Annals of Oncology Advance Access published online on May 7, 2008
Annals of Oncology, doi:10.1093/annonc/mdn174
Results from a monocentric phase II trial of erlotinib in patients with metastatic prostate cancer
1 Department of Medical Oncology, Institut Paoli-Calmettes
2 INSERM UMR 599
3 Université de la Méditerranée, UFR Médecine
4 Department of Urology, CHRU Marseille, Hôpital Sainte Marguerite
5 Department of Radiotherapy Oncology
6 Department of Biostatistic
7 Department of Surgery
8 Department of Anatomo-Pathology
9 Department of Radiology, Institut Paoli-Calmettes, Marseille, France
* Corresponding to: Dr G. Gravis, Institut Paoli-Calmettes, 232 Boulevard de Sainte Marguerite, 13009 Marseille, France. Tel: +33-4-91-22-37-40; Fax: +33-4-91-22-36-18; E-mail: gravisg{at}marseille.fnclcc.fr
Background: Erlotinib is an orally active small-molecule tyrosine kinase inhibitor targeted against human epidermal growth factor receptor 1/epidermal growth factor receptor (ErbB1), known to be overexpressed in a variety of cancers, including prostate cancer.
Patients and methods: This was a phase II monocentric study of 30 patients with advanced or metastatic prostate cancer, 29 had castration-resistant prostate cancer and 23 had received prior chemotherapy. Patients received erlotinib: 150 mg/day, increased to 200 mg at week 4, and continued until progression or unacceptable toxicity. Efficacy was defined as a decrease or stabilization of prostate-specific antigen (PSA) without clinical progression. Clinical benefit was evaluated by Karnofsky performance status and pain intensity, and response was an improvement in one of these parameters without worsening in the other.
Results: Median age was 69 years (range 51–77 years), and median PSA 102 ng/ml (range 3–1213 ng/ml). Dose escalation to 200 mg was possible in 16 (55%) patients. Moderate toxicity was observed. No patient had a decrease in PSA, 14% had stabilization, less than the 
20% expected. PSA-doubling time, evaluated before and after erlotinib, was increased for 10 patients (P = 0.0058). Clinical benefit was achieved in 40% of patients.
Conclusion: Erlotinib demonstrated an improvement in clinical benefit. Future directions should include evaluating its use in less advanced prostate cancer.
castration-resistant prostate cancer, clinical benefit, metastatic prostate cancer, tyrosine kinase inhibitor
Received for publication December 12, 2007. Revision received March 14, 2008. Revision received March 20, 2008. Accepted for publication March 26, 2008.