[High-dose ifosfamide in patients with stage IV non-small cell lung cancer: phase II trial from the Groupe français de pneumo-cancérologie (GFPC)].
OBJECTIVE
To assess the toxicity and efficacy of high dose ifosfamide in stage IV NSCLC.


METHODS
In a previous trial, we have determined maximum tolerated dose for 3-days ifosfamide treatment by 3-weeks schedule as 9 g/m2 according to hematologic tolerance. We therefore set up a phase II to study the toxicity and efficacy of this schedule in chemotherapy naive metastatic NSCLC. Ifosfamide (+ mesna 1 g/m2) was administered by a two hour infusion (3 g/m2) for three days every three weeks. Patients received three mesna bolus infusions (1 g/m2) at 4, 8 and 12 hours after the end of ifosfamide infusion. Antitumoral efficacy was performed after 2 cycles and treatment could be pursued for responding patients until disease progression. From september 1995 to January 1997, 31 patients have been included in this study. Median age was 60.7 years +/- 1.33 (41-70) for 27 males and 4 females. Patients (pts) presented metastases in lung for 10 pts, bone for 10 pts, liver for 6 pts, adrenal for 4 pts and multiorgan metastatic localisation for 1 patient. Seven patients were unassessable: 1 lost for follow-up, 1 sudden death, 5 treatment interruptions before evaluation time and 3 toxic deaths (9.6%).


RESULTS
neutropenia grade 4 (10 pts and 1 death), cardiotoxicity grade 4 (1 pt) and 2 deaths following neurotoxicity grade 4. We achieve 4 partial responses (13%, 95CI: 3.6-29.8), 10 progressive diseases (32.3%, 95CI: 16.7-51.4) and 10 stabilizations (32.3%, 95CI: 16.7-51.4). Median response duration was 91 days +/- 55 d. Median survival was 9.3 months, e.g. 280 days (8-863). Overall survival at one year is 48%.


CONCLUSIONS
This modality of high dose ifosfamide is as effective as standard monotherapy schedules in stage IV NSCLC. Unexpected toxicities particularly hematological ones could be due to a short duration of fractionated treatment. Results in term of survival leads us to further evaluate ifosfamide monotherapy treatment on a 5-day schedule basis.
Vergnenègre
A
A
Service de l information médicale et de l'évaluation, Hôpital universitaire du Cluzeau, Limoges.
Thomas
P
P
Robinet
G
G
Pibarot
M
M
Paillotin
D
D
Vernejoux
J M
JM
Thiberville
L
L
Lena
H
H
Kleisbauer
J P
JP
Gimonet
J F
JF
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D015080:Mesna / Q000627:therapeutic use; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D015080:Mesna; D007069:Ifosfamide