Weekly gemcitabine and 24-hour infusional 5-fluorouracil in advanced pancreatic cancer: a phase I-II study.

OBJECTIVE: In this phase I-II study we explored the potential of the combination of weekly gemcitabine (GEM) and 24-hour continuous infusion of 5-fluorouracil (5-FU) in order to determine the toxicity profile in pancreatic cancer. The efficacy of this drug combination was studied as a secondary endpoint. METHODS: Twenty-one patients with histologically or cytologically proven unresectable or metastatic previously untreated pancreatic adenocarcinoma were included in this study. Two dose levels of GEM and two dose levels of 5-FU were evaluated in three cohorts of patients who received GEM 1,000 mg/m(2) and 5-FU 2,000 mg/m(2), GEM 1,200 mg/m(2) and 5-FU 2,000 mg/m(2), or GEM 1,200 mg/m(2) and 5-FU 2,250 mg/m(2), on days 1, 8, and 15, every 4 weeks, respectively. RESULTS: Grade 3-4 neutropenia was observed in 10% of the cycles. Non-myelosuppressive toxicities included fatigue (22%), grade 1-2 diarrhea (12%) and grade 1 liver toxicity. There was no limiting toxicity and the maximum tolerated dose has not been reached. Two patients experienced a partial response (9.5 +/- 12.6%) and 12 patients had stable disease (57.1 +/- 21.2%). Seven of the 14 symptomatic patients improved their disease-related symptoms and 4 of the 8 patients evaluable for clinical benefit had a clinically beneficial response (50 +/- 34.6%). The median progression-free survival was 6 months (range 2-28), median survival was 11 months (range 3-32+), and the actuarial 1-year survival rate 33%. CONCLUSION: The weekly administration of GEM combined with 24-hour continuous infusion of 5-FU shows a good safety profile at the dose levels evaluated. Some partial responses had also been achieved, disregarding the dose level of the two drugs. Survival confirms the activity of this drug combination.

Valved central venous catheter connected to subcutaneous port: A multicenter phase IV study based on a cohort of 50 oncology patients.

PURPOSE: Since technical aspects and clinical features of central venous valved catheters are far from being completely understood, a multinational group of investigators has decided to assess a new distally-valved catheter connected to a port, in the clinical setting of oncology patients undergoing chemotherapy, in an attempt to verify its safety and viability, while also investigating its practical features. METHODS: Our project was structured as a phase IV multicenter study. Hospitalized adults (ages 18-80 years) who had solid tumors and were candidate for intravenous chemotherapy met the criteria to enter the study. One single type of port was used (made of titanium, plastic and silicone) connected to a silicone, distally valved catheter (as manufactured by B. Braun Aesculap). A case report form was provided for each treated case; all relevant data regarding implantation and follow-up were entered into the form, mailed to a coordinating center (G. Chevillon, B. Braun Medical, France) and stored in a software database for statistical analysis. RESULTS: 50 patients (from 6 participating centers) were included in this study. No major complications occurred at insertion. The most frequent clinical problem during follow-up was inability to draw blood samples (9% during the first chemotherapy cycle; 8% after the second cycle); blood obtained from the device was defined 'unsuitable for hematology test' in 9% of the cases at first chemotherapy cycle and in 23% of the cases after the second cycle. No catheter obstruction occurred. CONCLUSION: The distally valved catheter port tested in this study was reliable, safe and practical for long-term treatment of an oncology patients' population undergoing chemotherapy. As most other reports and clinical trials dealing with other types of distally valved catheters pointed out, inability to draw viable blood samples (so called withdrawal occlusion) is a major concern in their clinical use. Mechanisms underlying this technical problem are still unclear.