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The Community Oncologist

Paclitaxel/Carboplatin plus Bevacizumab/Erlotinib in the First-Line Treatment of Patients with Carcinoma of Unknown Primary Site

^aSarah Cannon Research Institute, Nashville, Tennessee, USA; ^bTennessee Oncology, PLLC, Nashville, Tennessee, USA; ^cOncology Hematology Care, Inc., Cincinnati, Ohio, USA; ^dIntegrated Community Oncology Network, Jacksonville, Florida, USA

Key Words. Paclitaxel • Carboplatin • Bevacizumab • Erlotinib • Carcinoma of unknown primary • First-line treatment • Empiric chemotherapy

Correspondence: John D. Hainsworth, M.D., Sarah Cannon Research Institute, 3322 West End Avenue, Suite 900, Nashville, Tennessee 37203, USA. Telephone: 615-329-7274; Fax: 615-340-1535; e-mail: jhainsworth{at}tnonc.com, cc: aso{at}scresearch.net

Received June 12, 2009; accepted for publication November 8, 2009; first published online in THE ONCOLOGIST Express on December 4, 2009.

Disclosures: John D. Hainsworth: Research funding/contracted research: Genentech, paid to Sarah Cannon Research Institute; David R. Spigel: Consultant/advisory role: Genentech; Research funding/contracted research: Genentech, OSI; Dana S. Thompson: None; Patrick B. Murphy: None; Cassie M. Lane: Employment/leadership position: Sarah Cannon Research Institute; Research funding/contracted research: Sarah Cannon Research Institute; David M. Waterhouse: None; Yuval Naot: None; F. Anthony Greco: None.

This article discusses bevacizumab (Genentech, Inc.) and erlotinib (OSI Pharmaceuticals, Inc.) being investigated as combination therapy in the treatment of carcinoma.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

Introduction. This phase II trial evaluated the efficacy and toxicity of the combination of paclitaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with carcinoma of unknown primary site (CUP).

Methods. Patients with previously untreated CUP (adenocarcinoma, poorly differentiated carcinoma, poorly differentiated squamous carcinoma) without clinical or pathologic characteristics of a well-defined treatable subset were eligible. All patients received paclitaxel, carboplatin, bevacizumab, and erlotinib. Treatment cycles were repeated at 21-day intervals. After four cycles, paclitaxel and carboplatin were discontinued; bevacizumab–erlotinib treatment was continued until tumor progression. Patients were initially evaluated for response after completion of two treatment cycles; re-evaluations occurred every 6 weeks thereafter.

Results. Forty-nine of 60 patients (82%) completed four cycles of therapy, and 44 patients (73%) subsequently received maintenance bevacizumab and erlotinib. Thirty-two patients (53%) had major responses to treatment; an additional 18 patients had stable disease. After a median follow-up of 19 months, the median progression-free survival time was 8 months, with 38% of patients progression free at 1 year. The median survival time and 2-year overall survival rate were 12.6 months and 27%, respectively. Treatment was generally well tolerated, with a toxicity profile as predicted based on the known toxicities of each treatment component.

Conclusions. Empiric treatment with paclitaxel, carboplatin, bevacizumab, and erlotinib is effective and well tolerated as first-line treatment for patients with CUP. Further development of this regimen is warranted.