Gemcitabine, docetaxel, and capecitabine (GTX) in the treatment of metastatic pancreatic cancer (PC): A prospective phase II study

Abstract

14024 Background: We have found that the combination of gemcitabine, docetaxel, and capecitabine (GTX), when administered in a specific sequence, will induce a p53 independent pathway of cell death through the MAP kinase pathway. The sequence overcomes drug resistance in PC cells in vitro. We have begun a prospective, phase II trial of GTX in patients with metastatic PC as first-line therapy. Methods: 23 patients with metastatic PC, ECOG 0–2 were enrolled at either Columbia or a community practice. Each cycle was administered over a 21 days. Capecitabine was administered at 750 mg/m2 twice daily for 14 days. Gemcitabine (750 mg/m2 over 75 minutes) and docetaxel (30 mg/m2) were administered on days 4 and 11. Responses were measured by CT (RECIST) and PET after every three cycles. A response by PET was defined as a 50% reduction in SUV while a CR was an absence of uptake. Results: Median age was 61, including 8 men and 15 women. Metastatic sites included liver (87%), abdomen (65%), and lung (17%). 70% of liver positive patients had at least five metastases. 22% had malignant ascites. 16 patients remain alive and 7 have progressive disease. Median survival has not yet been reached. Progression occurred at a median of 5.1 months. By CT, the response rate at metastatic sites was 39% (17% CR / 22% PR). Stable disease was observed in 48% at metastatic sites. PET showed a 53% response rate at metastatic sites. At the primary site, CT showed a 30% response rate including 17% complete responses. By PET criteria, there was a 31% response rate and a 26% CR rate at the primary site. In three patients, a PET response heralded a CT response by three cycles. In one patient, progressive disease on PET preceded progression on CT by two months. Toxicity: Grade 3 leukopenia and thrombocytopenia were 13% and 9%, respectively. There was no grade four hematologic toxicity. One patient experienced lung disease related to gemcitabine and withdrew from the study. A second patient experienced grade 4 mucositis, thrush, and sepsis which was presumed due to DPD deficiency. Grade 3–4 toxicities: HFS: 9%. There was no grade 3–4 diarrhea. Conclusions: GTX, elicits a promising response rate when used in metastatic P.C. PET detects a response and failure of chemotherapy earlier than CT scans. [Table: see text]