Cisplatin for small-cell lung cancer

Small-cell lung cancer (SCLC) is a tumor highly sensitive to chemotherapy for which combination chemotherapy is the cornerstone of treatment. Antineoplastic activity has been shown for several agents, usually in the setting of minimal prior therapy. Active agents have minimal activity when used after previous chemotherapies. Cisplatin, which has only modest activity for SCLC, has not been adequately tested in the setting of minimal prior therapy, but is probably very active. Furthermore, response to cisplatin is probably dose-dependent. Synergy between agents is very important in treatment strategies, and cisplatin is synergistic with multiple agents. The EP combination (cisplatin, etoposide) is particularly synergistic for SCLC. Unlike most other combinations, EP produces consistent responses as a salvage regimen. When used as an initial treatment regimen or to alternate with other combinations, EP approximately produces the "state-of-the-art" anticipated results. When EP is administered with concurrent chest irradiation in limited disease, it produces response and survival results similar to more aggressive regimens. Thus, EP plus chest irradiation is a reasonable combination for patients not entering investigational studies, and EP may be the foundation for more aggressive combinations. CEP (high-dose EP, cyclophosphamide) caused an increase in response frequency in extensive disease. We added cisplatin to the combination of cyclophosphamide, doxorubicin, and etoposide (PACE). This four-drug combination pilot study was stopped early because of toxicities, and follow-up now suggests that survival may be prolonged. Further study of this and similar aggressive combinations appears warranted, and the use of colony-stimulating factors may allow for acceptable toxicity and further dose escalation.