PURPOSE: Randomized clinical trials failed to show a survival benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus concurrent chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC), with preclinical data suggesting potential negative interactions. In contrast, pilot trials of the EGFR-targeted antibody, cetuximab, plus chemotherapy suggested enhanced antitumor activity. This randomized phase II trial was designed to select a cetuximab plus chemotherapy regimen for phase III evaluation. PATIENTS AND METHODS: Treatment-naive patients with advanced-stage NSCLC were randomly assigned to receive paclitaxel (225 mg/m(2)) and carboplatin (area under the curve, 6) every 3 weeks plus concurrent cetuximab (400 mg/m(2) loading dose followed by 250 mg/m(2) weekly) for four cycles followed by maintenance cetuximab or sequential paclitaxel-carboplatin for four cycles followed by cetuximab. RESULTS: Of 242 patients enrolled, 224 were eligible and assessable for response (106 and 118 patients in the concurrent and sequential arms, respectively). With a median follow-up time of 32 months, the median overall survival was 10.9 months (95% CI, 9.2 to 13.0 months) for patients receiving concurrent therapy and 10.7 months (95% CI, 8.5 to 12.8 months) for patients receiving sequential therapy (P = .57); 1-year survival rates were 45% (95% CI, 36% to 54%) and 44% (95% CI, 35% to 53%), respectively. Response rates and progression-free survival times were similar in both arms, as was grade 3 rash, whereas sensory neuropathy was higher in the concurrent arm (15% v 5% in the sequential arm; P = .036). CONCLUSION: Although both regimens met the efficacy criterion for continued evaluation, the concurrent regimen of paclitaxel/carboplatin plus cetuximab was chosen.
RCT Entities:
PURPOSE: Randomized clinical trials failed to show a survival benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus concurrent chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC), with preclinical data suggesting potential negative interactions. In contrast, pilot trials of the EGFR-targeted antibody, cetuximab, plus chemotherapy suggested enhanced antitumor activity. This randomized phase II trial was designed to select a cetuximab plus chemotherapy regimen for phase III evaluation. PATIENTS AND METHODS: Treatment-naive patients with advanced-stage NSCLC were randomly assigned to receive paclitaxel (225 mg/m(2)) and carboplatin (area under the curve, 6) every 3 weeks plus concurrent cetuximab (400 mg/m(2) loading dose followed by 250 mg/m(2) weekly) for four cycles followed by maintenance cetuximab or sequential paclitaxel-carboplatin for four cycles followed by cetuximab. RESULTS: Of 242 patients enrolled, 224 were eligible and assessable for response (106 and 118 patients in the concurrent and sequential arms, respectively). With a median follow-up time of 32 months, the median overall survival was 10.9 months (95% CI, 9.2 to 13.0 months) for patients receiving concurrent therapy and 10.7 months (95% CI, 8.5 to 12.8 months) for patients receiving sequential therapy (P = .57); 1-year survival rates were 45% (95% CI, 36% to 54%) and 44% (95% CI, 35% to 53%), respectively. Response rates and progression-free survival times were similar in both arms, as was grade 3 rash, whereas sensory neuropathy was higher in the concurrent arm (15% v 5% in the sequential arm; P = .036). CONCLUSION: Although both regimens met the efficacy criterion for continued evaluation, the concurrent regimen of paclitaxel/carboplatin plus cetuximab was chosen.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: Joan H Schiller; David Harrington; Chandra P Belani; Corey Langer; Alan Sandler; James Krook; Junming Zhu; David H Johnson Journal: N Engl J Med Date: 2002-01-10 Impact factor: 91.245
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Authors: Giuseppe Giaccone; Roy S Herbst; Christian Manegold; Giorgio Scagliotti; Rafael Rosell; Vincent Miller; Ronald B Natale; Joan H Schiller; Joachim Von Pawel; Anna Pluzanska; Ulrich Gatzemeier; John Grous; Judith S Ochs; Steven D Averbuch; Michael K Wolf; Pamela Rennie; Abderrahim Fandi; David H Johnson Journal: J Clin Oncol Date: 2004-03-01 Impact factor: 44.544
Authors: Shirin Khambata-Ford; Christopher T Harbison; Lowell L Hart; Melissa Awad; Li-An Xu; Christine E Horak; Shaker Dakhil; Robert C Hermann; Thomas J Lynch; Martin R Weber Journal: J Clin Oncol Date: 2010-01-25 Impact factor: 44.544
Authors: Ezzeldin M Ibrahim; Khaled M Abouelkhair; Osama A Al-Masri; Najeeb C Chaudry; Ghieth A Kazkaz Journal: Lung Date: 2011-03-20 Impact factor: 2.584
Authors: Roy S Herbst; Mary W Redman; Edward S Kim; Thomas J Semrad; Lyudmila Bazhenova; Gregory Masters; Kurt Oettel; Perry Guaglianone; Christopher Reynolds; Anand Karnad; Susanne M Arnold; Marileila Varella-Garcia; James Moon; Philip C Mack; Charles D Blanke; Fred R Hirsch; Karen Kelly; David R Gandara Journal: Lancet Oncol Date: 2017-11-20 Impact factor: 41.316