A phase I clinical and pharmacokinetic study of paclitaxel and docetaxel given in combination in patients with solid tumours.
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.
Izquierdo
Miguel Angel
MA
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.
García
Margarita
M
Pontón
José Luis
JL
Martínez
Marisa
M
Valentí
Vicente
V
Navarro
Matilde
M
Gil
Miguel
M
Cardenal
Felipe
F
Mesía
Ricard
R
Pérez
Xavier
X
Salazar
Ramón
R
Germà-Lluch
Josep Ramón
JR
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
D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel