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/m2) as a 3-h IV infusion followed by DTX (50 mg/m2) 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/m2) and PTX (135 mg/m2) 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/m2) followed by PTX (135 mg/m2) 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.
Keywords
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Article info
Publication history
Accepted:
October 19,
2005
Received in revised form:
October 18,
2005
Received:
September 15,
2005
Identification
Copyright
© 2006 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
