A phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small-cell lung cancer (A Vanderbilt cancer center affiliate network study)

Purpose: We conducted a prospective phase II study to determine the respons e rate, toxicity, and survival rate of concurrent weekly paclitaxel, carbop latin, and hyperfractionated radiation therapy (paclitaxel/carboplatin/HFX RT) followed by 2 cycles of paclitaxel and carboplatin for locally advanced unresectable non-small cell lung cancer (NSCLC), The weekly paclitaxel and carboplatin regimen was designed to optimize the radiosensitizing properti es of paclitaxel during the concurrent phase of treatment. Methods and Materials: Forty-three patients with unresectable stage IIIA an d IIIB NSCLC from the Vanderbilt Cancer Center and-Affiliate Network (VCCAN ) institutions were entered onto the study from June 1996 until May 1997, W eekly intravenous (IV) paclitaxel (50 mg/m(2)/l-hour) and weekly carboplati n (AUC 2) plus concurrent hyperfractionated chest RT (1.2 Gy/BID/69.6 Gy) w ere delivered for 6 weeks followed by 2 cycles of paclitaxel (200 mg/m(2)) and carboplatin (AUC 6). Results: Forty-two patients were evaluable for response and toxicities, Thr ee patients achieved a complete response (7.2%) and 30 patients achieved a partial response (71.4%), for an overall response rate of 78.6% [95% C.I. ( 66.2%-91.0%)]. The 1- and 2-year overall and progression-free survival rate s of all 43 patients were 61.6% and 35% respectively, with a median surviva l time of 14.3 months. The median follow-up time was 14 months. Esophagitis was the principal toxicity. Grade 3 or 4 esophagitis occurred in 11 patien ts (26%), There was an incidence of 7% grade 3 and 9.5% grade 4 pulmonary t oxicities. Conclusions: Weekly paclitaxel, carboplatin, plus concurrent hyperfractiona ted RT is a well-tolerated outpatient regimen. The response rate from this regimen is encouraging and appears to be at least equivalent to the more to xic chemoradiation trials. These findings warrant further clinical evaluati on of weekly paclitaxel/carboplatin/HFX RT in a phase III study. (C) 2000 E lsevier Science Inc.