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
BackgroundPatients 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
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.
ResultsNon-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 ConclusionsToxicity 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 ImplicationsIncreased 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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