Phase II randomized controlled trial of radiation therapy plus concurrent interferon-alpha and retinoic acid versus cisplatin for stage III cervical carcinoma
Mené sur 104 patientes atteintes d'un cancer du col de l'utérus de stade III et sur 105 témoins (durée médiane de suivi : 29,2 mois), cet essai de phase II évalue, du point de vue de la survie globale à 3 ans et de la toxicité, l'intérêt d'un traitement combinant de manière concomitante une radiothérapie, l'interféron alpha-2b et l'acide 13-cis-rétinoïque par rapport à une chimioradiothérapie utilisant le cisplatine
Purpose : As a combination of retinoic acid, interferon-alpha and radiation demonstrated synergistic action and effectiveness to treat advanced cervical cancers in earlier studies,we designed this randomized phase II open-labeled trial toassess efficacy and safety of interferon alpha-2b (IFN) and 13-cis-retinoic acid (RA) administered concomitantly with radiotherapy to treat stage III cervical cancer. Methods and Materials : Stage III cervical cancer patients were randomized to study and control groups in a 1:1 ratio. All patients were treated with radiation-therapy; the study arm patients received IFN (3x106 IU subcutaneously) 3 times a week for four weeks and daily RA (40 mg orally) for 30 days starting on day 1 of radiation, while those in the control arm received weekly cisplatinum (40 mg/m2) for five weeks during radiation. Patients were followed for three years. The primary endpoint was overall survival at three years. The study was registered with Clinical Trials Registry (ClinicalTrials.gov Identifier: ----). Results : Patients in the study (N=104) and control (N=105) groups were comparable for clinico-pathological characteristics, radiation-therapy related variables and treatment response. The proportions of disease-free patients in the study and control groups were 38.5% and 44.8%, respectively, after median follow-up of 29.2 months. Hazard ratios of 0.67 (95%CI: 0.44-1.01) and 0.69 (95%CI: 0.44-1.06) for overall and disease-fee survival, respectively, comparing the study group to control, demonstrated an inferior outcome with RA-IFN-radiation, though the difference was statistically non-significant. Kaplan Meier curves of disease-free and overall survival probabilities also showed inferior survival in the study group compared to the control. Acute toxicities of chemo-radiation were significantly higher with two acute toxicity-related deaths. Conclusions : Treatment with RA-IFN-radiation did not demonstrate survival advantage over chemo-radiation in spite of being less toxic. The trends predict an inferior outcome with the RA-IFN combination.