ABSTRACT
AIM: This phase II study was conducted to evaluate the efficacy and safety of docetaxel and bevacizumab combination therapy in patients with previously-treated non-squamous non-small cell lung cancer (Nsq NSCLC). PATIENTS AND METHODS: Patients with histologically- or cytologically-confirmed Nsq NSCLC, 20-74 years of age, who had performance status 0-2, and had undergone at least one prior chemotherapy course were eligible for the study. Patients were treated with docetaxel (60 mg/m(2)) and bevacizumab (15 mg/kg) on day 1, which was repeated every three weeks until progressive disease or unacceptable toxicity occurred. The primary end-point was the response rate (RR) and the planned sample size was 28 patients. RESULTS: Between May 2010 and July 2011, 28 patients were enrolled (16 males, 12 females; median age=65 years; performance status 0/1: 19/9; adenocarcinoma/other: 22/6; number of prior chemotherapy courses 1/2/3 or more: 16/5/7). Twenty-eight patients were included in the toxicity analysis, out of whom 27 were evaluable for response. Objective response was observed in 18 patients (partial response in 18, stable disease in 8, progressive disease in 1); the RR and disease control rates were 66.7% and 96.0%, respectively. The median follow-up was 23.9 months, median progression-free survival was 7.2 months, and median overall survival was 21.6 months. The main toxicity associated with this regimen was myelosuppression (grade 3/4 neutropenia: 82.1%; febrile neutropenia: 21%). Mild non-hematological toxicity was observed but there was no severe bleeding. CONCLUSION: The combination regimen of docetaxel-plus-bevacizumab is very active in patients with previously-treated Nsq NSCLC and warrants further research.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab , Carcinoma, Non-Small-Cell Lung/mortality , Chemotherapy, Adjuvant , Docetaxel , Female , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Neoplasm Staging , Taxoids/administration & dosage , Treatment OutcomeABSTRACT
BACKGROUND: Although pemetrexed/cisplatin (P-C) is a standard treatment for advanced non-squamous non-small cell lung cancer (Nsq-NSCLC), neither its efficacy nor the effects of potential differences between driver mutations, such as the anaplastic lymphoma kinase (ALK) translocation and epidermal growth factor receptor (EGFR) mutations, have been thoroughly examined. PATIENTS AND METHODS: A single-arm phase II study of P-C was conducted in Japanese patients with chemo-naïve advanced Nsq-NSCLC. Patients received four cycles of pemetrexed (500 mg/m(2)) combined with cisplatin (75 mg/m(2)) on day 1 every three weeks. The primary end-point was the response rate (RR) and the secondary end-points were toxicity, progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 50 patients were analyzed (males, 68%; adenocarcinoma, 80%). The RR was 44.0%. The median PFS and OS were 4.3 months and 22.2 months, respectively. Toxicities were mild, and no new toxicity profiles were identified. Among the 39 out of 50 samples, six (15.4%) presented ALK translocation and nine (23.1%) presented EGFR mutations; of the remaining patients, 24 (61.5%) were wild-type for both ALK and EGFR. Objective response was observed in two out of six patients with ALK translocations, six out of nine with EGFR mutations, and in 11 (45.8%) wild-type patients. CONCLUSION: The combination of pemetrexed and cisplatin was effective and safe in Japanese patients with Nsq-NSCLC. We did not observe obvious differences in the efficacy of P-C between patients with ALK translocation or EGFR mutation and those with wild-type genotype.