Toxicity profile and pharmacokinetic study of a phase I low-dose schedule-dependent radiosensitizing paclitaxel chemoradiation regimen for inoperable non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2008 Jun 01;71(2):407-13
Date
01/01/2008Pubmed ID
18164866Pubmed Central ID
PMC2771614DOI
10.1016/j.ijrobp.2007.10.011Scopus ID
2-s2.0-43049169911 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
PURPOSE: 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.
METHODS AND MATERIALS: 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.
RESULTS: 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.
CONCLUSION: 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.
Author List
Chen Y, Pandya KJ, Feins R, Johnstone DW, Watson T, Smudzin T, Keng PCAuthor
David Johnstone MD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedAged, 80 and over
Antineoplastic Agents, Phytogenic
Carcinoma, Non-Small-Cell Lung
Female
Humans
Lung Neoplasms
Male
Middle Aged
Paclitaxel
Radiation-Sensitizing Agents
