Pharmacodynamics of non-break weekly paclitaxel (Taxol) and pharmacokinetics of Cremophor-EL vehicle: results of a dose-escalation study (Journal article)

Briasoulis, E./ Karavasilis, V./ Tzamakou, E./ Haidou, C./ Piperidou, C./ Pavlidis, N.

We characterized the toxicity and determined the maximum tolerated dose of non-break weekly paclitaxel (Taxol) in chemotherapy-naive cancer patients, and studied pharmacokinetics of the formulation vehicle Cremophor-EL with this schedule. Twenty-three patients with primary refractory solid tumors received weekly paclitaxel at the dose range of 70-200 mg/m2. As dose-limiting toxicity we defined granulocytopenia grade > or =2 causing a treatment delay for more than 2 weeks, or febrile neutropenia or grade >2 organ-specific toxicity. Plasma kinetics of Cremophor-EL were analyzed over the first five courses of treatment. Non-break weekly paclitaxel was feasible at doses up to 110 mg/m2, while granulocytopenia precluded scheduled administration of doses > or =130 mg/m2. Clinically relevant peripheral neurotoxicity tended to occur at around 1500 mg/m2 cumulative dosage at weekly doses > or =110 mg/m2. Detectable Cremophor-EL levels were found in all pre-dose samples, but there was no evidence of accumulation up to the sixth course. Our results, discussed in the light of an overview of published data, suggest that chronic weekly administration of paclitaxel is feasible and with a lack of significant accumulation of Cremophor-EL levels at doses up to 90 mg/m2.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Adult,Aged,Antineoplastic Agents, Phytogenic/*administration & dosage/adverse effects,Area Under Curve,Dose-Response Relationship, Drug,Female,Glycerol/*analogs & derivatives/*pharmacokinetics,Humans,Male,Maximum Tolerated Dose,Middle Aged,Neoplasms/*drug therapy/metabolism/pathology,Neutropenia/chemically induced,Paclitaxel/*administration & dosage/adverse effects,Pharmaceutical Vehicles,Surface-Active Agents/*pharmacokinetics
ISSN: 0959-4973
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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