Concurrent chemoradiation with cisplatin and vinorelbine followed by consolidation with oral vinorelbine in locally advanced non-small cell lung cancer (NSCLC): the phase II CONCAVE study.
OBJECTIVE
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/m2and vinorelbine IV 20 mg/m2on 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/m2day 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.
Cancer Care Services, The Royal Brisbane and Women's Hospital, Queensland, Australia.|School of Medicine, University of Queensland, Queensland, Australia.
Brett Gm
BG
Hughes
Cancer Care Services, The Royal Brisbane and Women's Hospital, Queensland, Australia.|School of Medicine, University of Queensland, Queensland, Australia.|Queensland Institute of Medical Research, Queensland, Australia.
Elizabeth
E
Ahern
School of Medicine, University of Queensland, Queensland, Australia.|Cancer Care Services, The Princess Alexandra Hospital, Queensland, Australia.
Margot
M
Lehman
Cancer Care Services, The Royal Brisbane and Women's Hospital, Queensland, Australia.
Gary
G
Pratt
Respiratory Medicine, The Princess Alexandra Hospital, Queensland, Australia.
Margaret
M
Dauth
Cancer Care Services, The Royal Brisbane and Women's Hospital, Queensland, Australia.
Wendy
W
Pritchard
Queensland Institute of Medical Research, Queensland, Australia.
Leesa
L
Wockner
Greenslopes Private Hospital, Queensland, Australia.
Keith
K
Horwood
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000077235:Vinorelbine
D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine
chemoradiotherapy; consolidation; locally advanced; lung cancer; non-small cell; vinorelbine