BACKGROUND. The necessity to develop more effective chemotherapy
regimens in advanced nonsmall cell lung carcinoma (NSCLC) prompted the
authors to evaluate the paclitaxel-ifosfamide-cisplatin (PIC)
combination, developed on the 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
Committee on Cancer [AJCC]/International Union Against Cancer [UICC]
Stage III/IV), Eastern Cooperative Oncology Group performance status
(PS) less than or 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, and cisplatin 100 mg/m2 divided over Days 1
and 2, recycled every 21 days. Granulocyte-colony stimulating factor was
administered from Day 4 to 13 or until leukocyte count reached greater
than or equal to 10,000/mu L.
RESULTS, Fifty patients were entered, and all were evaluable for
response and toxicity: median age, 58 years (range, 40-72), PS, 1
(range, 0-2), Gender: 44 males and 6 females, Stages ILIA, 6 patients;
IIIB, 17; IV, 27; histologies: adenocarcinoma, 27 patients; squamous,
17; large cells, 5; unspecified, 1. Metastatic sites at diagnosis
included lymph nodes, 33 patients; bone, 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 responded: 4 complete
remissions, 28 partial remissions, 13 stable disease, and 5 progressive
disease. The quality-of-life score improved in 37 of 50 (74%) patients.
The median response duration was 7 months (range 2-34+); median
time-to-progression, 8 months (range, 1-36+), median overall survival,
12 months (range, 2-36+). One-par survival was 53%. Grade 3 and 4
toxicities included 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); thrombocytopenia, 4 of 50 patients with 1
Grade 4 requiring platelet transfusions, 1 Grade 3 neuropathy; Grade 1-2
central nervous system toxicity due to ifosfamide was seen in 22
patients, no renal toxicity, 15 Grade 2 myalgias, 17 Grade 2 diarrhea,
and 10 Grade 3 vomiting.
CONCLUSIONS. The PIC combination appears highly active and tolerable in
advanced NSCLC administered in the outpatient setting, Future randomized
comparisons to other current standard regimens in NSCLC will be
warranted. (C) 2000 American Cancer Society
