Chemotherapy of small-cell carcinoma of lung: A randomized comparison of alternating and sequential combination chemotherapy programs

One hundred forty-seven eligible patients with small-cell carcinoma of the lung (SCCL) have been randomized to receive alternating (A) or sequential (S) combination chemotherapy. Initial treatment was with three cycles of VAM (A) or two cycles of POCC (S). VAM consists of VP16-213 200 mg/m² intravenously (IV) day 1, Adriamycin (Adria Laboratories, Columbus, Ohio) 50 mg/m² IV day 1, and methotrexate 30 mg/m² IV day 1 repeated at 21-day intervals. POCC consists of cyclophosphamide 600 mg/m² IV days 1 and 8, vincristine 1.6 mg/m² (maximum, 2 mg) IV days 1 and 8, CCNU 60 mg/m² po day 1, and procarbazine 100 mg/m² po days 2 through 15. After initial treatment, all patients received whole brain radiation therapy (3,000 rad/10 fraction/2 wk). Patients with limited disease in addition received irradiation encompassing the tumor, hilar, mediastinal, and supraclavicular regions (5,000 rad/25 fractions/5 wk). After radiation, patients on arm A received POCC alternating with VAM; patients on arm 5 received POCC until progression when they were to be treated with VAM. The alternating arm was superior with respect to rate of complete remission (CR), median disease-free survival (MDFS), and median survival (MS). The advantage of alternating therapy was not as clearly demonstrated in the limited disease groups when interposition of involved field radiation delayed the initiation of the alternating schedule. In limited disease alone, comparing arm A with arm S, no statistically significant differences were noted. The GR rate was 42% v 54%, MDFS was 14 v 10 months, and MS was 16 v 10 months. In extensive disease, the CR rate was 44% v 20% (P=.03), MDFS was 6 v 4 months (P=.003), and MS was 10 v 7 months (P=.001). Improved treatment outcome in SCCL is achieved when combination chemotherapy regimens of similar effectiveness are administered in an alternating rather than sequential schedule.