Sequential chemo- and radiochemotherapy with weekly paclitaxel (Taxol) 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 dose (MTD) of weekly paclitaxel (PX) in combination with 3D-conformal radiotherapy in non-small cell lung cancer (NSCLC) and the evaluation of side effects, patient outcome and tumor response. Thirty-eight patients with inoperable NSCLC, UICC-stage IIIA (n=14)/IIIB (n=24) received two cycles of induction chemotherapy with PX/carboplatin followed by combined radiochemotherapy (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. Toxicity was determined by WHO criteria. Patients were followed-up 3-monthly. Thirty eight patients have entered the study, 34 patients are evaluable. DLT was esophagitis III degrees, requiring interruption of radiotherapy and was reached at the PX 70 mg/m(2). Two hypersensitivity reactions (50 mg/m(2)) and 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 between 21 and 36% but showed no clear correlation with PX dose. Tumor response (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 the 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/combined approach are promising. A minor increase of pulmonary toxicity of irradiation is suspected.
Willner
J
J
Department of Radiotherapy, University Wuerzburg, Josef-Schneider Strasse 11, 97080 Wuerzburg, Germany. willner@strahlentherapie.uni-wuerzburg.de
Schmidt
M
M
Kirschner
J
J
Lang
S
S
Borgmeier
A
A
Huber
R M
RM
Flentje
M
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015331:Cohort Studies; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004342:Drug Hypersensitivity / Q000209:etiology; D004941:Esophagitis / Q000209:etiology; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D015993:Life Tables; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D020714:Maximum Tolerated Dose; D009325:Nausea / Q000209:etiology; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D011832:Radiation Injuries / Q000209:etiology; D017564:Radiation Pneumonitis / Q000209:etiology; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D012074:Remission Induction; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D014839:Vomiting / Q000209:etiology
D016190:Carboplatin; D017239:Paclitaxel