Evaluation of low-dose fractionated radiation therapy as a chemopotentiator of gemcitabine in advanced pancreatic cancer: results from an international multi-institutional phase II trial

Autor: Pierre Major, Nancy L. Kennedy, H. Richard Alexander, Daniel A. Laheru, Joseph M. Herman, Raimond Wong, Naimish Pandya, Navesh K. Sharma, William F. Regine, Nader Hanna
Rok vydání: 2015
Předmět:
Zdroj: Journal of Radiation Oncology. 4:401-409
ISSN: 1948-7908
1948-7894
DOI: 10.1007/s13566-015-0213-8
Popis: Potentiation of systemic dosing of gemcitabine using very low-dose fractionated radiotherapy may improve its effect in advanced pancreatic cancer without additional toxicity as suggested by the results of our multi-institutional phase II study. Future regimens combining low-dose fractionated radiotherapy (RT) with systemic chemotherapy should be assessed for improving the chemotherapeutic benefit. Until recently, gemcitabine was considered the standard treatment for advanced pancreatic cancer despite low response rates. Efforts to improve response rates by combination therapies have had limited success and have involved using sub-systemic dosing of gemcitabine as a sensitizer for radiation. A novel paradigm, utilizing low-dose fractionated radiotherapy (LDFRT) as a potentiator of full-dose gemcitabine instead, was explored to assess safety and efficacy in treating advanced pancreatic cancer. Patients with locally advanced and metastatic pancreatic cancer were treated with 4 cycles of gemcitabine and LDFRT in a multi-institutional phase II study. Gemcitabine (1250 mg/m2 over 2 h) was administered on days 1 and 8 of a 21-day cycle. LDFRT fields included the upper abdomen from the diaphragm to the iliac crest and were administered at 60 cGy per fraction twice daily on days 1, 2, 8, and 9, with the morning fraction being delivered prior to gemcitabine infusion on days 1 and 8. Primary endpoint was objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST). Thirty-eight patients were enrolled in the trial, of which 23 had metastatic disease at time of enrollment. Objective response rate (CR + PR) was 8 %, and 61 % had at least stable disease. Overall median survival was 13 months and 1-year survival was 37 %. Patients with non-metastatic disease had a 1-year survival of 60 %. The most significant toxicity was hematologic, and only 3 patients were withdrawn from protocol due to toxicity. There was no reported febrile neutropenia. The use of LDFRT with systemic gemcitabine is safe, tolerable, and potentially effective. In advanced pancreatic cancer, where response rates with single-agent gemcitabine have been low, this chemopotentiation paradigm may improve survival among a poor prognostic patient cohort.
Databáze: OpenAIRE
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