Phase II study of fixed dose rate gemcitabine with cisplatin for metastatic adenocarcinoma of the pancreas

J Clin Oncol. 2006 Jan 20;24(3):379-85. doi: 10.1200/JCO.2005.01.8267. Epub 2005 Dec 12.

Abstract

Purpose: Although gemcitabine remains the standard of care for patients with advanced pancreatic cancer, additional improvements may be realized by combining therapeutic agents with synergistic activity, and optimizing drug delivery using pharmacokinetic principles such as fixed dose rate (FDR) infusion. The objectives of this study were to determine safety and efficacy in patients with metastatic pancreatic cancer treated with FDR gemcitabine in combination with low-dose cisplatin.

Patients and methods: Chemotherapy-naive patients with metastatic pancreatic adenocarcinoma were treated with a combination of gemcitabine 1,000 mg/m2 at 10 mg/m2/min together with cisplatin 20 mg/m2 on days 1 and 8 of a 21-day cycle. Patient follow-up was performed using computerized tomographic scans and serial CA 19-9 measurements.

Results: A total of 51 patients were enrolled onto the study, with a median follow-up time of 215 days. Twenty-two of 40 patients (55.0%) with a baseline serum CA 19-9 level > or = 2x the upper limit of normal demonstrated a > or = 50% biomarker decline during treatment. Nine of 47 patients (19.1%) with measurable disease achieved a partial response, and 28 patients (59.6%) had disease stabilization for at least two treatment cycles. Median time to progression was 3.9 months and median survival was 7.1 months, with an estimated 1-year survival rate of 29%. The most frequently reported grade 3 or 4 adverse events were neutropenia (52.9%) and thrombocytopenia (15.7%). Most patients were switched to an every-other-week dosing schedule.

Conclusion: The combination of FDR gemcitabine and cisplatin is well tolerated and appears to be an acceptable, albeit not clearly superior, alternative to other gemcitabine/platinum regimens for the treatment of metastatic pancreatic cancer.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / ethnology
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • CA-19-9 Antigen / blood
  • Cisplatin / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Disease Progression
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / ethnology
  • Research Design
  • Survival Analysis
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • CA-19-9 Antigen
  • Deoxycytidine
  • Cisplatin
  • Gemcitabine