Docetaxel, oxaliplatin, and capecitabine combination chemotherapy for metastatic gastric cancer

Gastric Cancer Docetaxel, oxaliplatin, and capecitabine combination chemotherapy for metastatic gastric cancer Luigi Di Lauro 0 1 2 3 4 5 6 Patrizia Vici 0 1 2 3 4 5 6 Franca Belli 0 1 2 3 4 5 6 Silverio Tomao 0 1 2 3 4 5 6 Silvia Ileana Fattoruso 0 1 2 3 4 5 6 Maria Grazia Arena 0 1 2 3 4 5 6 Laura Pizzuti 0 1 2 3 4 5 6 Diana Giannarelli 0 1 2 3 4 5 6 Giancarlo Paoletti 0 1 2 3 4 5 6 Maddalena Barba 0 1 2 3 4 5 6 Domenico Sergi 0 1 2 3 4 5 6 Marcello Maugeri-Sacca` 0 1 2 3 4 5 6 0 S. Tomao Oncology Unit, Department of Medical-Surgical Sciences and Biotechnologies, ''Sapienza'' University of Rome , Latina , Italy 1 F. Belli Division of Oncology, Spolverini Hospital , Ariccia , Italy 2 L. Di Lauro (&) P. Vici L. Pizzuti G. Paoletti M. Barba D. Sergi M. Maugeri-Sacca` (&) Division of Medical Oncology B, ''Regina Elena'' National Cancer Institute , Via Elio Chianesi 53, 00144 Rome , Italy 3 M. Maugeri-Sacca` Scientific Direction, ''Regina Elena'' National Cancer Institute , Rome , Italy 4 D. Giannarelli Division of Biostatistics, ''Regina Elena'' National Cancer Institute , Rome , Italy 5 M. G. Arena Division of Oncology, Toraldo Hospital , Tropea , Italy 6 S. I. Fattoruso Division of Oncology, Fiorini Hospital , Terracina , Italy Background The incorporation of docetaxel into the cisplatin and fluorouracil backbone has been demonstrated to be an active combination in metastatic gastric cancer. Nevertheless, this regimen is burdened by nonnegligible toxicity. We hypothesized that replacing cisplatin and fluorouracil with oxaliplatin and capecitabine should be an active and safe option for metastatic gastric cancer patients. Methods In this phase II study, we tested the activity of docetaxel in combination with oxaliplatin and capecitabine (DOC) as a first-line treatment. DOC was administered as follows: docetaxel (60 mg/m2) and oxaliplatin (100 mg/ m2) on day 1, and capecitabine (500 mg/m2) was administered orally twice daily given continuously, with cycles repeated every 3 weeks. The primary endpoint was the overall response rate. Results Forty-eight patients entered the study. All patients had metastatic disease (stage IV). None of the The present study has been presented in part in abstract form at the 2013 ASCO Annual Meeting (abstract 15065), Chicago, IL, May 31June 4. Capecitabine; Gastric cancer; Phase II; Docetaxel; Oxaliplatin - patients had previously received chemotherapy for advanced disease. Performance status was 0, 1, and 2 in 25, 58, and 17 % of patients, respectively; 13 patients (27 %) had adenocarcinoma of the gastroesophageal junction, and 29 patients (60.5 %) had two or more metastatic sites. The overall response rate was 52.1 %. Progression-free survival and overall survival were 6.9 and 12.6 months, respectively. The treatment was well tolerated with no treatmentrelated deaths. The most common grade 3–4 toxicity was neutropenia (41 %). Conclusions DOC is an effective and tolerated first-line treatment, and the lower dose of docetaxel and oxaliplatin used in this study compared with other similar regimens does not seem to hamper the antitumor activity. Introduction Gastric cancer is the fourth most common cancer worldwide and the second leading cause of cancer-related death [ 1 ]. The overall outlook for patients with gastric cancer is still dismal, as the majority are diagnosed with locally advanced or metastatic disease with a median survival of 7–10 months [ 2 ]. Pioneering randomized clinical trials demonstrated the superiority of palliative chemotherapy over best supportive care alone, with an improvement in survival and in quality of life (QoL) [ 3–5 ]. The role of chemotherapy was further confirmed in a meta-analysis, which also suggested that three-drug combinations conferred longer survival compared to monochemotherapy and doublets [ 6 ]. Nevertheless, there is no accepted standard regimen for advanced gastric cancer. In Europe, the combinations of epirubicin, cisplatin, and fluorouracil (ECF) and epirubicin, oxaliplatin, and capecitabine (EOX) have been considered as reference regimens [ 7 ]. In the United States the combination of docetaxel, cisplatin, and fluorouracil (DCF) is commonly used [ 8 ], whereas in Japan cisplatin with S1 has recently entered the therapeutic scenario [ 9 ]. During the past few years platinum salts, docetaxel, and trastuzumab have entered the therapeutic arena, demonstrating improved outcomes in randomized trials with a superiority design [ 10–12 ]. The incorporation of docetaxel to cisplatin/fluorouracil chemotherapy (DCF) showed superiority over cisplatin/fluorouracil in a randomized phase III trial [ 8 ]. Furthermore, in a recent meta-analysis the use of DCF was correlated with a higher response rate than non-taxanes-containing regimens [ 13 ]. Nevertheless, the widespread use of DCF was hindered by severe toxicity, such as neutropenic infections and febrile neutropenia. Evidence of docetaxel activity together with (...truncated)