Sequential chemo- and radiochemotherapy with weekly paclitaxel (Taxol (R))and 3D-conformal radiotherapy of stage III inoperable non small cell lung cancer - Results of a dose escalation study

The purpose of this study was the determination of the maximum tolerable do se (MTD) of weekly paclitaxel (PX) in combination with 3D-conformal radioth erapy in non-small cell lung cancer (NSCLC) and the evaluation of side effe cts, patient outcome and tumor response. Thirty-eight patients with inopera ble NSCLC, UICC-stage IIIA (n = 14)/IIIB (n = 24) received two cycles of in duction chemotherapy with PX/carboplatin followed by combined radiochemothe rapy (60 Gy/6 weeks) with weekly PX which was escalated in cohorts of four patients until dose limiting toxicity (DLT) was reached. Starting level was 40 mg/m(2). 3D-conformal radiotherapy was applied in all patients. Toxicit y was determined by WHO criteria. Patients were followed-up 3-monthly. Thir ty eight patients have entered the study, 34 patients are evaluable. DLT wa s esophagitis III degrees, requiring interruption of radiotherapy and was r eached at the PX 70 mg/m(2). Two hypersensitivity reactions (50 mg/m(2)) an d one leucopenia III degrees (60 mg/m(2)) were observed. Only one patient ( 60 mg/m(2), 50 Gy) completely aborted treatment. The pneumonitis rate was b etween 21 and 36% but showed no clear correlation with PX dose. Tumor respo nse (PR and CR) defined by CT-scan 6 weeks following radiotherapy was 88% ( 30/34). The 1- and 2-year survival rate is 73% and 34%. We conclude that th e MTD of weekly PX with 60 Gy normofractionated radiotherapy is 60 mg/m(2). The DLT is esophagitis. Response and survival data of this sequential/comb ined approach are promising. A minor increase of pulmonary toxicity of irra diation is suspected. (C) 2001 Elsevier Science Ireland Ltd. All rights res erved.