A Phase II study of paclitaxel-ifosfamide-cisplatin combination in advanced nonsmall cell lung carcinoma

BACKGROUND. The necessity to develop more effective chemotherapy regimens i n advanced nonsmall cell lung carcinoma (NSCLC) prompted the authors to eva luate the paclitaxel-ifosfamide-cisplatin (PIC) combination, developed on t he basis of high individual single-agent activity, in vitro synergism, and tolerance as determined in a previous Phase I study by the authors. PATIENTS. Eligibility criteria included advanced NSCLC (American Joint Comm ittee on Cancer [AJCC]/International Union Against Cancer [UICC] Stage III/ IV), Eastern Cooperative Oncology Group performance status (PS) less than o r equal to 2, no prior chemotherapy, and unimpaired hematopoietic and organ function. Chemotherapy included, paclitaxel 175 (in the first 10 patients) or 200 mg/m(2) on Day 1, ifosfamide: 5 g/m(2) divided over Days 1 and 2, a nd cisplatin 100 mg/m2 divided over Days 1 and 2, recycled every 21 days. G ranulocyte-colony stimulating factor was administered from Day 4 to 13 or u ntil leukocyte count reached greater than or equal to 10,000/mu L. RESULTS, Fifty patients were entered, and all were evaluable for response a nd toxicity: median age, 58 years (range, 40-72), PS, 1 (range, 0-2), Gende r: 44 males and 6 females, Stages ILIA, 6 patients; IIIB, 17; IV, 27; histo logies: adenocarcinoma, 27 patients; squamous, 17; large cells, 5; unspecif ied, 1. Metastatic sites at diagnosis included lymph nodes, 33 patients; bo ne, 6; liver, 5; brain, 10; lung nodules, 7; adrenals, 6; other, 2. Thirty- two of 50 (64%; confidence interval, 50.7-77.3%) evaluable patients respond ed: 4 complete remissions, 28 partial remissions, 13 stable disease, and 5 progressive disease. The quality-of-life score improved in 37 of 50 (74%) p atients. The median response duration was 7 months (range 2-34+); median ti me-to-progression, 8 months (range, 1-36+), median overall survival, 12 mon ths (range, 2-36+). One-par survival was 53%. Grade 3 and 4 toxicities incl uded neutropenia 38 of 50 patients with 21 developing Grade 4 neutropenia ( less than or equal to 5 days) and 7 of these febrile neutropenia (144b); th rombocytopenia, 4 of 50 patients with 1 Grade 4 requiring platelet transfus ions, 1 Grade 3 neuropathy; Grade 1-2 central nervous system toxicity due t o ifosfamide was seen in 22 patients, no renal toxicity, 15 Grade 2 myalgia s, 17 Grade 2 diarrhea, and 10 Grade 3 vomiting. CONCLUSIONS. The PIC combination appears highly active and tolerable in adv anced NSCLC administered in the outpatient setting, Future randomized compa risons to other current standard regimens in NSCLC will be warranted. (C) 2 000 American Cancer Society.