Systemic treatment of small cell lung cancer

Small cell lung cancer (SCLC) accounts for 20-25% of all lung cancer and is characterized by an aggressive clinical course with early dissemination and extremely high risk of recurrence. Chemotherapy has been the cornerstone of treatment, with high response rates including complete responses. Despite the sensitivity of this disease to cytotoxic drugs, the majority of patients will face recurrence and die of the disease within two years. For more than thirty years, investigators have conducted numerous trials using different drug regimens and schedules, as well as different therapeutic modalities. The combination of cyclophosphamide, doxorubicin (adriamycin) and vincristine (CAV) was one of the first widely accepted regimens for the treatment of SCLC. Later, CAV and its hybrids were replaced by the similarly effective but less toxic regimen of cisplatin and etoposide (PE). Clinical investigators have tried different approaches to improve the efficacy of these regimens, such as alternating CAV/PE; consolidation and maintenance therapy; intensive treatment with high-dose chemotherapy; increased frequency of drug administration; or high dose therapy with stem cell support - all with no definitive successes, leaving PE as the standard treatment for patients with SCLC. The recent arrival of new chemotherapy agents such as topotecan, irinotecan, and taxanes may represent a step forward in the treatment of this disease. The most promising regimen is the combination of irinotecan and cisplatin which, according to Japanese investigators, achieves a significantly better survival than standard PE. If validated by confirmatory trials, this combination could well become the new standard treatment for extensive chemotherapy-naïve SCLC. Biological agents are also being widely investigated, including vaccines, matrix metalloproteinase inhibitors, anti-sense therapy, and monoclonal antibodies. Advances in molecular biology will hopefully contribute to progress in the treatment of this lethal disease.