >=65 | 17 Participants | 19 Participants | 36 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 48 Participants | 50 Participants | 98 Participants |
| Regimen FOLFOX4 (Oxaliplatin, Leucovorin, and Fluorouracil | 3 Participants | 3 Participants | 6 Participants |
| Regimen Modified FOLFOX6 | 47 Participants | 49 Participants | 96 Participants |
| Region of Enrollment United States | 50 participants | 52 participants | 102 participants |
| Sex: Female, Male Female | 23 Participants | 25 Participants | 48 Participants |
| Sex: Female, Male Male | 27 Participants | 27 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 48 / 50 | 46 / 52 |
| serious Total, serious adverse events | 2 / 50 | 1 / 52 |
Outcome results
Primary
Percentage of Patients With Oxaliplatin-induced Grade 2+ Chronic Neuropathic Adverse Event
Neuropathic adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Neurotoxicity evaluation grade: loss of deep tendon reflexes or paresthesia, including tingling, but not interfering with function (Grade 1); objective sensory alteration or paresthesia, including tingling, interfering with function, but not with activities of daily living (Grade 2); sensory alteration or paresthesia interfering with activities of daily living (Grade 3); permanent sensory losses that are disabling (Grade 4)
Time frame: 127 days
Population: Efficacy analyses use all patients that reported at least one value after baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ca/Mg | Percentage of Patients With Oxaliplatin-induced Grade 2+ Chronic Neuropathic Adverse Event | 22 Percentage of participants |
| Placebo | Percentage of Patients With Oxaliplatin-induced Grade 2+ Chronic Neuropathic Adverse Event | 41 Percentage of participants |
Comparison: Comparison in Percentage of Patients With Oxaliplatin-induced Grade 2+ Chronic Neuropathic Adverse Event between Armsp-value: 0.038Chi-squared
Secondary
Average Cumulative Oxaliplatin Dose
Time frame: 127 days
Population: Because of the early closure of this trial, no reliable data were available for this outcome.
Secondary
Average Duration of Chronic Neuropathic Toxicity
Neuropathic adverse events were assessed by CTCAE v3.0.
Time frame: 127 days
Population: Includes all patients that reported at least one value after baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ca/Mg | Average Duration of Chronic Neuropathic Toxicity | 81 days |
| Placebo | Average Duration of Chronic Neuropathic Toxicity | 72 days |
Comparison: Comparison of Average Duration of Chronic Neuropathic Toxicity between Armsp-value: 0.6556Log Rank
Secondary
Average Duration of Oxaliplatin-containing Treatment
Time frame: 127 days
Population: Because of the early closure of this trial, no reliable data were available for this outcome.
Secondary
Change From Baseline in Fatigue Score at One Month
Fatigue was measured by Brief Fatigue Inventory in the scale of 0 (no fatigue) to 10 (fatigue as bad as you can imagine). The item score was reversed and transformed into 0 (low quality of life (QOL)) to 100 (best QOL) scale for analysis. Change: score at one month minus score at baseline.
Time frame: Baseline and One month
Population: Includes all patients with at least one assessment after baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ca/Mg | Change From Baseline in Fatigue Score at One Month | Fatigue NOW | 1.0 units on a scale | Standard Deviation 14.96 |
| Ca/Mg | Change From Baseline in Fatigue Score at One Month | Fatigue USUAL | 3.1 units on a scale | Standard Deviation 15.38 |
| Ca/Mg | Change From Baseline in Fatigue Score at One Month | Fatigue WORST | 0.0 units on a scale | Standard Deviation 21.38 |
| Placebo | Change From Baseline in Fatigue Score at One Month | Fatigue NOW | -2.8 units on a scale | Standard Deviation 17.92 |
| Placebo | Change From Baseline in Fatigue Score at One Month | Fatigue USUAL | -1.6 units on a scale | Standard Deviation 12.81 |
| Placebo | Change From Baseline in Fatigue Score at One Month | Fatigue WORST | -1.6 units on a scale | Standard Deviation 18.41 |
Comparison: Comparison of Fatigue NOW between two armsp-value: 0.234Kruskal-Wallis
Comparison: Comparison of Fatigue USUAL between two armsp-value: 0.201Kruskal-Wallis
Comparison: Comparison of Fatigue WORST between two armsp-value: 0.9364Kruskal-Wallis
Secondary
Change From Baseline in Quality of Life (QOL) at One Month
Quality of Life (QOL) were measured using the Symptom Experience Diary and supplemental quality of life questions. Item score range: 0 (no symptom) to 10 (worst symptom). The score was reversed and transformed into 0 (low QOL) to 100 (best QOL) scale for analysis. Change: score at one month minus score at baseline.
