By Bruce Sylvester
CHICAGO -- June 5, 2008 -- Combination treatment with erlotinib and cisplatin plus radiotherapy (RT) for patients with locally advanced squamous-cell cervical cancer (SCCC) achieves higher complete response rates compared with rates achieved historically with cisplatin plus radiotherapy, researchers reported here at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting.
"In this phase 2 study, we treated patients with very advanced disease, and the results show the current standard of care -- cisplatin plus radiotherapy -- to be suboptimal compared to the numbers achieved with the addition of erlotinib," said Angelica Rodrigues, MD, National Cancer Institute of Brazil, Rio de Janeiro, Brazil, in a presentation on May 31.
Erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, is currently approved in the United States as monotherapy for patients with locally advanced or metastatic non-small-cell lung cancer after failure of at least 1 prior chemotherapy regimen, according to Dr. Rodrigues and colleagues.
Preclinical data show that inhibition of EGFR enhances the effect of cisplatin and RT, the investigators noted. They previously reported the results of a phase 1 study which determined the maximal tolerated dose of erlotinib at 150 mg/day for the combination treatment of locally advanced SCCC.
The phase 2 study included patients with histologically proven, stage IIB to IIIB disease, and no prior therapy, as well as an Easter Cooperative Oncology Group performance status <3, and adequate end-organ functions.
Subjects received erlotinib 150 mg/day 1 week before cisplatin then in combination with cisplatin 40 mg/m2 weekly in 5 cycles, and external beam RT 4,500 cGy in 25 fractions, followed by 4 fractions of brachytherapy 600 cGy weekly.
The researchers enrolled 36 subjects between February 2006 and January 2008. Subjects had a median age of 45 years (range, 28-68); disease stages were IIB (55%), IIIA (3%), and IIIB (42%). Two subjects did not complete the planned treatment.
Overall, the combination of erlotinib, cisplatin, and RT was well tolerated, the researchers said.
Of the 34 subjects who completed treatment, median duration of treatment was 77 days (range, 64-106).
Of the 34 subjects evaluable for response, 7 have not yet completed the 3-month interval for response evaluation.
The 27 evaluated subjects underwent clinical exam, magnetic resonance imaging, computed tomography (CT) scan, and positron emission tomography CT scan.
Results show that 25 subjects (92.6%; confidence interval [CI] 95%, 74.2%-98.7%) achieved a complete response, and 2 subjects (7.4%) had a partial response.
After a median follow-up of 13.8 months, none of the subjects had disease progression.
"The findings show that the new combination is worth testing in a randomised, clinical trial," Dr. Rodrigues added.
[Presentation title: Erlotinib (E) Combined With Cisplatin (C) and Radiotherapy (RT) for Patients With Locally Advanced Squamous Cell Cervical Cancer: A Phase II Trial. Abstract 5511]
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