Conditions: Lung Cancer
Keywords: extensive stage small cell lung cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 671
Healthy volunteers: no

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 whether cisplatin combined with irinotecan is more effective than cisplatin combined with etoposide in treating extensive-stage small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of cisplatin combined with either irinotecan or etoposide in treating patients who have extensive-stage small cell lung cancer.

Detailed description:
OBJECTIVES:

* Compare the survival of patients with extensive stage small cell lung cancer treated with cisplatin and irinotecan vs cisplatin and etoposide.
* Compare the objective response rate and progression-free survival of patients treated with these regimens.
* Compare the toxic effects of these regimens in these patients.
* Determine the association between UGT1A1 polymorphisms and irinotecan-associated toxic effects in these patients.
* Determine the association between ERCC-1 and XRCC-1 polymorphisms and non-response of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of metastatic sites (single vs multiple), lactic dehydrogenase (no greater than upper limit of normal (ULN) vs greater than ULN), and weight loss in the past 6 months (5% or less vs more than 5%). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive irinotecan IV over 90 minutes on days 1, 8, and 15 and cisplatin IV over 30-60 minutes on day 1. Courses repeat every 4 weeks.
* Arm II: Patients receive etoposide IV over 30-60 minutes on days 1-3 and cisplatin IV over 30-60 minutes on day 1. Courses repeat every 3 weeks.

Treatment in both arms continues for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 620 patients (310 per treatment arm) will be accrued for this study within 4 years.

Arms:
arm 1: None arm 2: None

Interventions: intervention 1: cisplatin intervention 2: etoposide intervention 3: irinotecan hydrochloride
Intervention descriptions: intervention 1: Arm 1: 60 mg/m2 IV (over 30-60 min) on Day 1, Q 4 weeks x 4 Cycles

Arm 2: 80 mg/m2 IV (over 30-60 min) on Day 1, Q 4 weeks x 4 Cycles intervention 2: 100 mg/m2 IV (over 30-60 min) on Days 1 , 2 \& 3. Q 3 weeks x 4 Cycles intervention 3: 60 mg/m2 IV (over 90 min)on Days 1, 8 \& 15. Q 4 weeks x 4 Cycles

Protocol document: