Systemic therapy for limited stage small cell lung carcinoma

Systemic treatment in small cell lung carcinoma has been a challenge for oncologists for decades. The high propensity for recurrence is usually due to distant metastasis, which makes systemic treatment an essential component of treatment in small cell lung carcinoma. The regimen of cisplatin and etoposide (established in the mid-1980's) concurrently with thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) remains the standard of care in limited stage disease. Despite numerous trials, this regimen has not been improved upon. The standard combination regimen of cisplatin and etoposide has been compared to alternative platinum-containing regimens with drugs like epirubicin, irinotecan, paclitaxel, topotecan, pemetrexed, amrubicin and belotecan. Non-platinum containing regimens like ifosfamide and etoposide have also been tested. Attempts to intensify therapy have included the addition of a third drug like paclitaxel, ifosfamide, tirapazamine, tamoxifen, and thalidomide. Maintenance therapy following induction with chemotherapy, vandetanib and interferon-alpha have also been attempted. Molecularly directed targeted therapies and immunotherapeutic agents are areas of active research. In this review, we discuss the various systemic therapy options in limited stage small cell lung carcinoma, from the historical regimens to the modernday therapy and promising areas of research. We also discuss the role of growth factors, the optimal number of chemotherapy cycles, the use of prognostic and predictive factors, the optimal timing of chemotherapy and the treatment of special populations of patients including older patients, and patients with comorbidities.