A phase I and pharmacokinetic trial of erlotinib in combination with weekly docetaxel in patients with taxane-naive malignancies

E. Gabriela Chiorean, Jennifer M. Porter, Anne E. Foster, Amal S.H. Al Omari, Christy A. Yoder, Karen L. Fife, R. Matthew Strother, Daryl J. Murry, Menggang Yu, David R. Jones, Christopher J. Sweeney

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Abstract

Purpose: This study aimed to define the maximum tolerated dose of weekly docetaxel combined with daily erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor. Experimental Design: Patients with any solid tumor received 150 mg erlotinib with escalating doses of docetaxel (20, 25, 30, and 35mg/m2) on days 1, 8, and 15 every 28 days. The pharmacokinetics of docetaxel and erlotinib was determined on cycle 2, day 1. Erlotinib was given for a maximum of 12 cycles and docetaxel was given for up to 6 cycles. Results: Twenty-five patients (17 males and 8 females) were enrolled with a median age of 56 years (range, 34-76); Eastern Cooperative Oncology Group performance status of 0/1 was 20/5. One patient had a dose-limiting toxicity in cycle 1 at the 25 mg/m2 level (grade 3 enterocolitis). At 35 mg/m2 docetaxel dose level, 6 of 10 patients required dose reductions to 30 mg/m2 beyond cycle 1 due to neutropenia (3 patients) and mucositis, increased bilirubin, and diarrhea (1 patient each). The clearance of docetaxel and erlotinib of 61.7 and 8.16 L/h, respectively, did not seem to differ from historical controls. Responses were seen in non-small cell lung cancer, prostate cancer, and hepatobiliary cancers, including a complete response lasting 36+ months in a patient with hepatocellular carcinoma. Conclusion: Although no maximum tolerated dose was reached in cycle 1with 35 mg/m2 docetaxel, repetitive dosing proved intolerable in a substantial number of patients; thus, the recommended phase II dose of weekly docetaxel is 30 mg/m2 when combined with 150 mg of daily erlotinib.

Original languageEnglish (US)
Pages (from-to)1131-1137
Number of pages7
JournalClinical Cancer Research
Volume14
Issue number4
DOIs
StatePublished - Feb 15 2008

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docetaxel
Pharmacokinetics
Neoplasms
Maximum Tolerated Dose
Prostatic Neoplasms
Enterocolitis
Mucositis
Erlotinib Hydrochloride
taxane
Neutropenia
Bilirubin
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Chiorean, E. G., Porter, J. M., Foster, A. E., Al Omari, A. S. H., Yoder, C. A., Fife, K. L., ... Sweeney, C. J. (2008). A phase I and pharmacokinetic trial of erlotinib in combination with weekly docetaxel in patients with taxane-naive malignancies. Clinical Cancer Research, 14(4), 1131-1137. https://doi.org/10.1158/1078-0432.CCR-07-0437

A phase I and pharmacokinetic trial of erlotinib in combination with weekly docetaxel in patients with taxane-naive malignancies. / Chiorean, E. Gabriela; Porter, Jennifer M.; Foster, Anne E.; Al Omari, Amal S.H.; Yoder, Christy A.; Fife, Karen L.; Strother, R. Matthew; Murry, Daryl J.; Yu, Menggang; Jones, David R.; Sweeney, Christopher J.

In: Clinical Cancer Research, Vol. 14, No. 4, 15.02.2008, p. 1131-1137.

Research output: Contribution to journalArticle

Chiorean, EG, Porter, JM, Foster, AE, Al Omari, ASH, Yoder, CA, Fife, KL, Strother, RM, Murry, DJ, Yu, M, Jones, DR & Sweeney, CJ 2008, 'A phase I and pharmacokinetic trial of erlotinib in combination with weekly docetaxel in patients with taxane-naive malignancies', Clinical Cancer Research, vol. 14, no. 4, pp. 1131-1137. https://doi.org/10.1158/1078-0432.CCR-07-0437
Chiorean, E. Gabriela ; Porter, Jennifer M. ; Foster, Anne E. ; Al Omari, Amal S.H. ; Yoder, Christy A. ; Fife, Karen L. ; Strother, R. Matthew ; Murry, Daryl J. ; Yu, Menggang ; Jones, David R. ; Sweeney, Christopher J. / A phase I and pharmacokinetic trial of erlotinib in combination with weekly docetaxel in patients with taxane-naive malignancies. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 4. pp. 1131-1137.
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AU - Al Omari, Amal S.H.

