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
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

  • Cancer Research
  • Oncology

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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