Trial Information

Phase III Randomized Trial of Sequential High-Dose Chemotherapy Versus Standard Chemotherapy for the Treatment of Small Cell Lung Cancer

OBJECTIVES:

- Compare the overall survival of patients with limited or extensive stage small cell
lung cancer treated with sequential high-dose ifosfamide, carboplatin, and etoposide
phosphate followed by autologous peripheral blood stem cell or bone marrow
transplantation versus standard ifosfamide, carboplatin, and etoposide.

- Compare the progression-free survival, time to treatment failure, and response rate in
patients treated with these regimens.

- Compare the toxic effects of these regimens in these patients.

- Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
disease stage (limited disease vs extensive disease with vs without liver metastases),
performance status (0 vs 1), gender, LDH level (normal vs abnormal), and participating
center. Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive induction therapy comprising epirubicin IV over 4 hours on day
1 and paclitaxel IV over 3 hours on day 2. Treatment repeats every 21 days for a total
of 2 courses. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on
day 3 and continuing for 10 days or during course 2 until peripheral blood stem cell
(PBSC) collection is completed. After completion of induction chemotherapy, autologous
PBSCs or bone marrow is collected.

Within 28 days of the start of the second course of induction chemotherapy, patients receive
high-dose ifosfamide IV over 17 hours, carboplatin IV over 3 hours, and etoposide phosphate
IV over 3 hours on days 1-4. At 48 hours after completion of high-dose chemotherapy,
patients undergo autologous PBSC or bone marrow transplantation and then receive G-CSF SC
for 14 days. Treatment repeats every 28 days for 3 courses.

- Arm II: Patients receive ifosfamide IV continuously over 24 hours, carboplatin IV over
1 hour on day 1, and etoposide IV over 45 minutes on days 1 and 2. Treatment repeats
every 28 days for 6 courses.

After completion of high-dose or standard chemotherapy, patients with limited disease or
extensive disease in complete remission receive thoracic radiotherapy daily on days 1-5 for
6 weeks. All patients in complete remission receive prophylactic cranial radiotherapy daily
on days 1-5 for 3 weeks.

Quality of life is assessed at baseline, at the beginning of courses 1 and 3 (high-dose
chemotherapy) or courses 3 and 5 (standard chemotherapy), and then at 7, 12, and 18 months.

Patients are followed monthly.

PROJECTED ACCRUAL: A total of 430 patients (215 per treatment arm) will be accrued for this
study within 3 years.