Efficacy and safety of erlotinib HCl, an epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor, in patients with advanced ovarian carcinoma: results from a phase II multicenter study

The aim of this single-arm, phase II study was to estimate the tumor response rate and safety profile of erlotinib HCl (erlotinib, Tarceva™, OSI-774) monotherapy in patients with refractory, recurrent, HER1/EGFR-positive epithelial ovarian tumors, who had failed prior taxane and/or platinum-based chemotherapy. Thirty-four patients received 150 mg erlotinib orally once daily for up to 48 weeks or until disease progression or dose-limiting toxicity. Two patients had partial responses, lasting 8+ and 17 weeks, giving an objective response rate of 6% (95% confidence interval [CI], 0.7–19.7%). Fifteen patients (44%) had stable disease, and 17 patients (50%) had progressive disease. Median overall survival was 8 months (95% CI, 5.7–12.7 months), with a 1-year survival rate of 35.3% (95% CI, 19.8–53.5%). Patients with rash survived significantly longer than those without (P = 0.009), correlating with rash grade. Erlotinib was generally well tolerated. The most frequent erlotinib-related adverse events were rash (68%) and diarrhea (38%). Erlotinib had marginal activity but was generally well tolerated. The safety profile appears more favorable than typically experienced with standard chemotherapeutic agents, which is encouraging in these heavily pretreated patients. Combination of erlotinib with chemotherapy or other targeted agents should be considered.

[1]  Alicia Samuels,et al.  Cancer Statistics, 2003 , 2003, CA: a cancer journal for clinicians.

[2]  C. Dunton Management of treatment-related toxicity in advanced ovarian cancer. , 2002, The oncologist.

[3]  D. Armstrong Relapsed ovarian cancer: challenges and management strategies for a chronic disease. , 2002, The oncologist.

[4]  R. Nicholson,et al.  EGFR and cancer prognosis. , 2001, European journal of cancer.

[5]  E K Rowinsky,et al.  Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  B. Goff,et al.  Ovarian carcinoma diagnosis , 2000, Cancer.

[7]  M. Piccart,et al.  Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. , 2000, Journal of the National Cancer Institute.

[8]  Ozols Rf Update of the NCCN ovarian cancer practice guidelines , 1997 .

[9]  L. Pustilnik,et al.  Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. , 1997, Cancer research.

[10]  T. Bauknecht,et al.  Carboplatin/paclitaxel versus cisplatin/paclitaxel as first-line chemotherapy in advanced ovarian cancer: an interim analysis of a randomized phase III trial of the Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group. , 1997, Seminars in oncology.

[11]  G. Prins,et al.  Expression of epidermal growth factor and androgen receptors in ovarian cancer. , 1997, Gynecologic oncology.

[12]  R. Ozols Update of the NCCN ovarian cancer practice guidelines. , 1997, Oncology.

[13]  P. Sismondi,et al.  The prognostic value of epidermal growth factor receptor mRNA expression in primary ovarian cancer. , 1996, British Journal of Cancer.

[14]  E. Partridge,et al.  Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer , 1996, New England Journal of Medicine.

[15]  A. Gown,et al.  Overexpression and relationships of HER-2/neu, epidermal growth factor receptor, p53, Ki-67, and tumor necrosis factor alpha in epithelial ovarian cancer. , 1996, European journal of gynaecological oncology.

[16]  G. Scambia,et al.  Epidermal growth factor, oestrogen and progesterone receptor expression in primary ovarian cancer: correlation with clinical outcome and response to chemotherapy. , 1995, British Journal of Cancer.

[17]  J. Thigpen,et al.  Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic Oncology Group study. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  P. Davaris,et al.  Immunohistochemical expression of EGF-R in malignant surface epithelial ovarian neoplasms (SEON). , 1994, European journal of gynaecological oncology.

[19]  R Yancik,et al.  Ovarian cancer. Age contrasts in incidence, histology, disease stage at diagnosis, and mortality. , 1993, Cancer.

[20]  J. Foekens,et al.  The prognostic value of epidermal growth factor receptors, determined by both immunohistochemistry and ligand binding assays, in primary epithelial ovarian cancer: a pilot study. , 1993, European journal of cancer.

[21]  R. Bast,et al.  Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. I. Correlation of receptor expression with prognostic factors in patients with ovarian cancer. , 1991, American journal of obstetrics and gynecology.

[22]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.