Extensive Stage Small Cell Lung Cancer
Conditions
Keywords
extensive stage small cell lung cancer, Topotecan, Etoposide, Cisplatin, Irinotecan
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating extensive-stage small cell lung cancer. PURPOSE: Randomized phase II trial to compare the effectiveness of two combination chemotherapy regimens in treating patients who have extensive-stage small cell lung cancer.
Detailed description
OBJECTIVES: Primary * Evaluate the response frequency of patients with extensive stage small cell lung cancer treated with topotecan, cisplatin, and etoposide and with irinotecan, cisplatin, and etoposide. * Evaluate the toxic effects of these regimens in these patients. * Evaluate the duration of response and survival of patients treated with these regimens. Secondary * To investigate the occurrence of various breast cancer resistance protein (BCRP) alleles in patients receiving topoisomerase 1 inhibitors and their impact on clinical response and toxicity. OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. * Arm I (PET): Patients receive topotecan intravenously (IV) over 30 minutes on days 1-3; etoposide IV over 60 minutes immediately followed by cisplatin IV over 60 minutes on days 8-10; and filgrastim (G-CSF) subcutaneously daily beginning on day 11 and continuing until blood counts recover. * Arm II (PIE): Patients receive irinotecan IV over 90 minutes and cisplatin IV over 60 minutes on days 1 and 8 and oral etoposide twice daily on days 3 and 10. In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 1 year. ACTUAL ACCRUAL: A total of 140 patients were accrued for this study.
Interventions
BIOLOGICALG-CSF
G-CSF will be administered subcutaneously at a dose of 5 mcg/kg once a day starting on day 11 until WBC recovery \> 10,000 dL.
DRUGCisplatin
Arm PET: 20 mg/m2 IV on days 8, 9 and 10 of each cycle following Etoposide. Arm PIE: 20 mg/m2 IV on days 1 and 8 of each cycle following Irinotecan.
DRUGEtoposide
Arm PET: 70 mg/m2 IV over 60 minutes on days 8, 9 and 10 of each cycle. Arm PIE: 85 mg/m2 orally (divided into 2 doses, 12 hours apart) on day 3 and 10 of each cycle.
DRUGIrinotecan
50 mg/m2 IV over 90 minutes on days 1 and 8 of each cycle (Arm PIE only).
DRUGTopotecan
Topotecan 0.75 mg/m2 IV over 30 minutes on days 1,2 and 3 of each cycle (Arm PET only).
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Extensive stage small cell lung cancer (SCLC) with measurable disease, evaluated within 2 weeks prior to randomization * Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 * Disease-free for \>=5 years if had a prior second malignancy other than treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix * Adequate hematologic, hepatic and renal function determined by the following tests, within 4 weeks prior to randomization: white blood cell (WBC) \>=4000/mm3 and platelets \>=100,000/mm3; bilirubin \<= upper limit of normal; serum glutamic pyruvate transaminase (SGPT) or alanine transaminase (ALT) and serum glutamic oxaloacetic transaminase (SGOT) or aspartate transaminase( AST) \<=2.5 x upper limit of normal if no demonstrable liver metastases or \<=5 times upper limit of normal in the presence of liver metastases; Calculated creatinine clearance \>=30 using the formulas in the protocol * Age 18 and older * Strongly advised to use an accepted and effective method of contraception * Those with central nervous system (CNS) metastases were eligible if the metastases were treated without advancing symptoms prior to the initiation of chemotherapy * Those receiving erythropoietin could continue to receive it
Exclusion criteria
* Prior radiotherapy for lung cancer; Prior radiotherapy allowed only for central nervous system (CNS) metastases * Prior chemotherapy for this disease * Pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Objective Response by Solid Tumor Response Criteria (RECIST) | Assessed every 6 weeks while on treatment, and then every 3 months for patients < 2 years from study entry, every 6 months if patient is 2-3 years from study entry. | Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= \>=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | Assessed every 6 weeks while on treatment, and then every 3 months for patients < 2 years from study entry, every 6 months if patient is 2-3 years from study entry. | Duration of response is defined as the period measured from the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the first date that recurrent or progressive disease is objectively documented, taking as reference the smallest measurements recorded since treatment started. |
| Overall Survival | Assessed every 3 months for 2 years, then every 6 months for 1 years | Overall survival is defined as the time from randomization to death. |
Countries
United States
Participant flow
Recruitment details
The study opened to accrual on March 24, 2004, accrued its first patient on July 14, 2004, and was closed on April 14, 2008 with final accrual of 140 patients.
