Taxol plus radiation for head and neck cancer

Taxol (paclitaxel) is the prototype of a new class of cancer drugs, the taxanes. This group of anticancer agents have a novel mechanism of action, broad clinical activity, and potential as clinical radiosensitizers. Paclitaxel may be the most efficacious single chemotherapy agent for head and neck cancer with a 40% response rate for patients with recurrent disease. As it is possible to achieve durable control with radiotherapy of locally advanced head and neck cancer in only a minority of cases, chemotherapy drugs such as paclitaxel are being used with radiotherapy in an attempt to improve tumor control. Paclitaxel stabilizes microtubules and leads to accumulation of cells at the G2/mitosis phase of the cell cycle, which is a necessary condition for its antitumor effect, and also the phase with the greatest relative radiosensitivity. Paclitaxel has been shown to be a radiosensitizer in vitro for some but not all cell lines studied. In vitro dose-response data for paclitaxel paradoxically suggest that prolonged exposure to relatively low concentrations--those easily achievable clinically--may be more effective than higher doses both for direct cytotoxicity and radiosensitization. These data suggest that paclitaxel has potential as a clinical radiosensitizer for head and neck cancer, and phase I trials are in progress. We review the laboratory and clinical studies supplying the rationale, risks, and potential benefits for the concurrent use of paclitaxel and radiotherapy, the current investigational clinical trials, including our NCI-sponsored phase I trials with continuous infusion paclitaxel as a potential radiosensitizer for head and neck cancer.(ABSTRACT TRUNCATED AT 250 WORDS)