Bevacizumab combined with docetaxel, oxaliplatin, and capecitabine, followed by maintenance with capecitabine and bevacizumab, as first-line treatment of patients with advanced HER2-negative gastric cancer: A multicenter phase 2 study
| Autor: | Meulendijks, Didier, De Groot, Jan Willem B, Los, Maartje, Boers, James E., Beerepoot, Laurens V., Polee, Marco B., Beeker, Aart, Portielje, Johanna E A, Goey, Swan H., De Jong, Robert S., Vanhoutvin, Steven A L W, Kuiper, Maria, Sikorska, Karolina, Pluim, Dick, Beijnen, Jos H., Schellens, Jan H M, Grootscholten, Cecile, Tesselaar, Margot E T, Cats, Annemieke, Sub Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology Cancer Research medicine.medical_specialty Organoplatinum Compounds Bevacizumab Receptor ErbB-2 Phases of clinical research Antineoplastic Agents Docetaxel Neutropenia Drug Administration Schedule Capecitabine 03 medical and health sciences 0302 clinical medicine Leukocytopenia Stomach Neoplasms Internal medicine Antineoplastic Combined Chemotherapy Protocols Humans Medicine Prospective Studies Methylenetetrahydrofolate Reductase (NADPH2) Aged business.industry gastric cancer clinical trial Middle Aged Neoplastic Cells Circulating medicine.disease Oxaliplatin Regimen 030104 developmental biology phase 2 030220 oncology & carcinogenesis Female Taxoids business medicine.drug |
| Zdroj: | Cancer, 122(9), 1434. John Wiley and Sons Inc. |
| ISSN: | 0008-543X |
| DOI: | 10.1002/cncr.29864 |
| Popis: | The current study was a multicenter, single-arm, phase 2 study performed to investigate the feasibility and efficacy of bevacizumab combined with docetaxel, oxaliplatin, and capecitabine (B-DOC) in patients with advanced human epidermal growth factor receptor 2 (HER2)-negative, previously untreated, gastric or gastroesophageal adenocarcinoma.Tumor HER2 status was determined centrally. Patients received 6 cycles of bevacizumab at a dose of 7.5 mg/kg, docetaxel at a dose of 50 mg/m(2) , and oxaliplatin at a dose of 100 mg/m(2) (all on day 1) combined with capecitabine at a dose of 850 mg/m(2) twice daily (days 1-14) every 3 weeks followed by maintenance with capecitabine and bevacizumab in patients with disease control. The primary objective was to demonstrate a progression-free survival (PFS) of6.5 months, according to the 95% confidence interval (95% CI). Secondary endpoints included safety, objective response rate, overall survival (OS), analyses of circulating tumor cells (CTCs), and pharmacogenetic analyses.Sixty eligible patients were enrolled. The median PFS was 8.3 months (95% CI, 7.2-10.9 months). The objective response rate was 70% (95% CI, 55%-83%) and the disease control rate was 96% (95% CI, 85%-99%). The median OS was 12.0 months (95% CI, 10.2-16.1 months). According to CTC-AE v4.0, the most common treatment-related grade ≥3 adverse events were neutropenia (20%), leukocytopenia (18%), diarrhea (15%), and nausea/vomiting (15%). The presence of CTCs at baseline was strongly predictive of PFS (hazard ratio [HR], 3.8; P =.007) and OS (HR, 3.4; P =.014). The methylenetetrahydrofolate reductase (MTHFR) 677CT genotype was strongly associated with PFS (HR, 4.7 for TT vs CC or CT; P =.0007) and OS (HR, 5.9; P =.0001).The B-DOC regimen plus maintenance was feasible and active. CTCs were found to be prognostic in patients treated with B-DOC. Docetaxel-based triplet chemotherapy as a backbone for targeted therapies is feasible and deserves further study. Cancer 2016;122:1434-1443. © 2016 American Cancer Society. |
| Databáze: | OpenAIRE |
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