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


METHODS
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) </= 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/m(2) 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 >/= 10,000/microL.


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 IIIA, 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-year survival was 53%. Grade 3 and 4 toxicities included neutropenia 38 of 50 patients with 21 developing Grade 4 neutropenia (</= 5 days) and 7 of these febrile neutropenia (14%); 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.
Kosmas
C
C
Medical Oncology Unit, Helena-Venizelou Hospital, Athens, Greece.
Tsavaris
N B
NB
Polyzos
A
A
Kalofonos
H P
HP
Sepsas
E
E
Malamos
N A
NA
Vadiaka
M
M
Dosios
T
T
Antonopoulos
M J
MJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010349:Patient Compliance; D016019:Survival Analysis; D016896:Treatment Outcome
D017239:Paclitaxel; D002945:Cisplatin; D007069:Ifosfamide