Phase I and pharmacokinetic study of weekly docetaxel, cisplatin, and daily capecitabine in patients with advanced solid tumors

Marwan G. Fakih, Patrick J. Creaven, Nithya Ramnath, Donald Trump, Milind Javle, Sandra Strychor, Trisha V.W. Repinski, Beth A. Zamboni, James K Schwarz, Renee A. French, William C. Zamboni

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: Docetaxel, cisplatin, and capecitabine are three active chemotherapeutic agents with different mechanisms of action. This phase I study investigated the feasibility and pharmacokinetics of this combination given on a weekly schedule. Experimental Design: Docetaxel and cisplatin were given i.v. over 30 minutes on days 1 and 8 and capecitabine was given orally bid on days 1 to 14 (every 21 days). Escalation occurred in cohorts of three patients until the maximum tolerated dose was defined. Pharmacokinetics studies of docetaxel and total and ultrafiltrate platinum after cisplatin administration were done on cycle 1 (with capecitabine) and cycle 2 (without capecitabine). Results: Twenty-five patients were enrolled. Two of six patients at dose level 5 had a dose-limiting infection and diarrhea. One of six evaluable patients at dose level 4 (27 mg/m2 docetaxel, 27 mg/m2 cisplatin, 825 mg/m2 capecitabine) had a dose-limiting hypomagnesemia. Pharmacokinetics of docetaxel were similar on cycles 1 and 2. Area under the plasma concentrations versus time curves of total platinum was significantly greater in cycle 2 compared with cycle 1 (P = 0.001). There was no difference in the disposition of docetaxel on cycles 1 and 2. Conclusions: The recommended docetaxel, cisplatin, and capecitabine dose for phase II studies is 27/27/825 mg/m2. The alteration in total and ultrafiltrate platinum disposition on cycle 2 compared with cycle 1 may be inherent to sequential cisplatin administration; however, prior treatment with capecitabine cannot be ruled out as a factor.

Original languageEnglish (US)
Pages (from-to)5942-5949
Number of pages8
JournalClinical Cancer Research
Volume11
Issue number16
DOIs
StatePublished - Aug 15 2005

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docetaxel
Cisplatin
Pharmacokinetics
Platinum
Neoplasms
Maximum Tolerated Dose
Feasibility Studies
Capecitabine
Diarrhea
Appointments and Schedules
Research Design

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Phase I and pharmacokinetic study of weekly docetaxel, cisplatin, and daily capecitabine in patients with advanced solid tumors. / Fakih, Marwan G.; Creaven, Patrick J.; Ramnath, Nithya; Trump, Donald; Javle, Milind; Strychor, Sandra; Repinski, Trisha V.W.; Zamboni, Beth A.; Schwarz, James K; French, Renee A.; Zamboni, William C.

In: Clinical Cancer Research, Vol. 11, No. 16, 15.08.2005, p. 5942-5949.

Research output: Contribution to journalArticle

Fakih, MG, Creaven, PJ, Ramnath, N, Trump, D, Javle, M, Strychor, S, Repinski, TVW, Zamboni, BA, Schwarz, JK, French, RA & Zamboni, WC 2005, 'Phase I and pharmacokinetic study of weekly docetaxel, cisplatin, and daily capecitabine in patients with advanced solid tumors', Clinical Cancer Research, vol. 11, no. 16, pp. 5942-5949. https://doi.org/10.1158/1078-0432.CCR-05-0116
Fakih, Marwan G. ; Creaven, Patrick J. ; Ramnath, Nithya ; Trump, Donald ; Javle, Milind ; Strychor, Sandra ; Repinski, Trisha V.W. ; Zamboni, Beth A. ; Schwarz, James K ; French, Renee A. ; Zamboni, William C. / Phase I and pharmacokinetic study of weekly docetaxel, cisplatin, and daily capecitabine in patients with advanced solid tumors. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 16. pp. 5942-5949.
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AU - Fakih, Marwan G.

AU - Creaven, Patrick J.

AU - Ramnath, Nithya

AU - Trump, Donald

AU - Javle, Milind

AU - Strychor, Sandra

AU - Repinski, Trisha V.W.

AU - Zamboni, Beth A.

AU - Schwarz, James K

AU - French, Renee A.

AU - Zamboni, William C.

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Y1 - 2005/8/15

N2 - Purpose: Docetaxel, cisplatin, and capecitabine are three active chemotherapeutic agents with different mechanisms of action. This phase I study investigated the feasibility and pharmacokinetics of this combination given on a weekly schedule. Experimental Design: Docetaxel and cisplatin were given i.v. over 30 minutes on days 1 and 8 and capecitabine was given orally bid on days 1 to 14 (every 21 days). Escalation occurred in cohorts of three patients until the maximum tolerated dose was defined. Pharmacokinetics studies of docetaxel and total and ultrafiltrate platinum after cisplatin administration were done on cycle 1 (with capecitabine) and cycle 2 (without capecitabine). Results: Twenty-five patients were enrolled. Two of six patients at dose level 5 had a dose-limiting infection and diarrhea. One of six evaluable patients at dose level 4 (27 mg/m2 docetaxel, 27 mg/m2 cisplatin, 825 mg/m2 capecitabine) had a dose-limiting hypomagnesemia. Pharmacokinetics of docetaxel were similar on cycles 1 and 2. Area under the plasma concentrations versus time curves of total platinum was significantly greater in cycle 2 compared with cycle 1 (P = 0.001). There was no difference in the disposition of docetaxel on cycles 1 and 2. Conclusions: The recommended docetaxel, cisplatin, and capecitabine dose for phase II studies is 27/27/825 mg/m2. The alteration in total and ultrafiltrate platinum disposition on cycle 2 compared with cycle 1 may be inherent to sequential cisplatin administration; however, prior treatment with capecitabine cannot be ruled out as a factor.

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