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Int J Radiat Oncol Biol Phys. 2008 Jun 1;71(2):407-13. doi: 10.1016/j.ijrobp.2007.10.011. Epub 2007 Dec 31.

Toxicity profile and pharmacokinetic study of a phase I low-dose schedule-dependent radiosensitizing paclitaxel chemoradiation regimen for inoperable non-small-cell lung cancer.

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Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.



We report the toxicity profile and pharmacokinetic data of a schedule-dependent chemoradiation regimen using pulsed low-dose paclitaxel for radiosensitization in a Phase I study for inoperable non-small-cell lung cancer.


Paclitaxel at escalating doses of 15 mg/m(2), 20 mg/m(2), and 25 mg/m(2) were infused on Monday, Wednesday, and Friday with daily chest radiation in cohorts of 6 patients. Daily radiation was delayed for maximal G2/M arrest and apoptotic effect, an observation from preclinical investigations. Plasma paclitaxel concentration was determined by high-performance liquid chromatography.


Dose-limiting toxicities included 3 of 18 patients with Grade 3 pneumonitis and 3 of 18 patients with Grade 3 esophagitis. There was no Grade 4 or 5 pneumonitis or esophagitis. There was also no Grade 3 or 4 neutropenia, thrombocytopenia, anemia or neuropathy. For Dose Levels I (15 mg/m(2)), II (20 mg/m(2)), and III (25 mg/m(2)), the mean peak plasma level was 0.23 +/- 0.06 micromol/l, 0.32 +/- 0.05 micromol/l, and 0.52 +/- 0.14 micromol/l, respectively; AUC was 0.44 +/- 0.09 micromol/l, 0.61 +/- 0.1 micromol/l, and 0.96 +/- 0.23 micromol/l, respectively; and duration of drug concentration >0.05 micromol/l (t > 0.05 micromol/l) was 1.6 +/- 0.3 h, 1.9 +/- 0.2 h, and 3.0 +/- 0.9 h, respectively.


Pulsed low-dose paclitaxel chemoradiation is associated with low toxicity. Pharmacokinetic data showed that plasma paclitaxel concentration >0.05 micromol/l for a minimum of 1.6 h was sufficient for effective radiosensitization.

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