Schedule-dependent pulsed paclitaxel radiosensitization for thoracic malignancy

The objective of this study was to apply preclinical research of paclitaxel radiosensitization to the treatment of thoracic malignancy. Human lung can cer cell line NCI520 and epidermoid cell line A431 were investigated in vit ro for radiosensitizing effects of paclitaxel. Optimal schedule of paclitax el treatment was applied to a clinical protocol as well as off-protocol tre atment of thoracic malignancy. Pulsed paclitaxel with concurrent once-daily radiation was delivered every 48 hours during the week using doses of 15 m g/m(2), 20 mg/m(2), or 25 mg/m(2) in a phase I clinical trial of dose escal ation. Preclinical data support the finding that low-dose paclitaxel is suf ficient for radiosensitization. Data also support that delaying radiation i s better than immediate radiation after drug treatment. Twenty-three patien ts have enrolled in the phase I clinical trial. Seventeen patients complete d treatment (6 at 15 mg/m(2); 5 at 20 mg/m(2); and 6 at 25 mg/m(2)). Mean t umor shrinkage at 4 to 6 weeks after therapy was 82%, 84%, and 84% for dose levels I, II, and III, respectively [average primary tumor shrinkage was 8 3% +/- 8% (95% C.I.)]. Locoregional tumor response rate was 100% [12% (2/17 ) complete response and 88% (15/17) partial response] with low rates of tox icity. It is concluded that pulsed low-dose paclitaxel and radiation is a v ery effective and well-tolerated regimen for thoracic malignancy.