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Erlotinib plus gemcitabine in patients with unresectable pancreatic cancer and other solid tumors: phase IB trial

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Abstract

Purpose

The purpose of this phase IB trial was to evaluate the tolerability, pharmacokinetics and preliminary evidence of antitumor activity of erlotinib plus gemcitabine in patients with pancreatic cancer and other solid tumors.

Patients and methods

Patients included those with advanced pancreatic adenocarcinoma or other malignancies potentially responsive to gemcitabine. In the escalating phase of the trial, patients were enrolled in sequential cohorts using 100 or 150 mg oral daily dosing of erlotinib. Gemcitabine dose was 1,000 mg/m2 weekly ×7 (first cycle), then weekly ×3, every 4 weeks.

Results

Twenty-six patients completed at least one course on study. In Cohort IA, at the 100 mg/day dose of erlotinib, three patients have developed grade 3 transaminase elevations. After stricter inclusion criteria were adopted (Cohort IB), no additional events of grade 3 transaminase elevations were observed and the dose of erlotinib was escalated to 150 mg/day (Cohorts IB and IIB) without reaching dose-limiting toxicities. The most common toxicities included diarrhea, skin rash, fatigue and neutropenia. The pharmacokinetic analyses did not reveal any significant interactions between erlotinib and gemcitabine. Objective responses were seen in two patients: cholangiocarcinoma and pancreatic cancer. Patients with unresectable or metastatic pancreatic cancer (n = 15) had a median progression-free survival of 289 days, the estimated overall survival of 389 days (12.5 months), and a 1-year survival rate of 51%.

Conclusion

The 150 mg/day dose of erlotinib can be safely administered in combination with standard dose gemcitabine in selected patients with pancreatic cancer and other advanced solid tumors. Promising antitumor activity has been observed in patients with pancreatic cancer.

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Acknowledgment

Supported by OSI Pharmaceuticals Inc., Melville, NY, USA.

Author information

Authors and Affiliations

  1. Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ, 85724, USA

    Tomislav Dragovich & Daniel D. Von Hoff

  2. Beth Israel Deaconess Medical Center, Boston, MA, USA

    Mark Huberman

  3. Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX, USA

    Eric K. Rowinsky & Amita Patnaik

  4. OSI Pharmaceuticals Inc., Boulder, CO, USA

    Paul Nadler, Debra Wood, Marta Hamilton, George Hage & Julie Wolf

Authors
  1. Tomislav Dragovich
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  2. Mark Huberman
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  3. Daniel D. Von Hoff
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  4. Eric K. Rowinsky
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  5. Paul Nadler
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  6. Debra Wood
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  7. Marta Hamilton
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  8. George Hage
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  9. Julie Wolf
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  10. Amita Patnaik
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Corresponding author

Correspondence to Tomislav Dragovich.

Additional information

Data were previously presented at the 40th annual meeting of the American Society of Clinical Oncology, New Orleans, LA, USA, May 12–15, 2004.

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Dragovich, T., Huberman, M., Von Hoff, D.D. et al. Erlotinib plus gemcitabine in patients with unresectable pancreatic cancer and other solid tumors: phase IB trial. Cancer Chemother Pharmacol 60, 295–303 (2007). https://doi.org/10.1007/s00280-006-0389-0

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  • DOI: https://doi.org/10.1007/s00280-006-0389-0

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