Cooperative Group Research Endeavors in Small-cell Lung Cancer: Current and Future Directions

Current and Future Directions

Randeep Sangha; Primo N. Lara, Jr.; Alex A. Adjei; Paul Baas; Hak Choy; Laurie E. Gaspar; Glenwood Goss; Nagahiro Saijo; Joan H. Schiller; Everett E. Vokes; David R. Gandara

Disclosures

Clin Lung Cancer. 2009;10(5) 

In This Article

Radiation Therapy Oncology Group

In lung cancer, RTOG research endeavors are intended to decipher the optimal methods of using radiation therapy in a consistently effective and safe manner. Besides being a key collaborator in the CALGB 30610 trial, designated as RTOG 0538 within the group, RTOG has been instrumental in discerning the best method of delivering PCI in LS-SCLC. RTOG 0212, closed to accrual in February 2008, was designed to determine the optimal dose of PCI after a meta-analysis suggested a reduced incidence of brain metastases with higher PCI doses. Patients with LS-SCLC who were complete responders to primary treatment were randomized to receive standard (25-Gy/10-fraction/12 days) or higher PCI doses (36-Gy) administered using either conventional (18 fractions/24 days) or accelerated hyperfractionated radiation therapy (24 twicedaily fractions/16 days). This phase II/III trial had significant contributions from CALBG, ECOG, EORTC, and SWOG, with results presented at the 2008 American Society of Clinical Oncology meeting. A total of 720 patients were enrolled, and although there was a nonsignificant trend for reduced 2-year brain metastases incidence with high-dose PCI compared with standard-dose PCI (24% vs. 30%; P = .13), there was a significantly marked increase in chest relapse (48% vs. 40%; P = .02) and mortality (2-year OS 37% with high-dose PCI vs. 42% with standard-dose PCI; P = .03).[36] Thus, the prevailing PCI dose of 25 Gy remains the standard of care for LS-SCLC.

Intergroup 0096 showed a survival benefit using an accelerated fractionation schedule compared with daily radiation therapy. RTOG 0239, a phase II trial, evaluated an innovative radiation therapy design where once-daily radiation therapy along with concurrent chemotherapy was given followed by a hyperfractionated schedule, a concomitant boost, in LS-SCLC (61.2 Gy/34 fractions). This schedule was found to be tolerable but was associated with a high incidence of myelosuppression.[37] RTOG 0623 is a phase II trial designed to overcome this adverse event by incorporating filgrastim with concurrent chemoradiation therapy and pegfilgrastim, with adjuvant cisplatin/etoposide chemotherapy in patients with LS-SCLC. Historically, hematopoietic growth factors have not been recommended during combined modality chemoradiation therapy based on early theoretical concerns that growth factors might release progenitor cells and expose them to the damaging effects of radiation therapy, but significant improvements in supportive care and delivery of radiation therapy could make these concerns less applicable. The primary endpoint of RTOG 0623 is to evaluate the safety and efficacy of filgrastim in reducing grade ≥ 3 neutropenia when given with concurrent chemoradiation. Unfortunately, this trial is accruing poorly and is expected to close soon.

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