13-cis-Retinoic Acid or All-trans-Retinoic Acid plus Interferon-α in Recurrent Cervical Cancer: A Southwest Oncology Group Phase II Randomized Trial

• Published in: Gynecologic oncology 1998-12, Vol.71 (3), p.386-390
• Main Authors: Weiss, Geoffrey R., Liu, P.Y., Alberts, David S., Peng, Yei-Mei, Fisher, Emily, Xu, Min Jian, Scudder, Sidney A., Baker, Laurence H., Moore, Dennis F., Lippman, Scott M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Biological and medical sciences; Carcinoma, Squamous Cell - drug therapy; Chemotherapy; Female; Humans; Interferon-alpha - therapeutic use; Isotretinoin - therapeutic use; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Pharmacology. Drug treatments; Tretinoin - therapeutic use; Uterine Cervical Neoplasms - drug therapy
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1006/gyno.1998.5204

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-cis-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 × 106units/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.