Phase II Study of Sequential Topotecan-Carboplatin-Etoposide in Patients With Extensive Stage Small Cell Lung Cancer

OBJECTIVES:

• Determine the toxicity profile and maximum tolerated dose of sequential topotecan, carboplatin, and etoposide in patients with chemotherapy-naive extensive stage small cell lung cancer. (Phase I closed to accrual as of 04/04/2003).
• Determine the response rate and duration of response in patients with treated with this regimen.
• Determine the failure-free and overall survival of patients treated with this regimen.
• Determine the pharmacokinetics and pharmacodynamics of topotecan and etoposide on this schedule in these patients.

OUTLINE: This is a dose-escalation, multicenter study of topotecan and etoposide. (Phase I closed to accrual as of 04/04/2003).

Patients receive oral topotecan on days 1-5, carboplatin IV over 30 minutes on day 6, and oral etoposide on days 6-10. Treatment continues every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with complete response (CR) or partial response after the second course receive up to 4 additional courses. Patients with brain metastases at initial presentation undergo whole-brain irradiation before the chemotherapy regimen. Patients without brain metastases at initial presentation who achieve CR undergo prophylactic whole-brain irradiation.

Sequential dose escalation of topotecan is followed by sequential dose escalation of etoposide. Cohorts of 3-6 patients receive escalating doses of topotecan and then etoposide until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. (Phase I closed to accrual as of 04/04/2003). In the phase II part of study, an additional 11-40 patients are accrued to receive topotecan, carboplatin, and etoposide at the MTD.