Time frame: Baseline and One month
Population: Includes all patients with at least one assessment after baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ca/Mg | Change From Baseline in Quality of Life (QOL) at One Month | Diarrhea | -7.1 Units on a scale | Standard Deviation 18.43 |
| Ca/Mg | Change From Baseline in Quality of Life (QOL) at One Month | Bowel Problems with Normal Activity | -3.2 Units on a scale | Standard Deviation 18.06 |
| Ca/Mg | Change From Baseline in Quality of Life (QOL) at One Month | Buttoning Shirt or Tying Laces | -2.0 Units on a scale | Standard Deviation 9.27 |
| Ca/Mg | Change From Baseline in Quality of Life (QOL) at One Month | Shortness of Breath (Week 2 - Baseline) | -0.7 Units on a scale | Standard Deviation 7.16 |
| Ca/Mg | Change From Baseline in Quality of Life (QOL) at One Month | Constipation | -2.9 Units on a scale | Standard Deviation 14.87 |
| Ca/Mg | Change From Baseline in Quality of Life (QOL) at One Month | Swallowing (Week 2 - Baseline) | -7.5 Units on a scale | Standard Deviation 17.56 |
| Ca/Mg | Change From Baseline in Quality of Life (QOL) at One Month | Walking | -2.5 Units on a scale | Standard Deviation 11.54 |
| Ca/Mg | Change From Baseline in Quality of Life (QOL) at One Month | Numbness in Fingers, Toes (Week 2 - Baseline) | -8.3 Units on a scale | Standard Deviation 16.49 |
| Ca/Mg | Change From Baseline in Quality of Life (QOL) at One Month | Abdominal Cramping | -2.5 Units on a scale | Standard Deviation 11.75 |
| Ca/Mg | Change From Baseline in Quality of Life (QOL) at One Month | Tingling in Fingers, Toes (Week 2 - Baseline) | -14.8 Units on a scale | Standard Deviation 21.65 |
| Ca/Mg | Change From Baseline in Quality of Life (QOL) at One Month | Fatigue WORST | 0.0 Units on a scale | Standard Deviation 21.38 |
| Placebo | Change From Baseline in Quality of Life (QOL) at One Month | Tingling in Fingers, Toes (Week 2 - Baseline) | -20.4 Units on a scale | Standard Deviation 20.53 |
| Placebo | Change From Baseline in Quality of Life (QOL) at One Month | Fatigue WORST | -1.6 Units on a scale | Standard Deviation 18.41 |
| Placebo | Change From Baseline in Quality of Life (QOL) at One Month | Walking | 0.2 Units on a scale | Standard Deviation 12.78 |
| Placebo | Change From Baseline in Quality of Life (QOL) at One Month | Buttoning Shirt or Tying Laces | 0.4 Units on a scale | Standard Deviation 21.07 |
| Placebo | Change From Baseline in Quality of Life (QOL) at One Month | Diarrhea | -10.4 Units on a scale | Standard Deviation 21.77 |
| Placebo | Change From Baseline in Quality of Life (QOL) at One Month | Constipation | 0.4 Units on a scale | Standard Deviation 26.94 |
| Placebo | Change From Baseline in Quality of Life (QOL) at One Month | Abdominal Cramping | 1.3 Units on a scale | Standard Deviation 23.46 |
| Placebo | Change From Baseline in Quality of Life (QOL) at One Month | Bowel Problems with Normal Activity | -9.1 Units on a scale | Standard Deviation 19.05 |
| Placebo | Change From Baseline in Quality of Life (QOL) at One Month | Shortness of Breath (Week 2 - Baseline) | 2.1 Units on a scale | Standard Deviation 22.26 |
| Placebo | Change From Baseline in Quality of Life (QOL) at One Month | Swallowing (Week 2 - Baseline) | 2.1 Units on a scale | Standard Deviation 21.87 |
| Placebo | Change From Baseline in Quality of Life (QOL) at One Month | Numbness in Fingers, Toes (Week 2 - Baseline) | -9.6 Units on a scale | Standard Deviation 15.74 |
Comparison: Fatigue WORSTp-value: 0.9364Kruskal-Wallis
Comparison: Walkingp-value: 0.6275Kruskal-Wallis
Comparison: Buttoning Shirt or Tying Lacesp-value: 0.6988Kruskal-Wallis
Comparison: Diarrheap-value: 0.5124Kruskal-Wallis
Comparison: Constipationp-value: 0.3103Kruskal-Wallis
Comparison: Abdominal Crampingp-value: 0.8601Kruskal-Wallis
Comparison: Bowel Problems with Normal Activityp-value: 0.2439Kruskal-Wallis
Comparison: Shortness of Breath (Week 2 - Baseline)p-value: 0.9283Kruskal-Wallis
Comparison: Swallowing (Week 2 - Baseline)p-value: 0.4715Kruskal-Wallis
Comparison: Numbness in Fingers, Toes (Week 2 - Baseline)p-value: 0.5105Kruskal-Wallis
Comparison: Tingling in Fingers, Toes (Week 2 - Baseline)p-value: 0.2181Kruskal-Wallis
Secondary
Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event
Adverse Events were measured using CTCAE V3.0.
Time frame: 127 days
Population: Analyses of adverse events includes all patients. Adverse event data is not available on one patient in Placebo arm, which leads to the total of 51 in Placebo arm for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Laryngeal Discomfort | 0 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Fatigue | 10 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Leukopenia | 6 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Constipation | 42 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Muscle Weakness | 2 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Hypercalcemia | 0 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Myalgia | 4 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Acne NOS | 2 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Nausea | 60 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Hyperglycemia | 2 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Neuro-motor | 4 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Dehydration | 2 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Neuro-sensory | 2 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Hypermagnesemia | 14 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Neutropenia | 18 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Anorexia | 4 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Oral cavity MS CE | 2 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Hypersensitivity | 6 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Pain-Abdominal | 0 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Hypokalemia | 4 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Pain-Chest | 0 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Diarrhea-No Colostom | 68 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Pain-Headache | 0 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Hypomagnesemia | 0 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Rash/Desquamation | 4 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Abdominal Infection | 2 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Skin Rxn-Hand/Foot | 4 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Hyponatremia | 4 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Stomatitis | 2 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Dry Skin | 0 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Taste | 2 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Infection | 0 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Thrombocytopenia | 2 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Clostridial Infection | 0 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Thrombosis | 6 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Ischemia-Cerebral | 0 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Urticaria | 0 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Erythema Multiforme | 4 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Vasc Access Complication | 2 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Ischemia/Infarction | 2 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Vomiting | 34 Percentage of Participants |
| Ca/Mg | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Anemia | 4 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Vomiting | 33 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Abdominal Infection | 0 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Acne NOS | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Anemia | 4 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Anorexia | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Clostridial Infection | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Constipation | 47 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Dehydration | 6 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Diarrhea-No Colostom | 73 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Dry Skin | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Erythema Multiforme | 0 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Fatigue | 25 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Hypercalcemia | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Hyperglycemia | 0 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Hypermagnesemia | 18 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Hypokalemia | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Hypomagnesemia | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Hyponatremia | 0 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Infection | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Ischemia-Cerebral | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Ischemia/Infarction | 0 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Laryngeal Discomfort | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Leukopenia | 10 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Muscle Weakness | 0 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Myalgia | 0 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Nausea | 71 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Neuro-motor | 4 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Neuro-sensory | 12 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Neutropenia | 33 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Oral cavity MS CE | 0 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Pain-Abdominal | 8 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Pain-Chest | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Pain-Headache | 4 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Rash/Desquamation | 0 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Skin Rxn-Hand/Foot | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Stomatitis | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Taste | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Thrombocytopenia | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Thrombosis | 4 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Urticaria | 2 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Vasc Access Complication | 0 Percentage of Participants |
| Placebo | Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event | Hypersensitivity | 0 Percentage of Participants |
Secondary
Percentage of Patients Discontinuing Therapy for Chronic Neurotoxicity
Neurotoxicity were assessed by CTCAE v3.0.
