A multicenter phase II study of docetaxel, oxaliplatin, and bevacizumab in first-line therapy for unresectable locally advanced or metastatic non-squamous cell histology non-small-cell lung cancer (NSCLC)
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Platinum-based doublets are standard of care for advanced non-small-cell lung cancer (NSCLC). The combination of docetaxel and oxaliplatin has shown acceptable toxicity and encouraging activity. This phase II study aimed to determine the safety and efficacy of this doublet with bevacizumab as first-line treatment for stage IIIB/IV NSCLC.
Newly diagnosed patients ≥18 years with histologically proven non-squamous NSCLC and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2 received six 21-day cycles of docetaxel, oxaliplatin, and bevacizumab followed by single-agent bevacizumab for a total of 1 year. Primary efficacy end point was radiographically documented progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), time to treatment failure, and safety.
Fifty-three patients were enrolled. Median age was 62.0 years, 71.7 % male, 79.2 % Caucasian. A total of 88.7 % had stage IV or recurrent disease; 94.3 % adenocarcinoma; and 94.3 % ECOG PS 0 or 1. Efficacy results are as follows: median PFS 5.6 months, ORR 30.2 % (complete response 1.9 %, partial response 28.3 %); 37.7 % stable disease; and OS 14.0 months. At least one adverse event (AE) was reported in all patients (n = 52); 98.1 % of AEs were treatment related. The most common treatment-emergent grade ≥3 AEs were neutropenia (15.4 %), diarrhea (13.5 %), and fatigue (11.5 %). A serious AE was present in 32.7 %; the most common were pneumonia (7.7 %) and abdominal pain (5.8 %). Dehydration, diarrhea, febrile neutropenia, sepsis, and supraventricular tachycardia each occurred in 3.8 %.
The addition of bevacizumab to docetaxel/oxaliplatin is effective with an acceptable safety profile in patients with chemotherapy-naïve advanced NSCLC.
KeywordsOxaliplatin Docetaxel Bevacizumab Non-small-cell lung cancer Metastatic disease
Dr. Luis E. Raez was a member of the Speakers’ Bureau of Genentech, sanofi-aventis, and Eli Lilly US Oncology. Dr. Raez receives research support from Genentech and Eli Lilly Oncology. Dr. Edgardo S. Santos is a member of the Speakers’ Bureau of Genentech, sanofi-aventis, and Eli Lilly US Oncology. This study was sponsored by Sanofi US. All summaries and statistical analyses were performed by United BioSource Corporation.
- 4.Dancey J, Shepherd FA, Gralla RJ et al (2004) Quality of life assessment of second-line docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy: results of a prospective, randomized phase III trial. Lung Cancer 43:183–194PubMedCrossRefGoogle Scholar
- 8.Manegold C, von Pawel J, Zatloukal P (2007) Randomised, double-blind multicentre phase III study of bevacizumab in combination with cisplatin and gemcitabine in chemotherapy-naïve patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC): BO17704. J Clin Oncol 25((18 suppl)):LBA7514Google Scholar
- 10.Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216PubMedCrossRefGoogle Scholar
- 12.Chow SC, Shao J, Wang H (eds) (2003) Sample size calculations in clinical research. CRC Press, New York, NYGoogle Scholar
- 17.Reck M, von Pawel J, Zatloukal P et al (2010) for the BO17704 Study Group. Overall survival with cisplatin–gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomized phase III trial (AVAiL). Ann Oncol 21:1804–1809PubMedCrossRefGoogle Scholar
- 18.Kubota K, Kawahara M, Ogawara M et al (2008) for the Japan Multi-National Trial Organisation. Vinorelbine plus gemcitabine followed by docetaxel versus carboplatin plus paclitaxel in patients with advanced non-small-cell lung cancer: a randomised, open-label, phase III study. Lancet Oncol 9:1135–1142PubMedCrossRefGoogle Scholar
- 20.Laack E, Dickgreber N, Müller T et al (2004) Randomized phase III study of gemcitabine and vinorelbine versus gemcitabine, vinorelbine, and cisplatin in the treatment of advanced non-small-cell lung cancer: from the German and Swiss Lung Cancer Study Group. J Clin Oncol 22:2348–2356PubMedCrossRefGoogle Scholar
- 26.Radhakrishnann A, Bitran JD, Milton DT et al (2009) Docetaxel and oxaliplatin as first-line therapy for advanced non-small cell lung cancer: a phase II trial. J Chemother 21:439–444Google Scholar