Concurrent chemoradiotherapy with gemcitabine and cisplatin for pancreatic cancer: from the laboratory to the clinic

Int J Radiat Oncol Biol Phys. 2002 May 1;53(1):140-5. doi: 10.1016/s0360-3016(01)02790-0.

Abstract

Purpose: We have reported that gemcitabine and concurrent radiation is a promising therapy for patients with pancreatic cancer. We investigated whether the addition of cisplatin, which may increase the systemic efficacy of gemcitabine, would be synergistic with gemcitabine and/or radiation in human pancreatic cancer cell lines.

Methods and materials: BxPc3 and Panc-1 human pancreatic cancer cells were treated with three different schedules before radiation: (A) a sequential incubation of gemcitabine for 2 h followed by cisplatin for 2 h, (B) gemcitabine for 2 h, followed by washout of drug, replenishment of media for a 24-h incubation, followed by cisplatin for 2 h, and (C) gemcitabine for 24 h with a concurrent incubation of cisplatin for the last 2 h. Cells were assessed for clonogenic survival using a standard assay. Synergism was evaluated by the median effect analysis.

Results: The schedule shown to be maximally synergistic for both cell lines was the consecutive 2-h gemcitabine, 2-h cisplatin exposure, particularly at surviving fractions of <0.5. Cisplatin did not produce radiosensitization nor did it affect gemcitabine-mediated radiosensitization.

Conclusion: Cisplatin produces synergistic cytotoxicity with gemcitabine without compromising gemcitabine-mediated radiosensitization. On the basis of these laboratory and previous clinical observations, we have initiated a Phase I trial of cisplatin plus gemcitabine and radiotherapy in patients with unresectable pancreatic cancer.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Humans
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / radiotherapy*
  • Radiation-Sensitizing Agents / therapeutic use*
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / radiation effects

Substances

  • Radiation-Sensitizing Agents
  • Deoxycytidine
  • gemcitabine
  • Cisplatin