Concurrent intensive radiotherapy and prolonged continuous-infusion paclitaxel for locally advanced solid tumors: Results of three phase I trials

Locally advanced solid tumors treated with standard current therapy are associated with high rates of tumor persistence and recurrence. Laboratory data suggest the addition of relatively low concentrations (1 to 10 nmol/L) of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), a microtubule-stabilizing drug, to radiotherapy may produce significant radiosensitization, which may be due to cell accumulation at the G₂/M. Direct antitumor activity and radiosensitization appear to correlate more closely with paclitaxel duration of exposure than with peak serum concentration. Therefore, we are conducting three phase I trials designed to test paclitaxel, given by continuous intravenous infusion (24 h/d, 7 d/wk for up to 7 weeks), in combination with standard, curative-intent radiotherapy in patients with locally advanced non-small cell lung cancer, squamous cell carcinoma of the head and neck, and glioblastoma multiforme. Our ultimate goal is to improve local and systemic control and survival for patients with these tumor types. To date, 39 assessable patients are enrolled in this study, and observed toxicities include anemia, lymphopenia, mucositis, and cutaneous toxicities. There has been no dose-limiting toxicity up to 6.5 mg/m²/d, and dose escalation is continuing.