Small-Cell Lung Cancer: Is There a Standard Therapy?

ABSTRACT: For more than 25 years, chemotherapy has been the cornerstone of treatment for small-cell lung cancer. Many studies have tested a wide variety of drugs in different combinations, resulting in a number of standard combination chemotherapy options. Radiotherapy to the primary tumor, after having been out of favor for a time, is now considered an element of standard therapy for patients with limited disease, although a number of questions remain concerning its optimal use. Because the overall outcome of therapy for small-cell lung cancer is not at all satisfying, further research is needed to find a better use of old and new drugs. This article provides a historic overview of therapy for small-cell lung cancer, followed by examples of emerging concepts and current research in such areas as dose escalation, second-line therapy, and new drugs. Selection of optimal first-line therapy for the individual patient is also discussed, based on disease stage, performance status, and other considerations. [ONCOLOGY 12(Suppl 2):25-30, 1998]

In the late 1960s, it became clear that small-cell lung cancer (SCLC) is distinct from other histologic types of lung cancer and could be differentiated in a number of ways. At the time of diagnosis, for example, small-cell lung cancer usually manifests as a central tumor, with dissemination to the locoregional lymph nodes and signs of dissemination to distant sites in the vast majority of patients. Further, it is often associated with paraneoplastic signs like inappropriate antidiuretic hormone production, Cushing’s syndrome, and Eaton-Lambert syndrome.

The general consensus about the approach to treating this tumor changed considerably after it became clear that despite any apparent success of local treatment, ie, radiotherapy or surgery in selected patients, the short- and long-term prognosis for patients with small-cell lung cancer was very poor. In fact it was questionable whether therapy offered any benefit over no treatment, which resulted in a median survival of 6 weeks for patients with extensive disease and 3 months for those with limited disease. Despite the questionable success of radiotherapy as a single-treatment modality for limited-disease patients, the staging system for this tumor is still based on the potential to create a radiotherapy field that will encompass all known tumor sites.

The first small step forward in the treatment of small-cell lung cancer came after some effect was seen with the alkylating agent cyclophosphamide (Cytoxan, Neosar), one of the cytotoxic drugs available at that time.[1] Since then, small-cell lung cancer has been considered to be a systemic disease that requires systemic therapy.

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