A phase I study of radiation therapy and twice-weekly gemcitabine and cisplatin in patients with locally advanced pancreatic cancer.

Abstract

PURPOSE:

In vitro studies suggest that low-dose gemcitabine sensitizes cells to radiation therapy and that this effect persists for 48 h after drug exposure. Cisplatin is a radiation sensitizer and is also synergistic with gemcitabine in some in vitro tumor systems. Gemcitabine's radiosensitizing properties can theoretically be exploited by twice-weekly administration. This study assessed toxicity in patients with pancreatic cancer treated with radiation therapy, gemcitabine, and cisplatin.

METHODS AND MATERIALS:

Patients with locally advanced pancreatic or gastric cancer were eligible. Gemcitabine and cisplatin were given twice weekly for 3 weeks during radiation therapy (50.4 Gy in 28 fractions). The starting dose of gemcitabine was 5 mg/m(2) i.v. The starting dose for cisplatin was 5 mg/m(2). Chemotherapy doses escalated every 3 to 6 patients according to a standard Phase I study design.

RESULTS:

Twenty-four evaluable patients, all with pancreatic cancer, were treated on this protocol. Grade 3 neutropenia occurred in 2 patients, Grade 3 thrombocytopenia occurred in 2, and Grade 4 lymphopenia occurred in 1. There was no clear relationship between chemotherapy dose and hematologic toxicity. The most common Grade 3-4 nonhematologic toxic responses were vomiting (7 patients) and nausea (7 patients). Dose-limiting toxicity consisting of Grade 4 nausea and vomiting occurred in 2 of 3 patients at dose Level 6 (gemcitabine 45 mg/m(2) i.v. and cisplatin 10 mg/m(2) i.v.). Six patients were treated at dose Level 5 (gemcitabine 30 mg/m(2) i.v. and cisplatin 10 mg/m(2) i.v.) without dose-limiting toxicity.

CONCLUSION:

Gemcitabine 30 mg/m(2) i.v. twice weekly and cisplatin 10 mg/m(2) i.v. twice weekly may be given concurrently with radiation therapy (50.4 Gy in 28 fractions) with acceptable toxicity.

• Authors: James A Martenson, Antonio P G Vigliotti, Henry C Pitot, Louis H Geeraerts, Daniel J Sargent, Michael G Haddock, Chirantan Ghosh, Michael D Keppen, Tom R Fitch, Richard M Goldberg
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 55 Issue 5 Pg. 1305-10 (Apr 01 2003) ISSN: 0360-3016 [Print] United States
• PMID: 12654442 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Radiation-Sensitizing Agents
• Deoxycytidine
• Cisplatin
• Gemcitabine

Topics

• Adenocarcinoma (drug therapy, mortality, pathology, radiotherapy, surgery)
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chemotherapy, Adjuvant
• Cisplatin (administration & dosage)
• Combined Modality Therapy
• Deoxycytidine (administration & dosage, analogs & derivatives, pharmacology)
• Diarrhea (etiology)
• Drug Administration Schedule
• Female
• Hematologic Diseases (etiology)
• Humans
• Life Tables
• Male
• Maximum Tolerated Dose
• Middle Aged
• Nausea (etiology)
• Pancreatectomy
• Pancreatic Neoplasms (drug therapy, mortality, pathology, radiotherapy, surgery)
• Radiation-Sensitizing Agents (administration & dosage, pharmacology)
• Survival Analysis
• Treatment Outcome
• Vomiting (etiology)
• Gemcitabine