Abstract | BACKGROUND AND PURPOSE: MATERIALS AND METHODS:
Fludarabine was administered i.v. daily 3-4 h before the last 10 fractions of a standard radiation fractionation regimen (70 Gy in 7 weeks). The main objective of the trials was to determine the maximum tolerated dose (MTD) of fludarabine in this particular setting. Twenty-eight patients with stage T2-T4, any N, M0 were included in the study. Fludarabine doses started at 7.5 mg/m(2) per day (3 mg/m(2) per day in Houston) and increased by steps of 2.5 mg/m(2) per day (3 mg/m(2) per day in Houston). RESULTS: The addition of fludarabine at increasing doses to radiation did not result in increased intensity or duration of skin (18% grade 3 dermatitis) or mucosal (60% grade 3 mucositis) radiotoxicity compared to what was expected for radiation alone. At a daily dose of 17.5 mg/m(2), two patients out of five (40%) developed a grade 4 neutropenia, of whom one developed a neutropenic fever. This dose was set as the MTD. All patients developed a fludarabine dose-dependant lymphocytopenia. The plasma F-ara-A concentration peaked after the 30-min infusion in a dose-dependent fashion and reached an average peak concentration of approximately 2 microM for doses of 15 mg/m(2) and higher. CONCLUSIONS: This study demonstrates that fludarabine can be safely administered concurrently with radiation at a daily dose of 15 mg/m(2) during the final 2 weeks of radiotherapy. A phase II trial will be required to establish the potential role of concurrent fludarabine and radiotherapy in the treatment of moderately to locally advanced HNSCC.
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Authors | Vincent Grégoire, K Kian Ang, Jean-François Rosier, Marc Beauduin, Adam S Garden, Marc Hamoir, Walter N Hittelman, Yves Humblet, Fadlo R Khuri, Luka Milas, Carine Mitine, Pierre Scalliet |
Journal | Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
(Radiother Oncol)
Vol. 63
Issue 2
Pg. 187-93
(May 2002)
ISSN: 0167-8140 [Print] Ireland |
PMID | 12063008
(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.)
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Chemical References |
- Antineoplastic Agents
- Vidarabine
- fludarabine
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Agents
(adverse effects, pharmacokinetics, therapeutic use)
- Carcinoma, Squamous Cell
(drug therapy, radiotherapy)
- Combined Modality Therapy
- Female
- Humans
- Male
- Middle Aged
- Mouth Neoplasms
(drug therapy, radiotherapy)
- Otorhinolaryngologic Neoplasms
(drug therapy, radiotherapy)
- Radiation Injuries
- Vidarabine
(adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)
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