A phase II trial of concurrent chemotherapy with intravenous cisplatin and vinorelbine and radiotherapy followed by consolidation chemotherapy with oral vinorelbine in locally advanced non-small cell lung cancer (NSCLC): the CONCAVE study

Aim: Despite recent advances, outcomes for patients with stage III non–small cell lung cancer (NSCLC) with concurrent chemoradiotherapy (CRT) remain poor. We evaluated the combination of ciplatin/vinorelbine and concurrent thoracic radiotherapy followed by consolidation oral vinorelbine in this phase II study. Methods: Eligible patients with unresectable stage III NSCLC received cisplatin intravenous (IV) 40 mg/m and vinorelbine IV 20 mg/m on days 1, 8, 22 and 29 concurrent with thoracic radiotherapy of 60 Gy in 30 fractions. Four to eight weeks later, oral vinorelbine 60 mg/m day 1 and 8 every 3 weeks was given for 3 cycles. The primary end point was overall response rate (ORR). Secondary end points were safety, quality of life, progression-free survival (PFS) and overall survival (OS). Results: Twenty-seven eligible patients were enrolled from December 2007 to June 2010 before the trial was prematurely closed due to toxicity concerns. The median age was 63 years (range, 42–71), 56% were male, 52% ECOG 0 and 52% stage IIIa. The ORR was 81% (including 37% complete response rate) and disease control rate of 93%. The median PFS was 11 months and median OS was 26 months. Consolidation vinorelbine was associated with significant grade 3/4 toxicity (68%) including grade 3–5 febrile neutropenia (27%) and respiratory infections (36%) including two deaths in the consolidation phase (9%). Conclusions: Consolidation oral vinorelbine after CRT was associated with significant toxicity. Overall, this regimen achieved a high ORR and survival results comparable to other CRT protocols but the significant toxicity precludes further evaluation of this approach.