Pilot study of accelerated radiotherapy with concurrent chemotherapy for stage III non-small cell lung cancer

The purpose of this pilot study was to determine the safety and feasibility of accelerated fractionation (via concomitant boost) radiotherapy (XRT) with concurrent carboplatin/paclitaxel chemotherapy for locally advanced stage III non-small cell lung carcinoma. Radiotherapy consisted of 3-dimensional conformal techniques to 60 Gy continuous course, over 4 weeks, via 3-dimensional conformal techniques. Once-daily treatments were used; the large field (including gross tumor and selected regional nodes) was given a daily dose of 2.2 Gy (to 44 Gy), with a 0.8 Gy concomitant boost (field within a field) for an additional 16 Gy to the gross tumor volume. Weekly carboplatin at an area under the curve (AUC) of 2 plus paclitaxel 50 mg/m2 were given during XRT, followed by two cycles of systemic-dose carboplatin AUC 6, every 4 weeks plus paclitaxel 100 mg/m2 , 3 weeks out of 4, were planned. The nutritional supplement glutamine 10 mg 3 times per day was prescribed in an effort to decrease esophagitis. Before the early closure of this study, five patients were enrolled, of whom four were evaluable for toxicity/feasibility. No patient experienced grade 3+ acute nonhematologic toxicity during concurrent chemoradiotherapy. Hematologic toxicity was significant in the post-XRT consolidation phase, resulting in dose reduction and/or discontinuation in three of four patients. More notably, two patients experienced serious nonhematologic late toxicity. One patient developed a grade 4 tracheoesophageal fistula that probably contributed to her death 6 months after treatment, and one patient developed grade 3 pulmonary complications including severe oxygen-dependent radiation pneumonopathy. Three patients are alive without disease progression at 14, 20, and 21 months follow-up. Despite the use of 3-dimensional conformal technology, this regimen of concomitant boost accelerated hypofractionated XRT with concurrent and systemic chemotherapy was excessively toxic and not feasible. Extreme caution must be exercised in designing studies of XRT dose intensification with concurrent chemotherapy.