Current perspectives in the treatment of small cell lung cancer

Abstract

Neither chemotherapy nor radiotherapy alone is adequate to treat both bulky local disease and the almost universal distant micrometastases of small cell lung cancer (SCLC). Despite improved overall and 2-year survival rates associated with combining the two treatment modalities, however, their potential for toxic interaction demands careful consideration. The specific toxicity profile of the chemotherapeutic agent used must be calculated and balanced with the radiotherapy dose, fractionation, volume, and timing with chemotherapy to give the patient the maximum benefit and the least amount of risk. Results of clinical trials indicate that fractionation of the radiation dose takes advantage of the fact that fractionation causes less damage to and allows for repair of normal tissue, whereas the tumor cells of SCLC are killed exponentially by even small radiation doses per fraction. Further evaluation of radiation volume is needed to answer questions on the risk-benefit ratio of normal lung exposure versus complete coverage of areas of potential metastasis, and to determine whether dose of volume is the more critical factor for lung toxicity. Finally, the timing of radiotherapy also must be studied further. Early radiotherapy offers the potential for killing small cells before they migrate, but attempts to compensate for such early exposure may lead to subtherapeutic doses of chemotherapy and, thus, to lower response rates.