Phase I study of vinorelbine and ifosfamide in advanced non-small-cell lung cancer.
OBJECTIVE
We designed a phase I dose-escalation study of vinorelbine on a novel (daily-times-three) schedule with ifosfamide with granulocyte colony-stimulating factor (G-CSF) support to define the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of vinorelbine in this combination.


METHODS
Cohorts of patients with stage IIIB or IV non-small-cell lung cancer (NSCLC) and no prior chemotherapy received vinorelbine starting at 15 mg/m2 on days 1, 2, and 3, and ifosfamide starting at 2.0 g/m2 on days 1, 2, and 3 with G-CSF support for all patients. Cycles were repeated every 21 days. Plasma vinorelbine concentrations were also analyzed.


RESULTS
Forty-two patients were treated. The median age was 58 years (range, 34 to 75) and 41 had a performance status of 0 or 1. The DLT was neutropenia and sepsis at a maximum-administered vinorelbine dose of 35 mg/m2 for 3 days. The recommended phase II dose was vinorelbine 30 mg/m2 with ifosfamide 1.6 g/m2 both given on 3 consecutive days. The overall response rate was 40% (17 of 42; all partial responders). The median survival duration was 50 weeks, with a 1-year survival rate of 48%. Pharmacokinetic analysis showed that vinorelbine in this combination and on this schedule is cleared 1.5 to two times faster than in single-agent once-weekly studies.


CONCLUSIONS
Myelosuppression is the DLT of this regimen with no major subjective toxicities. With tolerable toxicity and an encouraging 1-year survival rate of 48%, further investigation of this new vinorelbine schedule is warranted in this and other combination regimens.
Masters
G A
GA
Department of Medicine, University of Chicago Cancer Research Center, IL 60637-1470, USA.
Hoffman
P C
PC
Hsieh
A
A
Drinkard
L C
LC
Mick
R
R
Samuels
B L
BL
Guaspari
A
A
Golomb
H M
HM
Vokes
E E
EE
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood; D000077235:Vinorelbine
D016179:Granulocyte Colony-Stimulating Factor; D014747:Vinblastine; D000077235:Vinorelbine; D007069:Ifosfamide