Simultaneous Gemcitabine/Cisplatin and Radiotherapy for Patients with Locally Advanced Pancreatic Adenocarcinoma using a Strict GEM/RT Time Schedule. A Phase I/II Study

Diana Stripp, MD
University of Pennsylvania Cancer Center
Last Modified: November 5, 2001

Presenter: T. Brunner
Presenter's Affiliation: University Hospitals Erlangen, Erlangen, Germany
Type of Session: Scientific


  • Patients with locally advanced pancreatic cancer treated with induction chemoradiation (CRT) prior to surgery have a survival advantage as compared to patients treated with resection at diagnosis. Snady et al. (Cancer 2000)
  • Gemcitabine (GEM) and cisplatin (cDDP) individually are radiosensitizers and have activity in pancreatic cancer.
  • Experimental studies and clinical data suggest that (1) response of pancreatic cancer to GEM/cDDP is better than GEM alone, (2) normal tissues recover more quickly than tumor tissues from GEM&RT and (3) enhancement of tumor radioresponsivness lasts at least 72 h after GEM.
  • This study aimed to evaluate the feasibility and the efficacy at the recommended dose level of gemcitabine (GEM)/ cisplatin (cDDP) with RT

    Materials and Methods

  • 33 patients with locally advanced pancreatic cancer and peripancreatic vessel involvement (VI), periampullary carcinoma (1 pt), and cancer of the biliary system (2 pts) have been enrolled.
  • 3D-conformal RT was prescribed to the involved field and lymphatics concomitantly with cDDP at 20 mg/m2/d (I.V. bolus 20') on days 1-5, 29-33 and GEM (I.V. bolus 30') was administered at 5 dose levels (DL).
  • Patients received radiation to a dose of 50.4 Gy plus a 5.4 Gy boost
  • To avoid sensitization of normal tissue, GEM was administered consistently on Fridays 6 h after RT.
  • Dose limiting toxicity (DLT) was defined as grade 4 toxicity.


  • Non-hematologic toxicity was relatively mild with 5 pts developing grade 3 nausea/vomiting and 1 patient developing grade 3 diarrhea
  • 1 patient at dose level 1 who died 4.5 months after completion of therapy from duodenal ulcer bleeding regarded as DLT.
  • 9 of 20 (45 %) initially unresectable patients with pancreatic cancer but vessel involvement were resectable 6 weeks after chemoradiation.
  • Reasons against resection were: continued vessel involvement (8 pts), liver metastasis (3 pts), peritoneal seeding (1 pt), refusal of resection (1 pt).

    Author's Conclusions

  • Toxicity is pronounced at higher dose levels with one lethal late GI bleeding and non-lethal grade 4 hematotoxicity.
  • The maximal tolerated dose in this combined modality schedule was 400 mg/m2 and the dose level of 300 mg/m2 was deemed to be safe and used for the ongoing phase II study.
  • Response was good with a significant downstaging in 9/20 pts (45 %) entering the neoadjuvant treatment group.

    Clinical/Scientific Implications

  • Increased toxicity of chemoradiation with gemcitabine is dose related.
  • Use of gemcitabine as a XRT sensitizer should be only consider under investigational settings until further data is available with the use of this potent XRT sensitizer

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