V. Lorusso et al., COMBINED CARBOPLATIN PLUS IFOSFAMIDE AND CISPLATIN IN PATIENTS WITH ADVANCED OVARIAN-CARCINOMA - A PHASE I-II STUDY, Gynecologic oncology, 68(2), 1998, pp. 172-177
Because of the relative lack of overlapping toxicity, carboplatin (PPL
) and cisplatin (CDDP) can be easily combined for treatment of ovarian
cancer to increase total platinum dose intensity. Ifosfamide (IFO), o
ne of the most effective single agents in ovarian cancer, has a low he
matological toxicity when administered in continuous infusion. From Ja
nuary 1991 to December 1993, 34 patients with advanced ovarian cancer,
previously untreated with chemo- or radiotherapy, were enrolled in a
phase I-II study with the aim of determining the maximum tolerated dos
e (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (
300 mg/m(2) on day 1) and IFO (4,000 mg/m(2)/24 h by continuous infusi
on on day 1). The initial dose level of CDDP was 40 mg/m(2), which was
continuously increased by 10 mg/m(2) up to the MTD defined as one dos
e level below that inducing dose-limiting toxicity (DLT) in at least t
wo-thirds of treated patients; no dose escalation was allowed in the s
ame patient. Grade 3-4 leukopenia and thrombocytopenia were observed i
n 54 and 49% of patients, respectively. The DLT was reached at 70 mg/m
(2) and therefore the dose recommended for the phase II study was 60 m
g/m(2). Complete (CR) plus partial response was observed in 88% of pat
ients with a 21% pathological CR. With a minimum follow-up of 32 month
s (median 40 months), median progression-free survival and overall sur
vival were 21 and 39 months, respectively. In conclusion, the combinat
ion of CDDP, PPL, and IFO provides an effective regimen for ovarian ca
ncer with an acceptable toxicity profile. (C) 1998 Academic Press.