PHASE I-II TRIAL OF CONCOMITANT CONTINUOUS CARBOPLATIN (CBDCA) INFUSION AND RADIOTHERAPY IN ADVANCED NONSMALL CELL LUNG-CANCER WITH EVALUATION FOR SURGERY - FINAL REPORT

Purpose: The goal of this trial was to determine the maximum tolerable dose when carboplatin (CBDCA) was administered in continuous infusion concurrently With radiotherapy in patients with nonsmall cell lung ca ncer. Methods and Materials: From October 1989 to July 1993, 54 patien ts were studied (male/female ratio: 44 to 10), median age was 62 years , Two patients had Stage II cancer, 22 had Stage IIIA, 24 had Stage II IB, and 6 had Stage IV, Carboplatin was given for 96 h, starting at a dose of 30 mg/m(2)/day: 13 patients received 30 mg/m(2)/day (group A), 12 patients received 50 mg/m(2)/day (group B), 12 patients received 7 0 mg/m(2)/day (group C), 10 patients received 90 mg/m(2)/day (group D) , and 7 patients 110 mg/m(2)/day (group E), The radiation dose was 50. 40 Gy delivered to the target volume in 5.3 weeks. Results: Fifty-thre e of 54 patients were evaluable for toxicity and 52 out of 54 for resp onse. Toxicity (Miller score): Myelotoxicity: in groups A and B it was almost absent; in groups C and D it was moderate (leukopenia G1-2:45. 4 % patients; trombocytopenia G1-2:22.7 %, G3:9 %; anemia G1-2:9 %); o nly in group E was it severe (leukopenia G1 and G3 16.6% respectively; trombocytopenia G3:33.3%, G4:16.6%; anemia G1-2:50%), Nephrotoxicity was present only in one patient of group E and was Grade 3, Nausea and vomiting were related to CBDCA dose. One patient in Group E died of i ntractable toxicity 3 days after the end of infusion; then the study w as closed, The limiting toxicity dose was shown to be 110 mg/m(2)/day given for 96 h, Clinical response rate: Twenty-six of 52 patients had major response, 24 had minor response, and only 2 patients had progres sion of disease, Surgery: Twenty-one of 52 tumors were judged resectab le: 18 patients had complete tumor resection, 1 had exploratory thorac otomy, and 2 patients refused surgery, Pathological response rate: Fiv e patients had pathologic state TO or Tis. Conclusions: These results indicate that the maximum tolerable dose of CBDCA infusion for 96 h is 90 mg/m(2)/day and this schedule seems to produce an appreciable resp onse rate, Therefore, we have started a Phase II trial, which will per mit us to define the true efficacy of this schedule. Copyright (C) 199 7 Elsevier Science Inc.