Time frame: 127 days
Population: Includes all patients that reported at least one value after baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ca/Mg | Percentage of Patients Discontinuing Therapy for Chronic Neurotoxicity | 46 Percentage of Participants |
| Placebo | Percentage of Patients Discontinuing Therapy for Chronic Neurotoxicity | 55.8 Percentage of Participants |
Comparison: Comparison of Percentage of patients discontinuing therapy for chronic neurotoxicity between Armsp-value: 0.3238Chi-squared
Secondary
Percentage of Patients Experiencing Impact on Activities of Daily Living (ADL)
Activities of daily living were measured using the Symptom Experience Diary and supplemental quality of life questions. The questionnaires' items were in the scale of 0 (no symptom) to 10 (worst symptom).
Time frame: 127 days
Population: Data was collected but not analyzed for this outcome.
Secondary
Percentage of Patients With Acute Neuropathic Adverse Event
Acute neuropathic toxicities were measured using the Symptom Experience Diary and supplemental quality of life questions in the scale of 0 (no symptom) to 10 (worst symptom). The item score was reversed and transformed into 0 (low QOL) to 100 (best QOL) scale for analysis. Any score greater than 0 was considered having acute neuropathy.
Time frame: 127 days
Population: Includes all patients that reported at least one value after baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ca/Mg | Percentage of Patients With Acute Neuropathic Adverse Event | 88 Percentage of participants |
| Placebo | Percentage of Patients With Acute Neuropathic Adverse Event | 90 Percentage of participants |
Comparison: Comparison of Percentage of Patients With Acute Neuropathic Adverse Event between Armsp-value: 0.7498Chi-squared
Secondary
Time to Onset of Grade 2+ Chronic Neurotoxicity
Neurotoxicity were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0.
Time frame: 127 days
Population: Includes all patients that reported at least one value after baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ca/Mg | Time to Onset of Grade 2+ Chronic Neurotoxicity | NA Days |
| Placebo | Time to Onset of Grade 2+ Chronic Neurotoxicity | 18.1 Days |
Comparison: Comparison of time to Onset of Grade 2+ Chronic Neurotoxicity between Armsp-value: 0.0503Log Rank
Secondary
Time to Onset of Grade 3+ Chronic Neurotoxicity
Neurotoxicity was assessed by CTCAE v3.0.
Time frame: 127 days
Population: Includes all patients that reported at least one value after baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ca/Mg | Time to Onset of Grade 3+ Chronic Neurotoxicity | NA Days |
| Placebo | Time to Onset of Grade 3+ Chronic Neurotoxicity | NA Days |
Comparison: Comparison of Time to Onset of Grade 3+ Chronic Neurotoxicity between Armsp-value: 0.4048Log Rank