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A phase I clinical and pharmacokinetic study of fenretinide combined with paclitaxel and cisplatin for refractory solid tumors.
- Source :
-
Investigational new drugs [Invest New Drugs] 2005 Dec; Vol. 23 (6), pp. 555-62. - Publication Year :
- 2005
-
Abstract
- Background: Fenretinide is a semi-synthetic retinoid that has pro-apoptotic effects as a single agent and synergistically with chemotherapy in vitro. We performed this study to determine the toxicity of cisplatin, paclitaxel and fenretinide in patients with advanced cancer, the recommended phase II dose of these agents together, and the pharmacokinetics (PK) of fenretinide when administered with chemotherapy.<br />Patients and Methods: Fourteen patients (mean age 57.3) were assessable for pharmacokinetics, toxicity and response. Fenretinide was given orally in 2 divided daily doses for 7 days, starting 24 hours prior to cisplatin and paclitaxel. Cisplatin and paclitaxel were given in standard fashion. Cycles were repeated every 3 weeks. Cycle one fenretinide PK was obtained on days 2 and 8.<br />Results: Dose limiting toxicity (Gr 3 diarrhea and Gr 4 neutropenia) was encountered in two patients during cycle one at 80/175/1,800 mg/m(2) of cisplatin/paclitaxel/fenretinide (dose level 2), respectively. Seven patients received 2-8 cycles at the recommended level of 60/135/1,800 (dose level 1). Severe cumulative toxicities included fatigue, nausea/vomiting, neuropathy, and dehydration. Two patients had a partial response and 4 patients had stable disease for up to 8 cycles. PK analysis demonstrated a reduction in fenretinide Cmax on day 8 compared to day 2, accompanying a decrease in AUC.<br />Conclusions: Cisplatin/paclitaxel/fenretinide can be administered safely at 60/135/1,800 mg/m(2) respectively on an every three-week schedule. This combination may have activity in a variety of tumors, however, the number of pills required complicates oral dosing of fenretinide, and limits the applicability of this regimen.
- Subjects :
- Administration, Oral
Adult
Aged
Antineoplastic Agents administration & dosage
Antineoplastic Agents adverse effects
Antineoplastic Agents pharmacokinetics
Antineoplastic Combined Chemotherapy Protocols adverse effects
Antineoplastic Combined Chemotherapy Protocols pharmacokinetics
Cisplatin administration & dosage
Cisplatin adverse effects
Female
Fenretinide administration & dosage
Fenretinide adverse effects
Fenretinide pharmacokinetics
Humans
Male
Middle Aged
Neoplasms metabolism
Paclitaxel administration & dosage
Paclitaxel adverse effects
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0167-6997
- Volume :
- 23
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Investigational new drugs
- Publication Type :
- Academic Journal
- Accession number :
- 16034523
- Full Text :
- https://doi.org/10.1007/s10637-005-1665-2