Participants by arm
| Arm | Count |
|---|---|
| PET (Topotecan/Etoposide/Cisplatin/G-CSF) Patients receive topotecan intravenously (IV) over 30 minutes on days 1-3; etoposide IV over 60 minutes immediately followed by cisplatin IV over 60 minutes on days 8-10; and filgrastim (G-CSF) subcutaneously daily beginning on day 11 and continuing until blood counts recover. | 66 |
| PIE (Irinotecan/Cisplatin/Etoposide) Patients receive irinotecan IV over 90 minutes and cisplatin IV over 60 minutes on days 1 and 8 and oral etoposide twice daily on days 3 and 10 of each cycle. | 66 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 12 |
| Overall Study | Alternative therapy | 0 | 1 |
| Overall Study | Death | 5 | 4 |
| Overall Study | Ineligible | 3 | 3 |
| Overall Study | Never started treatment | 1 | 1 |
| Overall Study | Other complicating disease | 2 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Progression/relapse | 12 | 14 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | PET (Topotecan/Etoposide/Cisplatin/G-CSF) | PIE (Irinotecan/Cisplatin/Etoposide) | Total |
|---|---|---|---|
| Age, Continuous | 60 years | 64 years | 63 years |
| Sex: Female, Male Female | 25 Participants | 33 Participants | 58 Participants |
| Sex: Female, Male Male | 41 Participants | 33 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 66 / 69 | 67 / 68 |
| serious Total, serious adverse events | 48 / 69 | 51 / 68 |
Outcome results
Primary
Proportion of Patients With Objective Response by Solid Tumor Response Criteria (RECIST)
Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= \>=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR
Time frame: Assessed every 6 weeks while on treatment, and then every 3 months for patients < 2 years from study entry, every 6 months if patient is 2-3 years from study entry.
Population: Only treated and eligible patients are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PET (Topotecan/Etoposide/Cisplatin/G-CSF) | Proportion of Patients With Objective Response by Solid Tumor Response Criteria (RECIST) | 0.697 proportion of participants |
| PIE (Irinotecan/Cisplatin/Etoposide) | Proportion of Patients With Objective Response by Solid Tumor Response Criteria (RECIST) | 0.576 proportion of participants |
Secondary
Duration of Response
Duration of response is defined as the period measured from the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the first date that recurrent or progressive disease is objectively documented, taking as reference the smallest measurements recorded since treatment started.
Time frame: Assessed every 6 weeks while on treatment, and then every 3 months for patients < 2 years from study entry, every 6 months if patient is 2-3 years from study entry.
Population: Only eligible and treated patients with response are included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PET (Topotecan/Etoposide/Cisplatin/G-CSF) | Duration of Response | 6.0 Months |
| PIE (Irinotecan/Cisplatin/Etoposide) | Duration of Response | 6.0 Months |
Secondary
Overall Survival
Overall survival is defined as the time from randomization to death.
Time frame: Assessed every 3 months for 2 years, then every 6 months for 1 years
Population: Only eligible and treated patients are included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PET (Topotecan/Etoposide/Cisplatin/G-CSF) | Overall Survival | 11.9 Months |
| PIE (Irinotecan/Cisplatin/Etoposide) | Overall Survival | 11.0 Months |