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 language | English (US) |
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Pages (from-to) | 1305-1310 |
Number of pages | 6 |
Journal | International Journal of Radiation Oncology Biology Physics |
Volume | 55 |
Issue number | 5 |
DOIs | |
State | Published - Apr 1 2003 |
Keywords
- Cisplatin
- Gemcitabine
- Pancreatic cancer
- Radiation therapy
ASJC Scopus subject areas
- Radiation
- Oncology
- Radiology Nuclear Medicine and imaging
- Cancer Research