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

Gynecol Oncol. 1998 Dec;71(3):386-90. doi: 10.1006/gyno.1998.5204.

Abstract

Purpose: Preclinical and clinical data support the study of retinoids and interferon-alpha (IFN-alpha) 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-alpha 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-alpha-2A (subcutaneous injection; 3 x 10(6) 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-alpha response rate was 5% (1/19; 95% confidence interval = 0.1-26%), consisting of 1 partial response lasting 4 weeks. The 13cRA/IFN-alpha 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / drug therapy*
  • Female
  • Humans
  • Interferon-alpha / therapeutic use*
  • Isotretinoin / therapeutic use*
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Tretinoin / therapeutic use*
  • Uterine Cervical Neoplasms / drug therapy*

Substances

  • Interferon-alpha
  • Tretinoin
  • Isotretinoin