Metastatic Solid Tumor
Conditions
Brief summary
The purpose of this research study is to determine the best dose of the combination of two approved drugs, intravenous topotecan and oral erlotinib.
Detailed description
The primary objectives of this trial include: * To determine the maximum tolerated dosage (MTD) of intravenous topotecan when given in combination with oral erlotinib. * To define the dosage-limiting toxicities (DLT) of this combination. * To evaluate the pharmacokinetic (PK) parameters of intravenous topotecan with and without erlotinib The secondary objectives include: * To evaluate the pharmacodynamic effect of the topotecan and erlotinib combination * To evaluate for any correlations between the presence of CYP3A4/5 polymorphisms and topotecan / erlotinib disposition and to measure the frequency of MDR1 and BCRP in peripheral blood samples and correlate these results with topotecan pharmacokinetics * To measure the frequency of UGT genotypes in peripheral blood samples * To evaluate the objective response rate using the RECIST criteria.
Interventions
DRUGTopotecan
All subjects receive treatment with intravenous topotecan and oral erlotinib.
DRUGErlotinib
All subjects receive treatment with intravenous topotecan and oral erlotinib.
Sponsors
GlaxoSmithKline
Genentech, Inc.
Accelerated Community Oncology Research Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have a histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. * Prior chemotherapy must have been completed at least 3 weeks prior to enrollment (6 weeks for nitrosureas and mitomycin) and the patient must have recovered from all associated toxicities (except alopecia and neuropathy grade 1 according to the NCI-CTC, version 3.0 classification). Radiation must have been completed 8 weeks prior to enrollment. Major surgery must have been completed 4 weeks prior to enrollment. Hormonal therapy must have been completed at least 2 weeks prior. * Age \>18 years. * ECOG performance status \<1 (Karnofsky \>70%) * Life expectancy of greater than 12 weeks. * Patients must have normal organ and marrow function as defined below: White blood cell count \>2,500/mm3, Absolute neutrophil count (ANC) \>1,500/ mm3, Platelet count \>100,000/ mm3, Hemoglobin \> 10 g/dL, Albumin \>2.5 g/dL, Total bilirubin \<1.5 X institutional upper limit of normal (ULN), AST/ALT \<1.5 X institutional ULN, Serum creatinine \<2.0 g/dL, Creatinine clearance \>40 mL/min * Patients must be able to swallow and retain oral medication * Female patients must be nonpregnant and nonlactating. All patients of childbearing potential must implement an effective method of contraception during the study. All female patients (except those who are postmenopausal or surgically sterilized) must have a negative pre-study serum or urine pregnancy test obtained within 7 days of study enrollment. * All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
Exclusion criteria
* Patients may not be receiving any other investigational agents. Participation in other clinical trials with any investigational drugs must have been completed ≥ 28 days prior to enrollment on this trial (or longer based on the halflife of the investigational agent). * Patients must have no more than 3 prior lines of therapy. The patient may have only received carboplatin and/or gemcitabine in one of the prior lines of therapy. * Patients must not be receiving concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy for cancer). Low dose maintenance steroids are acceptable if the patient will remain on a stable dose during cycles 1, 2 and 3 (to ensure continuity for topotecan pharmacokinetic studies). * Patient may not have a history of serious allergic reactions attributed to compounds of similar chemical composition to topotecan (camptothecins) and/or erlotinib (tyrosine kinase inhibitors). * Patients must not have malabsorption syndrome, any disease significantly altering gastrointestinal function, or resection of the stomach or small bowel. * Patients must not be taking warfarin (including low dose anticoagulants). * Patients must not be taking concurrent treatment with potent inhibitors of cytochrome P450 3A4. For patients who were receiving treatment with such agents, a one-week washout period is required prior to beginning the protocol. * Patients must not be taking concurrent treatment with potent inducers of cytochrome P450 3A4, such as phenytoin, carbamazepine, rifampin, barbiturates, or St. John's Wort. For patients who were receiving treatment with such agents, a one week washout period is required prior to beginning the protocol. * Patients must have no active serious infection, fever \> 38.2 degrees Celsius, or other serious underlying medical condition that would otherwise impair their ability to receive protocol treatment (i.e., documented HIV infection, uncontrolled hypertension, uncontrolled CNS metastases, unstable angina, congestive heart failure, poorly controlled diabetes, coronary angioplasty within 6 months, myocardial infarction within 6 months, uncontrolled atrial or ventricular arrhythmias). * Patients should not have psychological, familial, sociological geographical conditions that do not permit medical follow-up and compliance with the study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dosage Limiting Toxicities | DLT were assessed during the first cycle of combination topotecan and erlotinib therapy (days 1-21) | — |
| Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Renal Clearance) | Day 1 Week 1 and Day 1 Week 3 | — |
| Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Dose-Normalized AUC) | Day 1 Week 1 and Day 1 Week 3 | — |
| Maximum Tolerated Dosage (MTD) of Intravenous Topotecan When Given in Combination With Oral Erlotinib | MTD was assessed during the first cycle of combination topotecan and erlotinib therapy (days 1-21). | The MTD of topotecan was determined using a standard 3 + 3 dose escalation cohort design. The total sample and the number of patients who receive each dose in this design depends on the frequency of dose limiting toxicities (DLT) at each dosage. If 0 out of 3 patients experience a DLT at a given dosage level, 3 patients will be enrolled at the next dosage level. If greater than or equal to 2 patients experience a DLT at a given dosage level, dosage escalation will be stopped. If 1 out of 3 patients experience a DLT at a given dosage level, 3 patients are enrolled at the same dosage level. |
| Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Mean Clearance) | Day 1 Week 1 and Day 1 Week 3 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response (as Determined Using RECIST 1.0 Criteria) | Every 6 weeks until the end of study treatment | — |
| Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | Baseline | Each subgroup lists the gene on which a polymorphism occurred (e.g., CYP3A4), the name of the polymorphism (e.g., \*1), whether it was heterozygous or a variant, the number of subjects with available data, and the number who had the polymorphism. |
Countries
United States
Participant flow
Recruitment details
The study was open to enrollment at one community oncology clinic from June 2006 to November 2008.
