Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Extensive-Stage Small Cell Lung Cancer

Eastern Cooperative Oncology Group

Status and phase: Completed; Phase 2

Conditions: Extensive Stage Small Cell Lung Cancer

Treatments: Biological: G-CSF; Drug: Cisplatin; Drug: Etoposide; Drug: Topotecan; Drug: Irinotecan

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00057837

E5501 (Other Identifier)

CDR0000276590

U10CA021115 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 140 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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140 participants in 2 patient groups

PET (Topotecan/Etoposide/Cisplatin/G-CSF)

Experimental group

Description:

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.

Treatment:

Drug: Topotecan

Biological: G-CSF

Drug: Etoposide

Drug: Cisplatin

PIE (Irinotecan/Cisplatin/Etoposide)

Experimental group

Description:

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.

Treatment:

Drug: Irinotecan

Drug: Etoposide

Drug: Cisplatin