Docetaxel-ifosfamide combination chemotherapy in patients with metastatic hormone-refractory prostate cancer: a phase I pharmacokinetic study.
This phase I study was designed to evaluate the activity toxicity and pharmacokinetics of docetaxel combined with ifosfamide in the treatment of hormone-refractory prostate cancer. Ten patients received a median of 4.6 treatment cycles. Docetaxel was administered at a dose of 40 mg/m2 in a 1-hour infusion followed by ifosfamide 3,000 mg/m2 in a 24-hour infusion every 3 weeks. The optimal sequence of chemotherapeutic agents was investigated by reversing the order of administration in the second cycle and by collecting a total of six pharmacokinetic blood samples per cycle from all patients during the first and second cycles. The sequence of administration did not influence the pharmacokinetics of docetaxel. Prostate-specific antigen (PSA) responses were observed in four out of nine patients, with a PSA response rate of 44.4% (complete response + partial response). The treatment was well tolerated. No grade IV toxicities were recorded and grade III leucopenia resulted in dose-reductions in 6 cycles (13.3%). The pharmacokinetic parameters of docetaxel were similar in both sequences. Our recommendation for further phase II studies is ifosfamide followed by low-dose docetaxel. Further phase II efficacy studies are warranted.
Hervonen
P
P
Department of Oncology, Tampere University Hospital, Tampere, Finland. petteri.hervonen@pshp.fi
Jekunen
A
A
Lefebvre
P
P
Kellokumpu-Lehtinen
P
P
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D000077143:Docetaxel; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
D043823:Taxoids; D000077143:Docetaxel; D007069:Ifosfamide