ABSTRACT
BACKGROUND: There is no standard second-line therapy for advanced pancreatic cancer (APC). We evaluated the epidermal growth factor receptor (EGFR) inhibitor gefitinib and docetaxel in a phase II study following gemcitabine failure. METHODS: EGFR overexpression was not required. The initial docetaxel dose was 75 mg/m(2) on day 1 every 21 days. Due to febrile neutropenia in 8 of the first 18 patients, the dose was reduced to 60 mg/m(2). Gefitinib, 250 mg/day orally, was given continuously. RESULTS: Forty-one patients received treatment and were evaluable. Febrile neutropenia was seen in 11 patients (27%), with most events occurring at the docetaxel dose of 75 mg/m(2) (8 of 18 patients). Common treatment-related grade 3/4 toxicities were: fatigue (7%), nausea (7%), diarrhea (5%) and vomiting (2%). There was 1 partial response and stable disease in 19 patients. Time to progression was 1.8 months and median survival was 4.5 months (95% CI 2.9-5.7). CONCLUSION: The tolerability and feasibility of second-line therapy for APC was demonstrated. The combination of gefitinib and docetaxel showed evidence of limited efficacy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pancreatic Neoplasms/drug therapy , Aged , Aged, 80 and over , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Docetaxel , Female , Gefitinib , Humans , Male , Middle Aged , Pancreatic Neoplasms/mortality , Quinazolines/administration & dosage , Quinazolines/adverse effects , Taxoids/administration & dosage , Taxoids/adverse effects , GemcitabineABSTRACT
OBJECTIVE: We tested the hypothesis that the combination of trimetrexate (TMTX) and capecitabine (CAP) would be active in patients with previously treated metastatic colorectal cancer (CRC). Because the optimum dose of this combination was unknown, we used a phase I/II design. METHODS: In the phase I cohort, patients received 110 mg/m2 TMTX intravenously weekly x6 and CAP starting at 750 mg/m2 orally twice daily from days 2 to 15 and 23 to 36 (one cycle). Cycles were repeated every 8 weeks. The phase II doses were 110 mg/m2 TMTX and 1000 mg/m2 CAP orally twice daily. RESULTS: Thirty-two patients were entered. All patients had prior 5-fluorouracil therapy and 94% had prior exposure to irinotecan. Grade 3/4 toxicities included abdominal pain in 4 patients (12.5%) and vomiting in 3 patients (9.4%). Twenty-seven patients were evaluable for response: one patient each had a complete response and a partial response for an overall response rate of 7.4%. The median time to progression was 3.3 months (95% confidence interval [CI], 1.6-3.7 months) and the median overall survival was 5.9 months (95% CI, 5.2-10.2 months). CONCLUSIONS: The combination of TMTX and CAP is well tolerated. However, recent studies have shown more active regimens in the second- and third-line metastatic setting.
