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Zhu, Andrew X, Dr; Meyerhardt, Jeffrey A, MD; Blaszkowsky, Lawrence S, MD; Kambadakone, Avinash R, MD; Muzikansky, Alona, MS; Zheng, Hui, PhD; Clark, Jeffrey W, MD; Abrams, Thomas A, MD; Chan, Jennifer A, MD; Enzinger, Peter C, MD; Bhargava, Pankaj, MD; Kwak, Eunice L, MD; Allen, Jill N, MD; Jain, Sanjay R, MD; Stuart, Keith, MD; Horgan, Kerry, BA; Sheehan, Susan, RN; Fuchs, Charles S, MD; Ryan, David P, MD; Sahani, Dushyant V, MD
The lancet oncology, 2010, 2010-Jan, 2010-01-00, 20100101, Letnik: 11, Številka: 1Journal Article
Summary Background Previous phase 2 studies have shown antitumour activity with gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary-tract cancers (BTCs). In this phase 2 study, we assessed the efficacy and safety of combined bevacizumab with GEMOX (GEMOX-B) in patients with advanced BTCs, and investigated how changes in 18-fluorodeoxyglucose (18 FFDG)-PET correlate with clinical outcome. Methods Patients with advanced measurable BTCs were given the following treatment on days 1 and 15 of a 28-day cycle: bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m2 (10 mg/m2 per min) and oxaliplatin 85 mg/m2 (2-h infusion). 18 FFDG-PET scans were obtained at baseline and after completion of the second cycle. The primary endpoint was progression-free survival (PFS). Efficacy and safety analyses were by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00361231. Findings 35 patients were enrolled and evaluable for efficacy and toxicity. Median PFS was 7·0 months (95% CI 5·3–10·3), and PFS at 6 months was 63% (47–79), which was below the targeted rate of 70%. Grade 3–4 toxic effects included neutropenia (n=7), raised alanine aminotransferase concentrations (n=5), peripheral neuropathy (n=5), and hypertension (n=5). 18 FFDG-PET scans showed a significant decrease in maximum standardised uptake value (SUVmax ) after two cycles of treatment (5·72 SD 2·01 at baseline; 3·73 SD 1·88 after two cycles; p<0·0001). These changes were more pronounced in patients with partial response or stable disease than those with progressive disease (24 patients, −2·80 SD 1·95 vs five patients, 1·41 SD 3·13; p=0·009). Change in SUVmax was a significant predictor of PFS (HR 1·35, 1·14–1·60, p=0·0006) and overall survival (1·25, 1·05–1·50, p=0·01). Interpretation GEMOX-B showed antitumour activity with tolerable safety in patients with advanced BTCs. Decreases in SUVmax on 18 FFDG-PET scans after treatment were associated with disease control and increases in PFS and overall survival. Funding Genentech Oncology and Sanofi-Aventis.
