RESUMEN
OBJECTIVE: To evaluate the safety/tolerability and potential antitumor activity of lapatinib, at dose ranges of 1000 to 1500 mg/d, in combination with gemcitabine and gemcitabine/oxaliplatin (GEMOX) in patients with advanced pancreaticobiliary cancer. MATERIALS AND METHODS: Patients with advanced pancreaticobiliary cancer were assigned to 1 of 4 cohorts of lapatinib administered once daily. Toxicities, response, and survival were assessed. RESULTS: Twenty-five patients were enrolled, 18 with pancreatic cancer and 7 with biliary cancer. Lapatinib, 1500 mg/d, was successfully administered with weekly gemcitabine. Dose limiting toxicities of nausea and anorexia occurred in 2 of 5 patients receiving 1500 mg/d lapatinib with GEMOX. The median survival of all patients was 11 months and the 1-year survival was 48%. CONCLUSION: Lapatinib, 1500 mg/d, can be administered with weekly gemcitabine. The maximum tolerated dose of lapatinib is 1000 mg/d with GEMOX. A phase II study of lapatinib and gemcitabine for metastatic pancreatic cancer will be initiated.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de los Conductos Biliares/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Relación Dosis-Respuesta a Droga , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Lapatinib , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Neoplasias Pancreáticas/patología , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Piridinas/administración & dosificación , Piridinas/efectos adversos , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Análisis de Supervivencia , GemcitabinaRESUMEN
OBJECTIVES: Docetaxel, capecitabine, and oxaliplatin are important new agents in esophagogastric cancer. The Brown University Oncology Group initiated a phase I study to determine the maximum tolerated dose of weekly docetaxel, oxaliplatin, and capecitabine. METHODS: Patients with metastatic esophageal and gastric cancers received docetaxel and oxaliplatin on days 1 and 8 and capecitabine in divided doses, twice daily, on days 1 to 10, with each cycle repeated every 21 days. Patients were enrolled in cohorts of 3 at escalating dose levels. The docetaxel dose ranged from 30 to 35 mg/m2, the oxaliplatin dose from 40 to 50 mg/m2, and the capecitabine dose from 750 to 850 mg/m2 BID. RESULTS: Sixteen patients were enrolled over 4 dose levels. The median age was 59 years. Eight patients had esophageal cancer and 9 had gastric cancer. Grade 3/4 dose-limiting toxicities of diarrhea, nausea, fatigue, and febrile neutropenia occurred in 3 of 4 patients at dose level 3. An intermediate dose level was added (2A), reducing the capecitabine dose to 750 mg/m2. One of 6 patients had a dose-limiting toxicity at level 2A. CONCLUSIONS: Oxaliplatin 50 mg/m2 and docetaxel 30 mg/m2 day 1 and 8 with capecitabine 750 mg/m2 BID for 10 days in 21-day cycles may represent a promising, easily administered regimen for metastatic esophageal and gastric cancer. A phase II study will be initiated.