Evaluation of gemcitabine efficacy after the FOLFIRINOX regimen in patients with advanced pancreatic adenocarcinoma.

To evaluate gemcitabine efficacy in advanced pancreatic cancer patients after the FOLFIRINOX regimen.Patients with locally-advanced or metastatic pancreatic adenocarcinoma from French and Canadian centers, who were treated with the first-line FOLFIRINOX regimen (FFX L1), followed by gemcitabine monotherapy as a second-line treatment (GEM L2), were retrospectively evaluated. Statistical analyses were performed on the demographic, toxicity, and response rate data. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method.Seventy-two patients were reviewed (median age of 63.5 years [range, 32-75 years], men [62%], predominantly pancreatic head tumor location [51%] and metastatic disease [64%] at the time of diagnosis). The objective response rate to GEM-L2 treatment was 8/72 (11%), and 32 patients (44%) experienced a clinical benefit from gemcitabine. Four patients had a partial response to GEM-L2, although they previously showed a progressive response following FFX-L1 treatment. The median OS for the entire cohort was 13.6 months (95% confidence interval [CI]: 2.0-35). The median PFS of the GEM-L2 group was 2.5 months (95% CI: 0.2-10.8) with no statistical differences between patients with controlled or progressive disease on FFX-L1 therapy.Gemcitabine as a second-line treatment for advanced pancreatic adenocarcinoma after FOLFIRINOX failure showed clinical benefits in some patients.

Phase I and pharmacokinetic study of escalating dose of docetaxel administered with granulocyte colony-stimulating factor support in adult advanced solid tumors.

PURPOSE: The purpose of our study was to assess the feasibility, toxicity, and pharmacokinetics of an escalating dose of docetaxel when administered with granulocyte colony-stimulating factor (G-CSF) support every 3 weeks. EXPERIMENTAL DESIGN: Patients with advanced solid malignancies were treated with escalating doses of docetaxel as a 1-h infusion every 3 weeks, supported by s.c. administration of human recombinant glycosilated G-CSF Granocyte (lenograstim), 5 microg/kg/day (from day 4 until neutrophil count >0.5-10(g)/liter for two consecutive days). Plasma sampling was performed to characterize the pharmacokinetics of docetaxel at the new recommended high-dose level. RESULTS: Forty-seven patients were treated with 116 courses of docetaxel at eight dose levels ranging from 100-185 mg/m(2). Dose-limiting toxicities were nonhematologic and included mucositis and dermatitis. Severe skin toxicity observed at 185 mg/m(2) led to discontinuing the study, and 175 mg/m(2) was selected as the recommended dose of docetaxel + G-CSF for future Phase II studies. Analysis of multiple courses revealed dermatitis, mucositis, arthralgia/myalgia, and neuropathy as the main dose-related toxic events. At 175 mg/m(2) mean +/- SD values for docetaxel plasmatic peak, area under the curve, clearance, volume of distribution, and terminal half-life were 6.7 +/- 1.7 microg/ml, 9.7 +/- 4 microg.h/ml, 34.2 +/- 12 liters/h, and 122.7 +/- 124 liters, respectively. Of the 16 patients treated at 175 mg/m(2), 8 patients responded (7 breast cancer and 1 lung cancer patients) including one complete response (1 breast cancer patient). CONCLUSIONS: Using G-CSF support allows substantial dose escalation of docetaxel. Whether such a dose increase improves the response rate warrants further investigation. At the highest dose level studied, pharmacokinetic parameters seem to maintain a linear profile.