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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
Overall Survival
Overall survival was defined as the duration between the date of randomization( enrollment) and the date of death due to any cause. Patients last known to be alive were censored at the date of last contact.
Time frame: Weekly while on treatment, then every 3 months for first year, then every 6 months unitl a maximum of 3 years from enrollment.
Progression-free Survival
Progression-Free Survival was defined as the duration from the date of randomization (enrollment) until the date of documentation of progression as defined by RECIST (a 20% increase over nadir in the sum of longest diameters of target lesions, clear progression of a non-target lesion in the opinion of the treating investigator, appearance of new lesions, or symptomatic deterioration) or death due to any cause. Patients last known to be alive and without evidence of progression were censored at the date of last contact.
Time frame: Every 6 weeks until disease progression or a maximum of 3 years from the date of enrollment.
Confirmed and Unconfirmed Complete and Partial Responses.
Patients underwent chest CT/MRI every 6 weeks while on treatment and tumor response was evaluated by RECIST in the subset of patients with at least one target lesion at baseline. A target lesion was defined as a lesion with a longest diameter of at least 2 cm ( or at least 1 cm if by spiral CT). A complete response (CR) was defined as the disappearance of all disease, including non-target lesions. A partial response (PR) was defined as a 30% or greater decrease in the sum of the longest diameters. Confirmation of a CR or PR was defined as a second determination of CR or PR at least 4 weeks after the first determination.
Time frame: Every 6 weeks while on protocol treatment for a maximum of 12 weeks
Number of Patients With a Given Type and Grade of Adverse Event.
Only adverse events that are possibly, probably or definitely related to study drug are reported. Only patients who received protocol treatment and were assessed for adverse events are included.
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NONE
Enrollment
671
Northeast Alabama Regional Medical Center
Anniston, Alabama, United States
Huntsville Hospital
Huntsville, Alabama, United States
Mobile Infirmary Medical Center
Mobile, Alabama, United States
East Alabama Medical Center
Opelika, Alabama, United States
Alaska Regional Hospital Cancer Center
Anchorage, Alaska, United States
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States
Arizona Cancer Center at University of Arizona Health Sciences Center
Tucson, Arizona, United States
Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
Fort Smith, Arkansas, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Providence Saint Joseph Medical Center - Burbank
Burbank, California, United States
...and 398 more locations
Time frame: Every 4 weeks while subject on protocol treatment for a maximum of 12 weeks.