13-CIS-RETINOIC ACID PLUS INTERFERON ALPHA-2A - HIGHLY-ACTIVE SYSTEMIC THERAPY FOR SQUAMOUS-CELL CARCINOMA OF THE CERVIX

Background: Chemotherapeutic study of cervical squamous cell carcinoma has shown some positive results. Complete plus partial (overall) response rates of 15%-35% (complete response rate, < 5%) were achieved with the use of a small number of cytotoxic single agents in patients with advanced disease. In addition, overall response rates of 60%-70% (complete response rates, 10%-20%) were achieved with cisplatin-based, multiagent regimens ill patients with primary, locally advanced disease. However, the lack of clear evidence that existing chemotherapy can achieve a survival benefit, coupled with the worldwide annual deaths of hundreds of thousands of women from cervical cancer, indicates the urgent need for effective systemic therapy for this disease. Purpose: In view of the preclinical and clinical evidence that supports testing of the novel combination of 13-cis-retinoic acid (13-cRA) plus interferon-alpha (IFN-alpha) in cervical squamous cell carcinoma, we conducted a phase II study of this regimen in locally advanced disease. Methods: Twenty-six patients with untreated, locally advanced squamous cell carcinoma of the cervix were treated daily for at least 2 months with oral 13-cRA (1 mg/kg) and subcutaneous recombinant human IFN alpha-2a (6 million units). In 21 patients (81%), the disease was stage II or higher. Results: Thirteen patients (50%) experienced major responses (tumor regression > 50%) in association with resolution of symptoms, one achieved complete response, and 12 experienced partial response. Seven with partial response are improving further, four are being maintained in partial response, and one responder has relapsed during therapy. The response rate is 58% (11 of 19) in patients with stage IIB or higher disease and 66% (10 of 15) in patients with bulky disease (at least one dimension greater-than-or-equal-to 10 cm). Of the 13 nonresponders, nine have stable disease and four have had disease progression during therapy. Toxicity was minimal. Conclusion: These preliminary results indicate that systemic 13-cRA plus IFN alpha-2a is a highly active, well-tolerated therapy for locally advanced cervical cancer.