Pre-assignment details
Informed consent was obtained from all subjects. All subjects underwent a screening period that could last up to 4 weeks during which pre-study assessments were completed. All subjects received both topotecan and erlotinib. Subjects were assigned to a Dosage Level at the time of enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group: Intravenous Topotecan and Oral Erlotinib All subjects received both topotecan and erlotinib. Subjects were assigned to a Dosage Level at the time of enrollment. Dosage level 1 was topotecan 0.75mg/m2 and erlotinib 150mg. Dosage level 2 was topotecan 1.0mg/m2 and erlotinib 150mg. Dosage level 3 was topotecan 1.25mg/m2 and erlotinib 150mg. Topotecan was administered intravenously on days 1 through 5 of each cycle. Erlotinib was administered orally daily. Cycle length was 21 days. | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | Treatment Group: Intravenous Topotecan and Oral Erlotinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Age Continuous | 58.5 years STANDARD_DEVIATION 10.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 29 |
| serious Total, serious adverse events | 11 / 29 |
Outcome results
Primary
Dosage Limiting Toxicities
Time frame: DLT were assessed during the first cycle of combination topotecan and erlotinib therapy (days 1-21)
Population: DLT were assessed using NCI CTCAE version 3.0. After MTD was determined, 13 additional patients were enrolled to enhance estimation of PK parameters. The first 8 were enrolled at dose 2. Because 4 of these patients experienced a DLT, the remaining 5 patients were enrolled at dose level 1. Of these, 1 experienced a DLT.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Dosage Limiting Toxicities | Dose Level 1 (N = 8) | 1 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Dosage Limiting Toxicities | Dose Level 2 (N = 14) | 5 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Dosage Limiting Toxicities | Dose Level 3 (N = 6) | 2 Participants |
Primary
Maximum Tolerated Dosage (MTD) of Intravenous Topotecan When Given in Combination With Oral Erlotinib
The MTD of topotecan was determined using a standard 3 + 3 dose escalation cohort design. The total sample and the number of patients who receive each dose in this design depends on the frequency of dose limiting toxicities (DLT) at each dosage. If 0 out of 3 patients experience a DLT at a given dosage level, 3 patients will be enrolled at the next dosage level. If greater than or equal to 2 patients experience a DLT at a given dosage level, dosage escalation will be stopped. If 1 out of 3 patients experience a DLT at a given dosage level, 3 patients are enrolled at the same dosage level.
Time frame: MTD was assessed during the first cycle of combination topotecan and erlotinib therapy (days 1-21).
