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

James A. Martenson, Antonio P G Vigliotti, Henry Clement Pitot, Louis H. Geeraerts, Daniel J. Sargent, Michael Haddock, Chirantan Ghosh, Michael D. Keppen, Tom R. Fitch, Richard M. Goldberg, Roberta Schwartz

Research output: Contribution to journalArticle

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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/m2 i.v. The starting dose for cisplatin was 5 mg/m2. 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/m2 i.v. and cisplatin 10 mg/m2 i.v.). Six patients were treated at dose Level 5 (gemcitabine 30 mg/m2 i.v. and cisplatin 10 mg/m2 i.v.) without dose-limiting toxicity. Conclusion: Gemcitabine 30 mg/m2 i.v. twice weekly and cisplatin 10 mg/m2 i.v. twice weekly may be given concurrently with radiation therapy (50.4 Gy in 28 fractions) with acceptable toxicity.

Original languageEnglish (US)
Pages (from-to)1305-1310
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Volume55
Issue number5
DOIs
StatePublished - Apr 1 2003

Fingerprint

gemcitabine
Pancreatic Neoplasms
Cisplatin
radiation therapy
Radiotherapy
cancer
dosage
toxicity
grade
vomiting
nausea
chemotherapy
Nausea
Vomiting
Radiation-Sensitizing Agents
Drug Therapy
Lymphopenia
Poisons
Radiation Effects
Neutropenia

Keywords

  • Cisplatin
  • Gemcitabine
  • Pancreatic cancer
  • Radiation therapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

A phase I study of radiation therapy and twice-weekly gemcitabine and cisplatin in patients with locally advanced pancreatic cancer. / Martenson, James A.; Vigliotti, Antonio P G; Pitot, Henry Clement; Geeraerts, Louis H.; Sargent, Daniel J.; Haddock, Michael; Ghosh, Chirantan; Keppen, Michael D.; Fitch, Tom R.; Goldberg, Richard M.; Schwartz, Roberta.

In: International Journal of Radiation Oncology Biology Physics, Vol. 55, No. 5, 01.04.2003, p. 1305-1310.

Research output: Contribution to journalArticle

Martenson, James A. ; Vigliotti, Antonio P G ; Pitot, Henry Clement ; Geeraerts, Louis H. ; Sargent, Daniel J. ; Haddock, Michael ; Ghosh, Chirantan ; Keppen, Michael D. ; Fitch, Tom R. ; Goldberg, Richard M. ; Schwartz, Roberta. / A phase I study of radiation therapy and twice-weekly gemcitabine and cisplatin in patients with locally advanced pancreatic cancer. In: International Journal of Radiation Oncology Biology Physics. 2003 ; Vol. 55, No. 5. pp. 1305-1310.
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AU - Pitot, Henry Clement

AU - Geeraerts, Louis H.

AU - Sargent, Daniel J.

AU - Haddock, Michael

AU - Ghosh, Chirantan

AU - Keppen, Michael D.

AU - Fitch, Tom R.

AU - Goldberg, Richard M.

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