Progress and obstacles in chemotherapy and combined modality treatment of small cell lung cancer

In order to assess the development of treatment of small cell lung cancer (SCLC), we analyzed a total of 183 patients who had been entered into our protocol studies since 1976. Between 1976 and 1981, 39 patients (20 LD and 19 ED) received COMP a 4-drug combination of cyclophoshpmide (CTX), vincristine (VCR), methotrexate and procarbazine. During the period, chest irradiation (RT) was optional for those with LD. Between 1981 and 1986, 112 patients (56 each of LD and ED) were treated with a cyclic alternating chemotherapy (CT) of COMP and VAN, a 3-drug combination of etoposide (VP-16), adriamycin (ADM) and nimustine. In this study, we randomized patients with LD either to receive CT alone or CT plus RT of 40 Gy to assess the role of RT in the treatment of LD. Thereafter, a pilot study of CAV-PVP hybrid CT has been conducted in 32 patients (16 each of LD and ED), in which CTX, ADM and VCR were given on day 1 (CAV), and cisplatin on day 8 and VP-16 on days 8 and 9 (PVP). RT was administered mandatory to LD in this study. the median survival time (MST) has been prolonged with an improvement of response rate in both LD and ED: the MST of LD was 11.1 months for COMP, 14.5 months for COMP-VAN, and 25.8 months for CAV-PVP (COMPVS COMP-VAN, p < 0.05; COMP-VAN vs CAV-PVP, p < 0.05), while that of ED was 7.8 months for COMP, 11.3 months for COMP-VAN, and 12.8 months for CAV-PVP (COMP vs CAV-PVP, p<0.05; otherwise, not significant). The randomized study comparing CT alone and CT plus RT revealed that RT played a substantail, but not significant, role for long-term survival in LD. Finally, 13 of 151 patients treated between 1976 and 1981 survived disease-free beyond 2 years. Of the long-term responders, 2 patients who had not received prophylactic cranial irradiation had the initial relapse in the brain and died of the disease at 50 and 51 months, respectively. These results imply that SCLC is potentially curable, but there are still many obstacles to achieve a cure in a substantial proportion of patients.