13-cis-retinoic acid or all-trans-retinoic acid plus inteferon-alpha in recurrent cervical cancer: A Southwest Oncology Group phase II randomized trial

Purpose. Preclinical and clinical data support the study of retinoids and i nterferon-alpha (IFN-alpha) in advanced squamous cell carcinoma of the uter ine cenix (SCC). This phase II randomized trial of the Southwest Oncology G roup sought to estimate the response rate for IFN-alpha plus either 13-cis- retinoic acid (13cRA) or all-trans-retinoic acid (ATRA) in women with recur rent cervical SCC, Patients and Methods. Eligibility for this trial required bidimensionally m easurable locally recurrent or metastatic squamous or adenosquamous carcino ma of the uterine cervix; SWOG performance status of less than or equal to 2; no prior interferon, retinoids, or chemotherapy (except as radiation sen sitization), All but two patients were previously treated with surgery, rad iation therapy, or both. After randomization, patients received IFN-alpha-2 A (subcutaneous injection; 3 x 10(6) units/m(2)/day) plus either 13cRA (1 m g/kg/day orally) or ATRA (150 mg/m(2)/day orally) in two equally divided do ses. Results. Total enrollment was 63 patients, 21 in the ATRA arm, 42 in the 13 cRA arm. Three patients were ineligible, 1 in the ATRA arm, 2 in the 13cRA arm, Each arm had 1 patient who received no assigned treatment and was not evaluated for response or toxicity. The ATRA/IFN-alpha response rate was 5% (1/19; 95% confidence interval = 0.1-26%), consisting of 1 partial respons e lasting 4 weeks. The 13cRA/IFN-alpha response rate was 8% (3/39; 95% conf idence interval = 2-21%), consisting of 3 partial responses lasting 17, 22, and 24 weeks, respectively. All confirmed responses were partial. One addi tional unconfirmed partial response occurred in the 13cRA arm. Both regimen s were generally well-tolerated and produced toxicities (principally malais e and fatigue) associated with each constituent agent's known single-agent side effects. Conclusion. Based upon the results of this study, neither regimen can be re commended for further study in patients previously treated with radiation t herapy. (C) 1998 Academic Press.