A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer.
OBJECTIVE
We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen.


METHODS
We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed.


RESULTS
Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia.


CONCLUSIONS
This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.
Masters
G A
GA
Department of Medicine, University of Chicago, IL, USA. g-masters@nwu.edu
Mauer
A M
AM
Hoffman
P C
PC
Wyka
D
D
Samuels
B L
BL
Krauss
S A
SA
Watson
S
S
Golomb
H
H
Vokes
E E
EE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D005260:Female; D000069585:Filgrastim; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011994:Recombinant Proteins; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D014747:Vinblastine; D017239:Paclitaxel; D000069585:Filgrastim; D000077235:Vinorelbine; D007069:Ifosfamide