Fludarabine combined with radiotherapy in patients with locally advanced NSCLC lung carcinoma: a phase I study.

Abstract

BACKGROUND AND PURPOSE:

Fludarabine is an adenine nucleoside analogue that has significant activity in hematological malignancies and has shown promising activity in combination with radiation in preclinical solid tumor models. We designed a phase I trial exploring concurrent fludarabine and radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) to determine the maximum tolerated dose (MTD) of fludarabine given with concurrent irradiation.

MATERIALS AND METHODS:

Thirteen patients with stage IIIB NSCLC received thoracic irradiation of 60 Gy. Fludarabine was administered during the 5th and 6th week of radiotherapy. Doses started at 10 mg/m(2) per day and increased by steps of 3 mg/m(2) per day.

RESULTS:

At a daily dose of 16 mg/m(2), one out of six patients developed a grade 4 leukopenia, and one a grad 3 pneumonitis. Further grade III toxicity was not observed. The dose of 13 mg/m(2) was identified as the MTD. All patients developed a fludarabine dose-dependent lymphocytopenia.

CONCLUSION:

Fludarabine can be safely administered concurrently with radiation at a daily dose of 13 mg/m(2) during the final 2 weeks of radiotherapy. Further prospective clinical studies are required to establish the potential role of concurrent fludarabine and radiotherapy in the treatment of locally advanced inoperable NSCLC.

• Authors: Mirko Nitsche, Hans Christiansen, Katinka Lederer, Frank Griesinger, Heinz Schmidberger, Olivier Pradier
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 138 Issue 7 Pg. 1113-20 (Jul 2012) ISSN: 1432-1335 [Electronic] Germany
• PMID: 22402597 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Antineoplastic Agents
• Radiation-Sensitizing Agents
• Vidarabine
• fludarabine

Topics

• Antineoplastic Agents (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology, radiotherapy)
• Combined Modality Therapy
• Humans
• Lung Neoplasms (drug therapy, pathology, radiotherapy)
• Neoplasm Staging
• Radiation-Sensitizing Agents (therapeutic use)
• Radiotherapy Dosage
• Vidarabine (analogs & derivatives, therapeutic use)