13-cis-retinoic acid or All-trans-retinoic acid plus interferon-α in recurrent cervical cancer: A Southwest Oncology Group phase II randomized trial

Purpose. Preclinical and clinical data support the study of retinoids and interferon-α (IFN-α) in advanced squamous cell carcinoma of the uterine cervix (SCC). This phase II randomized trial of the Southwest Oncology Group sought to estimate the response rate for IFN-α plus either 13-c/s-retinoic acid (13cRA) or all-trans-retinoic acid (ATRA) in women with recurrent cervical SCC. Patients and Methods. Eligibility for this trial required bidimensionally measurable locally recurrent or metastatic squamous or adenosquamous carcinoma of the uterine cervix; SWOG performance status of ≤2; no prior interferon, retinoids, or chemotherapy (except as radiation sensitization). All but two patients were previously treated with surgery, radiation therapy, or both. After randomization, patients received IFN-α-2A (subcutaneous injection; 3 x 10⁶ units/m²/day) plus either 13cRA (1 mg/kg/day orally) or ATRA (150 mg/m²/day orally) in two equally divided doses. Results. Total enrollment was 63 patients, 21 in the ATRA arm, 42 in the 13cRA 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-α response rate was 5% (1/19; 95% confidence interval = 0.1-26%), consisting of 1 partial response lasting 4 weeks. The 13cRA/IFN-α response rate was 8% (3/39; 95% confidence interval = 2-21%), consisting of 3 partial responses lasting 17, 22, and 24 weeks, respectively. All confirmed responses were partial. One additional unconfirmed partial response occurred in the 13cRA arm. Both regimens were generally well-tolerated and produced toxicities (principally malaise 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 recommended for further study in patients previously treated with radiation therapy.