A phase II trial of gemcitabine and weekly high-dose 5-fluorouracil in a 48-hour continuous-infusion schedule in patients with advanced pancreatic carcinoma. A study of the Spanish Cooperative Group for Gastrointestinal Tumour Therapy (TTD).

AIM: A multi-centred, open-labelled, phase 11 study containing 46 patients was conducted to evaluate the clinical benefit of gemcitabine (1,400 mg/m(2)) combined with 5-FU (3 g/m(2)) in a 48 h continuous infusion (CI). METHODS: Both drugs were administered on days 1, 8 and 15 of every 4 week cycle in chemotherapy-naïve patients with locally advanced unresectable metastatic pancreatic carcinoma. The minimum follow-up was 6 months. RESULTS: Clinical benefit response was the primary endpoint and this was achieved by 24.4% of the patients. Quality of life (QoL) improved in 16.6% of patients. Objective response was observed in 7% of the patients. The median progression-free survival (PFS) was 14.4 weeks and the median overall survival (OS) time was 22.7 weeks. One-year survival was 25%. The most frequent grade 3-4 toxicities were neutropenia (45%), mucositis (7.5%) and hyperbilirubinaemia (10.5%). CONCLUSIONS: This schedule was not superior in terms of clinical benefit, response rate, PFS and OS than standard gemcitabine treatment

Phase II trial of cetuximab in combination with fluorouracil, leucovorin, and oxaliplatin in the first-line treatment of metastatic colorectal cancer.

PURPOSE: This phase II study investigated the efficacy and safety of cetuximab combined with standard oxaliplatin-based chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin [FOLFOX-4]) in the first-line treatment of epidermal growth factor receptor-expressing metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: The activity of cetuximab plus oxaliplatin was investigated in colon cancer cell lines and xenograft models. In the clinical study, patients with mCRC received on day 1 of a 14 day cycle, cetuximab (initial dose 400 mg/m(2) during week 1, then 250 mg/m(2) weekly) followed by FOLFOX-4 (oxaliplatin 85 mg/m(2) on day 1; leucovorin 200 mg/m(2) on days 1 and 2, followed by fluorouracil 400 mg/m(2) bolus then 600 mg/m(2) intravenous infusion during 22 hours on days 1 and 2). RESULTS: The preclinical studies confirmed the supra-additive activity of cetuximab to oxaliplatin. In the clinical study, 43 patients were included, with a median age of 65 years (range, 43 to 78 years). Response rates (RRs) were 79% (unconfirmed) and 72% (confirmed), with 95% disease control. Median progression-free survival (mPFS) and median duration of response were 12.3 and 10.8 months, respectively. Ten patients (23%) underwent resection with curative intent of previously unresectable metastases. After a median follow-up of 30.5 months, median overall survival (mOS) was 30.0 months. Cetuximab did not increase the characteristic toxicity of FOLFOX-4 and was generally well tolerated. CONCLUSION: Cetuximab in combination with FOLFOX-4 is a highly active first-line treatment for mCRC, showing encouraging RR, mPFS, and mOS values. The treatment resulted in a high resectability rate, which could potentially result in an improved cure rate. This combination is under phase III development.