Population: DLT information was available for 3 patients who received a topotecan dose of 0.75 mg/M\^2, for 6 patients who received a topotecan dose of 1.0 mg/M\^2, and for 6 patients who recived a topotecan dose of 1.25 mg/M\^2. 1 additional patient received a dose 1.0 mg/M\^2 but withdrew before completing cycle 1. This patient had no DLT and was replaced.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Maximum Tolerated Dosage (MTD) of Intravenous Topotecan When Given in Combination With Oral Erlotinib | 1.0 mg/m^2 |
Primary
Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Dose-Normalized AUC)
Time frame: Day 1 Week 1 and Day 1 Week 3
Population: Of the 29 consenting patients, 18 provided information that could be used in the analysis. 1 patient withdrew, 2 had samples that were inevaluable due to lab error, and 8 went off study before receiving topotecan with erlotinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Dose-Normalized AUC) | Without Erlotinib | 91.8 ng*h/mL | Standard Deviation 24.1 |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Dose-Normalized AUC) | With Erlotinib | 99.1 ng*h/mL | Standard Deviation 42.2 |
Primary
Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Mean Clearance)
Time frame: Day 1 Week 1 and Day 1 Week 3
Population: Of the 29 consenting patients, 18 provided information that could be used in the analysis. 1 patient withdrew, 2 had samples that were inevaluable due to lab error, and 8 went off study before receiving topotecan with erlotinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Mean Clearance) | Without Erlotinib | 9.41 L/h/m^2 | Standard Deviation 3.4 |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Mean Clearance) | With Erlotinib | 8.60 L/h/m^2 | Standard Deviation 3.04 |
Primary
Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Renal Clearance)
Time frame: Day 1 Week 1 and Day 1 Week 3
Population: Of the 29 consenting patients, 18 provided information that could be used in the analysis. However, only 13 were able to be analyzed for the renal clearance because in 5 patients the amount of topotecan measured in the urine was more than the topotecan dose that was given. Renal clearance was not calculated for those patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Renal Clearance) | Without Erlotinib | 4.95 L/h/m^2 | Standard Deviation 2.38 |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Renal Clearance) | With Erlotinib | 4.07 L/h/m^2 | Standard Deviation 1.87 |
Secondary
Objective Response (as Determined Using RECIST 1.0 Criteria)
Time frame: Every 6 weeks until the end of study treatment
Population: After the determination of MTD, an additional 13 patients were enrolled to enhance estimation of PK parameters. The first 8 patients were enrolled at dose level 2, 4 of whom experienced a DLT. Thus, the remaining 5 patients were enrolled at dose 1. One of these patients experienced a DLT.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 1 (N = 8) Complete Response (CR) | 0 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 1 (N = 8) Partial Response (PR) | 0 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 1 (N = 8) Stable Disease (SD) | 3 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 1 (N = 8) Progressive Disease (PD) | 4 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 1 (N = 8) Not Evaluable (NE) | 1 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 2 (N = 14) Complete Response (CR) | 0 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 2 (N = 14) Partial Response (PR) | 1 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 2 (N = 14) Stable Disease (SD) | 5 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 2 ( N = 14) Progressive Disease (PD) | 4 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 2 ( N = 14) Not Evaluable (NE) | 4 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 3 ( N = 6) Complete Response (CR) | 0 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 3 ( N = 6) Partial Response (PR) | 1 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 3 ( N = 6) Stable Disease (SD) | 4 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 3 ( N = 6) Progressive Disease (PD) | 0 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Objective Response (as Determined Using RECIST 1.0 Criteria) | Dose Level 3 ( N = 6) Not Evaluable (NE) | 1 Participants |
Secondary
Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes)
Each subgroup lists the gene on which a polymorphism occurred (e.g., CYP3A4), the name of the polymorphism (e.g., \*1), whether it was heterozygous or a variant, the number of subjects with available data, and the number who had the polymorphism.
Time frame: Baseline
Population: Pharmacokinetic studies were done for all 29 consenting patients (one of whom later withdrew).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | CYP3A4 / *1 / Wild-type, N = (28) | 20 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | CYP3A4 / *1 / Heterozygous, N = (28) | 0 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | CYP3A4 / *1 / Variant, N = (28) | 8 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | CYP3A5 / *3 / Wild-type, N = (28) | 19 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | CYP3A5 / *3 / Heterozygous, N = (28) | 3 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | CYP3A5 / *3 / Variant, N = (28) | 6 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | CYP3A5 / *6 / Wild-type, N = (29) | 27 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | CYP3A5 / *6 / Heterozygous, N = (29) | 2 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | CYP3A5 / *6 / Variant, N = (29) | 0 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | UGT1A1 / *28 / Wild-type N = (29) | 15 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | UGT1A1 / *28 / Heterozygous, N = (29) | 14 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | UGT1A1 / *28 / Variant, N = (29) | 0 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | BCRP / 34G > A / Wild-type, N = (29) | 26 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | BCRP / 34G > A / Heterozygous, N = (29) | 3 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | BCRP / 34G > A / Variant, N = (29) | 0 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | BCRP / 421C > A / Wild-type, N = (29) | 25 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | BCRP / 421C > A / Heterozygous, N = (29) | 4 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | BCRP / 421C > A / Variant, N = (29) | 0 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | P-gp / 2677G > T / Wild-type N = (29) | 13 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | P-gp / 2677G > T / Heterozygous, N = (29) | 12 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | P-gp / 2677G > T / Variant, N = (29) | 4 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | P-gp / 3435C> T / Wild-type, N = (29) | 13 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | P-gp / 3435C> T / Heterozygous, N = (29) | 7 Participants |
| Treatment Group: Intravenous Topotecan and Oral Erlotinib | Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) | P-gp / 3435C> T / Variant, N = (29) | 9 Participants |