PHASE-II TRIAL OF ISOTRETINOIN AND INTERFERON ALPHA-2A IN THE TREATMENT OF ADVANCED RECURRENT CERVICAL-CARCINOMA

Background: A recent trial by Lippman et al.((16)) demonstrated the effectiveness and synergy of the combination of interferon alpha-2a and isotretinoin in the treatment of patients with locally advanced, previously untreated squamous cell carcinoma of the cervix. Purpose: In this phase II trial, we used this combination to treat patients with advanced and recurrent squamous cell cervical carcinoma, aiming to assess its efficacy in terms of objective responses as well as toxicity. Methods: Eighteen patients with advanced recurrent squamous cell carcinoma of the cervix were enrolled. All 18 had previously been irradiated. In addition, six had received chemotherapy following progression after radiation therapy. Treatment consisted of interferon alpha-2a, 6 MU m(-2) subcutaneously daily, 5 days a week and isotretinoin, 1 mg kg(-1) orally, daily, for at least 2 months, depending on the response or toxicity. Results: All 18 patients (16 stage IVA and 2 stage IVB) were considered eligible for response and toxicity evaluation. After a median of 3 months (maximum of 8, in responders), we observed partial responses in two patients (11%); 95% confidence interval 0-25%. Five (27.7%) patients had stable disease. Responses and disease stabilization were observed only in the group of patients who had received irradiation alone. The median time to progression was 6 months (range 3-8+ months). The toxicity was very acceptable in this group of women. Low fever occurred at the beginning of the treatment in five patients. Fatigue and weakness were observed in four patients and required temporary interferon dose reduction, bone pain in three patients, grade 1 leukopenia in two patients and more intensive dry skin in four patients. Two patients had slight hypertriglyceridemia. Conclusion: Objective responses were observed using the combination of interferon alpha-2a and isotretinoin in a group of patients with advanced recurrent squamous cell carcinoma of the cervix. We now test this combination in previously untreated patients in a neoadjuvant setting.