Limited-stage small cell lung cancer: current chemoradiotherapy treatment paradigms

Abstract

In the U.S., the prevalence of small cell lung cancer (SCLC) is declining, probably reflecting the decreasing prevalence of tobacco use. However, a significant number of patients will receive a diagnosis of SCLC, and approximately 40% of patients with SCLC will have limited-stage (LS) disease, which is potentially curable with the combination of chemotherapy and radiation therapy. The standard therapy for LS-SCLC is concurrent chemoradiotherapy, and the 5-year survival rate observed in clinical trials is approximately 25%. The standard chemotherapy remains cisplatin and etoposide, but carboplatin is frequently used in patients who cannot tolerate or have a contraindication to cisplatin. Substantial improvements in survival have been made through improvements in radiation therapy. Concurrent chemoradiotherapy is the preferred therapy for patients who are appropriate candidates. The optimal timing of concurrent chemoradiotherapy is during the first or second cycle, based on data from meta-analyses. The optimal radiation schedule and dose remain topics of debate, but 1.5 Gy twice daily to a total of 45 Gy and 1.8-2.0 Gy daily to a total dose of 60-70 Gy are commonly used treatments. For patients who obtain a near complete or complete response, prophylactic cranial radiation reduces the incidence of brain metastases and improves overall survival. The ongoing Radiation Therapy Oncology Group and Cancer and Leukemia Group B and the European and Canadian phase III trials will investigate different radiation treatment paradigms for patients with LS-SCLC, and completion of these trials is critical.

Figure 1.

CALGB 30610/RTOG 0538: Phase III trial of TRT regimens in patients with limited-stage small cell lung cancer receiving cisplatin and etoposide. *All patients will receive cisplatin, 80 mg/m² on day 1 and etoposide, 100 mg/m² on days 1, 2, and 3, every 21 days for four cycles. Prophylactic cranial radiation should be offered to all patients with a complete response or near complete response. Abbreviations: BID, twice daily; CALGB, Cancer and Leukemia Group B; fx, fraction; QD, daily; RTOG, Radiation Therapy Oncology Group; TRT, thoracic radiation therapy.

Figure 2.

CONVERT: Phase III trial of TRT in patients with limited-stage small cell lung cancer receiving cisplatin and etoposide. *All patients receive cisplatin, 25 mg/m² on days 1–3 or 75 mg/m² on day 1, and etoposide, 100 mg/m² on days 1–3 for four to six cycles. Abbreviations: BID, twice daily; CONVERT, Concurrent Once-daily Versus twice daily RadioTherapy; fx, fraction; TRT, thoracic radiation therapy.