Small cell lung cancer: defining a role for emerging platinum drugs

Small cell lung cancer (SCLC) is characterized by early dissemination and a rapid, aggressive clinical course. It has, however, marked susceptibility to both chemotherapy and radiotherapy, although treatment is complicated by the fact that SCLC tumors invariably develop resistance to multiple chemotherapeutic agents. Local therapy is rarely of benefit in SCLC because three-quarters of patients present with metastatic disease and many of the remaining patients are thought to have micrometastatic disease. Chemotherapy is, therefore, the cornerstone of treatment. Of the many combination regimens used, etoposide/cisplatin or etoposide/carboplatin have emerged as the regimens of choice because they offer a good therapeutic index and can be combined with radiotherapy. Response to second-line therapy remains consistently poor. As the prototype platinum compound, cisplatin has played a major role in the management of SCLC. Although its exact contribution to the treatment of SCLC has been difficult to ascertain, a recent meta-analysis reported a significant 1-year survival advantage of approximately 4% with cisplatin-containing regimens versus regimens without. However, cisplatin is characterized by several serious adverse events and, like other chemotherapeutic agents, is eventually rendered ineffective against SCLC because of acquired resistance. Several new platinum formulations or compounds are showing promising activity in SCLC. The impetus for their development has been to circumvent cisplatin resistance or to improve upon the toxicity profile of cisplatin. If the early promise shown by these compounds is confirmed in the clinic, they may offer a new approach to the treatment of SCLC, including recurrent disease for which limited treatment options are currently available.