Phase I and pharmacokinetic study of irinotecan and docetaxel in patients with advanced solid tumors

Preliminary evidence of clinical activity

Alex Adjei, Cheri E. Klein, Helen Kastrissios, Richard M. Goldberg, Steven Robert Alberts, Henry Clement Pitot, Jeff A Sloan, Joel M Reid, Lorelei J. Hanson, Pamela Atherton, Joseph Rubin, Charles Erlichman

Research output: Contribution to journalArticle

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Abstract

Purpose: The goals of this study were to determine the maximum-tolerated dose and describe the toxicities of the combination of irinotecan and docetaxel administered every 3 weeks to patients with advanced malignancies and, also, to evaluate the effect of irinotecan on the disposition of docetaxel and describe preliminary evidence of antitumor activity. Patients and Methods: Eighteen patients received 85 courses (median, two courses; range, one to 15 courses) of treatment with irinotecan, administered over 90 minutes by intravenous infusion, followed by docetaxel, administered over 60 minutes by intravenous infusion. Four escalating dose levels of irinotecan/docetaxel (160/50 mg/m2, 160/65 mg/m2, 200/65 mg/m2, and 200/75 mg/m2) were studied. Pharmacokinetic analyses were performed to evaluate the effect of irinotecan on the disposition of docetaxel. Results: The most common and dose-limiting toxicity was myelosuppression, which consisted of neutropenia that was severe (National Cancer Institute common toxicity criteria [NCI CTC] grade 4) but brief (< 5 days) in 11 patients, with three episodes of febrile neutropenia. Nonhematologic toxicities of anorexia, nausea, and stomatitis were mild to moderate (NCI CTC grades 1 and 2), but there was one incidence each of both CTC grade 3 anorexia and nausea. All patients had total alopecia. Diarrhea was dose-dependent and severe in four patients who failed to take adequate anti-diarrhea therapy. Five out of 16 assessable patients, one with cholangiocarcinoma, one with leiomyosarcoma, and three with non-small-cell lung cancer, achieved partial remissions. Conclusion: The combination of irinotecan and docetaxel causes significant reversible myelosuppression, which was dose limiting but led to no serious sequelae. There was no evidence of a clinically significant interaction using these two agents in this sequence. The combination showed antitumor activity at all the dose levels tested and should be further studied in a number of tumor types. The recommended phase II dose on this schedule is irinotecan 160 mg/m2 and docetaxel 65 mg/m2. (C) 2000 by American Society of Clinical Oncology.

Original languageEnglish (US)
Pages (from-to)1116-1123
Number of pages8
JournalJournal of Clinical Oncology
Volume18
Issue number5
StatePublished - Mar 2000
Externally publishedYes

Fingerprint

irinotecan
docetaxel
Pharmacokinetics
Neoplasms
National Cancer Institute (U.S.)
Anorexia
Intravenous Infusions
Nausea
Diarrhea
Febrile Neutropenia
Stomatitis
Maximum Tolerated Dose
Cholangiocarcinoma
Leiomyosarcoma
Alopecia
Neutropenia
Non-Small Cell Lung Carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase I and pharmacokinetic study of irinotecan and docetaxel in patients with advanced solid tumors : Preliminary evidence of clinical activity. / Adjei, Alex; Klein, Cheri E.; Kastrissios, Helen; Goldberg, Richard M.; Alberts, Steven Robert; Pitot, Henry Clement; Sloan, Jeff A; Reid, Joel M; Hanson, Lorelei J.; Atherton, Pamela; Rubin, Joseph; Erlichman, Charles.

In: Journal of Clinical Oncology, Vol. 18, No. 5, 03.2000, p. 1116-1123.

Research output: Contribution to journalArticle

Adjei, Alex ; Klein, Cheri E. ; Kastrissios, Helen ; Goldberg, Richard M. ; Alberts, Steven Robert ; Pitot, Henry Clement ; Sloan, Jeff A ; Reid, Joel M ; Hanson, Lorelei J. ; Atherton, Pamela ; Rubin, Joseph ; Erlichman, Charles. / Phase I and pharmacokinetic study of irinotecan and docetaxel in patients with advanced solid tumors : Preliminary evidence of clinical activity. In: Journal of Clinical Oncology. 2000 ; Vol. 18, No. 5. pp. 1116-1123.
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T2 - Preliminary evidence of clinical activity

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AU - Klein, Cheri E.

AU - Kastrissios, Helen

AU - Goldberg, Richard M.

AU - Alberts, Steven Robert

AU - Pitot, Henry Clement

AU - Sloan, Jeff A

AU - Reid, Joel M

AU - Hanson, Lorelei J.

AU - Atherton, Pamela

AU - Rubin, Joseph

AU - Erlichman, Charles

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