Radiochemotherapy with Taxol for locally advanced non-small cell lung cancer

Background: In the last few years platin-based radiochemotherapy has become standard treatment for patients with advanced, surgically unresectable non-small-cell lung cancer (NSCLC). More recently new chemotherapeutic agents have shown superior activity. Among them paclitaxel (Taxol) is one of the most extensively investigated. Radiotherapy: Despite of promising initial results, locally uncontrolled tumor and distant metastases continue to be the most serious problem of this disease. Improvement of local control can be achieved by escalating radiation dose, by shortening of treatment time with accelerated fractionation or by additional use of radiosensitizing agents. Concerning local control a tumor column-dose relationship has been described. Three-dimensional conformal treatment planning eventually with intensity modulated fields, combined with biological TCP/NTCP calculation models allows risk-adapted escalation and intensification of irradiation. Taxol: A radiosensitizing effect of Taxol by means of G2/M block has been reported. However, radiobiological data are contradictory and suggest a radiosensitizing effect even without cell-cycle arrest. More simultaneous paclitaxel and 60 Gy normally fractionated radiotherapy several prospective dose escalation studies have confirmed a maximum weekly Taxol dose of 60 mg/m2. Changes in paclitaxel application (e.g. daily, twice weekly or biweekly) or in radiotherapy fractionation require a corresponding adaption of Taxol dose. Dose limiting toxicity of this simultaneous treatment is oesophagitis. With respect to the high rate of distant metastases sequential application of combined chemotherapeutic regimens (e.g. Taxol 200 mg/m2/Carboplat AUC 6) is generally recommended. (orig.)