title: A phase I clinical and pharmacokinetic study of paclitaxel and docetaxel given in combination in patients with solid tumours.
abstract: The aim of this study was to determine the safety and feasibility profile of paclitaxel (PTX) and docetaxel (DTX) in combination and the pharmacokinetic and pharmacodynamic interaction between these two drugs in two different alternated sequences of administration. The starting dose was PTX (100 mg/m(2)) as a 3-h IV infusion followed by DTX (50 mg/m(2)) as 1-h IV infusion or the alternative sequence in every other patient. The sequence was alternated in the second course in each patient treated. Cycle duration was 21 days. Twenty patients received 103 cycles of treatment through three dose levels. Febrile neutropenia and grade 4 neutropenia lasting longer than 7 days were dose-limiting and defined the toxic dose of DTX (50 mg/m(2)) and PTX (135 mg/m(2)) in patients with prior treatment and the recommended dose in patients without prior treatment. Non-hematological toxicities included asthenia, neuropathy, arthralgia/myalgia and stomatitis. Pharmacokinetics of DTX were significantly affected by the sequence. Nadir ANC was more profound when DTX was administered first (P=0.022). There were one complete response and six partial responses, giving an overall response rate of 35%. DTX (50 mg/m(2)) followed by PTX (135 mg/m(2)) can be administered safely and it is an active regimen. The pharmacokinetics of PTX are not influenced by DTX but DTX pharmacokinetics depend on the sequence of administration, which influences its haematological toxicity profile.
authors.affiliation: Department of Clinical Oncology, IDIBELL, Institut Català d'Oncologia, Hospital Durán i Reynals, Avda. Gran Vía, s/n, Km 2,7, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Izquierdo
authors.forename: Margarita
authors.initials: M
authors.lastname: García
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pontón
authors.forename: Marisa
authors.initials: M
authors.lastname: Martínez
authors.forename: Vicente
authors.initials: V
authors.lastname: Valentí
authors.forename: Matilde
authors.initials: M
authors.lastname: Navarro
authors.forename: Miguel
authors.initials: M
authors.lastname: Gil
authors.forename: Felipe
authors.initials: F
authors.lastname: Cardenal
authors.forename: Ricard
authors.initials: R
authors.lastname: Mesía
authors.forename: Xavier
authors.initials: X
authors.lastname: Pérez
authors.forename: Ramón
authors.initials: R
authors.lastname: Salazar
authors.forename: Josep Ramón
authors.initials: JR
authors.lastname: Germà-Lluch
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077143:Docetaxel; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel