Treatment of Small Cell Lung Cancer: Two-drug versus four-drug chemotherapy and loco-regional irradiation with or without prophylactic cranial irradiation

Fifty-five patients with untreated small cell lung cancer were allocated randomly to receive either a standard 2-drug or a 4-drug chemotherapy regimen. The patients were further randomized to receive or not to receive prophylactic cranial irradiation (PCI) 40 Gy/20 fractions/4 weeks. Each patient also received split-course irradiation against the primary tumour (55 Gy/25 fractions/8 weeks), the mediastinum, and the supraclavicular areas. The standard 2-drug regimen consisted of cyclophosphamide 10 mg/kg i.v. days 1-4 and vincristine 1 mg i.v. days 1 + 4; every 4 weeks. The 4-drug regimen comprised cyclophosphamide 10 mg/kg i.v. days 1-3, vincristine 2 mg i.v. day 1 and 1 mg i.v. day 5, methotrexate 30 mg i.v. days 3 and 5, CCNU 80 mg/m2 i.v. day 2; every 7 weeks. The total treatment time for both protocols was 9 to 12 months. Objective response after 2 cycles of chemotherapy was seen in 46% of patients with the 2-drug regimen and in 56% with the 4-drug regimen. Local radiotherapy increased the response rates to 58% and 90% respectively. The median survival time was 12 months with the 2-drug regimen and 14 months with the 4-drug regimen. The 2-year and 3-year survival rates were 11% and 0% in the 2-drug group and 19% and 15% in the 4-drug group respectively. Toxicity was more severe in the 4-drug group with 4 deaths due to myelosuppression. Altogether, 25 patients received PCI. This did not in any subgroup increase median survival significantly but a reduction of relapses in the central nervous system was seen. Median survival was 13 months with versus 10 months without PCI; 2-year survival rates were 15% and 6% respectively. Morbidity due to PCI did not occur. Although no statistically significant survival advantage could be documented, there was obviously a higher rate of complete responses with multidrug therapy, and longer median duration of remission, median survival and maximal survival.