AU - Yoder, Christy A.

AU - Fife, Karen L.

AU - Strother, R. Matthew

AU - Murry, Daryl J.

AU - Yu, Menggang

AU - Jones, David R.

AU - Sweeney, Christopher J.

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N2 - Purpose: This study aimed to define the maximum tolerated dose of weekly docetaxel combined with daily erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor. Experimental Design: Patients with any solid tumor received 150 mg erlotinib with escalating doses of docetaxel (20, 25, 30, and 35mg/m2) on days 1, 8, and 15 every 28 days. The pharmacokinetics of docetaxel and erlotinib was determined on cycle 2, day 1. Erlotinib was given for a maximum of 12 cycles and docetaxel was given for up to 6 cycles. Results: Twenty-five patients (17 males and 8 females) were enrolled with a median age of 56 years (range, 34-76); Eastern Cooperative Oncology Group performance status of 0/1 was 20/5. One patient had a dose-limiting toxicity in cycle 1 at the 25 mg/m2 level (grade 3 enterocolitis). At 35 mg/m2 docetaxel dose level, 6 of 10 patients required dose reductions to 30 mg/m2 beyond cycle 1 due to neutropenia (3 patients) and mucositis, increased bilirubin, and diarrhea (1 patient each). The clearance of docetaxel and erlotinib of 61.7 and 8.16 L/h, respectively, did not seem to differ from historical controls. Responses were seen in non-small cell lung cancer, prostate cancer, and hepatobiliary cancers, including a complete response lasting 36+ months in a patient with hepatocellular carcinoma. Conclusion: Although no maximum tolerated dose was reached in cycle 1with 35 mg/m2 docetaxel, repetitive dosing proved intolerable in a substantial number of patients; thus, the recommended phase II dose of weekly docetaxel is 30 mg/m2 when combined with 150 mg of daily erlotinib.

AB - Purpose: This study aimed to define the maximum tolerated dose of weekly docetaxel combined with daily erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor. Experimental Design: Patients with any solid tumor received 150 mg erlotinib with escalating doses of docetaxel (20, 25, 30, and 35mg/m2) on days 1, 8, and 15 every 28 days. The pharmacokinetics of docetaxel and erlotinib was determined on cycle 2, day 1. Erlotinib was given for a maximum of 12 cycles and docetaxel was given for up to 6 cycles. Results: Twenty-five patients (17 males and 8 females) were enrolled with a median age of 56 years (range, 34-76); Eastern Cooperative Oncology Group performance status of 0/1 was 20/5. One patient had a dose-limiting toxicity in cycle 1 at the 25 mg/m2 level (grade 3 enterocolitis). At 35 mg/m2 docetaxel dose level, 6 of 10 patients required dose reductions to 30 mg/m2 beyond cycle 1 due to neutropenia (3 patients) and mucositis, increased bilirubin, and diarrhea (1 patient each). The clearance of docetaxel and erlotinib of 61.7 and 8.16 L/h, respectively, did not seem to differ from historical controls. Responses were seen in non-small cell lung cancer, prostate cancer, and hepatobiliary cancers, including a complete response lasting 36+ months in a patient with hepatocellular carcinoma. Conclusion: Although no maximum tolerated dose was reached in cycle 1with 35 mg/m2 docetaxel, repetitive dosing proved intolerable in a substantial number of patients; thus, the recommended phase II dose of weekly docetaxel is 30 mg/m2 when combined with 150 mg of daily erlotinib.

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