Phase I, pharmacokinetic, and biological study of erlotinib in combination with paclitaxel and carboplatin in patients with advanced solid tumors

Amita Patnaik, Debra Wood, Anthony W. Tolcher, Marta Hamilton, Jeffrey I. Kreisberg, Lisa A. Hammond, Garry Schwartz, Muralidhar Beeram, Manuel Hidalgo, Monica M. Mita, Julie Wolf, Paul Nadler, Eric K. Rowinsky

Research output: Contribution to journalArticle

Abstract

Purpose: To assess the feasibility of administering erlotinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, in combination with paclitaxel and carboplatin, and to identify pharmacokinetic interactions, evaluate downstream effects of EGFR inhibition on surrogate tissues, and seek preliminary evidence for clinical activity. Experimental Design: Patients with advanced solid malignancies were treated continuously with erlotinib at doses of 100,125, and 150 mg/d orally along with fixed i.v. doses of paclitaxel 225 mg/m2 and carboplatin AUC 6 mg-min/mL, both on day 1 every 3 weeks. Results: Twenty evaluable patients were treated with 136 courses of erlotinib, paclitaxel, and carboplatin. Myelosuppression, skin rash, and diarrhea were the principal toxicities. Dose limiting diarrhea occurred in 1 of 6 patients at the 100 mg erlotinib dose level, whereas 0 of 9 evaluable patients at the 125 mg erlotinib dose level experienced dose limiting toxicity and 3 of 5 evaluable patients at 150 mg erlotinib experienced dose limiting skin rash and neutropenic sepsis. There was no evidence of pharmacokinetic interactions between paclitaxel and erlotinib; however, total carboplatin exposure trended higher in the presence of erlotinib. No consistent downstream effects on EGFR inhibition were found in skin. Durable objective responses were observed in non - small-cell lung and head and neck cancers. Conclusions: A dose level of erlotinib 125 mg combined with paclitaxel 225 mg/m2 and carboplatin AUC 6 mg-min/mL is recommended for disease-directed studies. This phase I trial was followed by a randomized phase III study in non-small-cell lung cancer using a similar regimen.

Original languageEnglish (US)
Pages (from-to)7406-7413
Number of pages8
JournalClinical Cancer Research
Volume12
Issue number24
DOIs
StatePublished - Dec 15 2006
Externally publishedYes

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Carboplatin
Paclitaxel
Pharmacokinetics
Neoplasms
Epidermal Growth Factor Receptor
Exanthema
Non-Small Cell Lung Carcinoma
Area Under Curve
Diarrhea
Erlotinib Hydrochloride
Head and Neck Neoplasms
Protein-Tyrosine Kinases
Sepsis
Research Design
Skin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase I, pharmacokinetic, and biological study of erlotinib in combination with paclitaxel and carboplatin in patients with advanced solid tumors. / Patnaik, Amita; Wood, Debra; Tolcher, Anthony W.; Hamilton, Marta; Kreisberg, Jeffrey I.; Hammond, Lisa A.; Schwartz, Garry; Beeram, Muralidhar; Hidalgo, Manuel; Mita, Monica M.; Wolf, Julie; Nadler, Paul; Rowinsky, Eric K.

In: Clinical Cancer Research, Vol. 12, No. 24, 15.12.2006, p. 7406-7413.

Research output: Contribution to journalArticle

Patnaik, A, Wood, D, Tolcher, AW, Hamilton, M, Kreisberg, JI, Hammond, LA, Schwartz, G, Beeram, M, Hidalgo, M, Mita, MM, Wolf, J, Nadler, P & Rowinsky, EK 2006, 'Phase I, pharmacokinetic, and biological study of erlotinib in combination with paclitaxel and carboplatin in patients with advanced solid tumors', Clinical Cancer Research, vol. 12, no. 24, pp. 7406-7413. https://doi.org/10.1158/1078-0432.CCR-06-1886
Patnaik, Amita ; Wood, Debra ; Tolcher, Anthony W. ; Hamilton, Marta ; Kreisberg, Jeffrey I. ; Hammond, Lisa A. ; Schwartz, Garry ; Beeram, Muralidhar ; Hidalgo, Manuel ; Mita, Monica M. ; Wolf, Julie ; Nadler, Paul ; Rowinsky, Eric K. / Phase I, pharmacokinetic, and biological study of erlotinib in combination with paclitaxel and carboplatin in patients with advanced solid tumors. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 24. pp. 7406-7413.
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T1 - Phase I, pharmacokinetic, and biological study of erlotinib in combination with paclitaxel and carboplatin in patients with advanced solid tumors

AU - Patnaik, Amita

AU - Wood, Debra

AU - Tolcher, Anthony W.

AU - Hamilton, Marta

AU - Kreisberg, Jeffrey I.

AU - Hammond, Lisa A.

AU - Schwartz, Garry

AU - Beeram, Muralidhar

AU - Hidalgo, Manuel

AU - Mita, Monica M.

AU - Wolf, Julie

AU - Nadler, Paul

AU - Rowinsky, Eric K.

PY - 2006/12/15

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N2 - Purpose: To assess the feasibility of administering erlotinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, in combination with paclitaxel and carboplatin, and to identify pharmacokinetic interactions, evaluate downstream effects of EGFR inhibition on surrogate tissues, and seek preliminary evidence for clinical activity. Experimental Design: Patients with advanced solid malignancies were treated continuously with erlotinib at doses of 100,125, and 150 mg/d orally along with fixed i.v. doses of paclitaxel 225 mg/m2 and carboplatin AUC 6 mg-min/mL, both on day 1 every 3 weeks. Results: Twenty evaluable patients were treated with 136 courses of erlotinib, paclitaxel, and carboplatin. Myelosuppression, skin rash, and diarrhea were the principal toxicities. Dose limiting diarrhea occurred in 1 of 6 patients at the 100 mg erlotinib dose level, whereas 0 of 9 evaluable patients at the 125 mg erlotinib dose level experienced dose limiting toxicity and 3 of 5 evaluable patients at 150 mg erlotinib experienced dose limiting skin rash and neutropenic sepsis. There was no evidence of pharmacokinetic interactions between paclitaxel and erlotinib; however, total carboplatin exposure trended higher in the presence of erlotinib. No consistent downstream effects on EGFR inhibition were found in skin. Durable objective responses were observed in non - small-cell lung and head and neck cancers. Conclusions: A dose level of erlotinib 125 mg combined with paclitaxel 225 mg/m2 and carboplatin AUC 6 mg-min/mL is recommended for disease-directed studies. This phase I trial was followed by a randomized phase III study in non-small-cell lung cancer using a similar regimen.

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