title: Phase 2 Randomized Controlled Trial of Radiation Therapy Plus Concurrent Interferon-Alpha and Retinoic Acid Versus Cisplatin for Stage III Cervical Carcinoma.
abstract: OBJECTIVE
  Because a combination of retinoic acid, interferon-alpha, and radiation therapy demonstrated synergistic action and effectiveness to treat advanced cervical cancers in earlier studies, we designed this randomized phase 2 open-label trial to assess efficacy and safety of interferon alpha-2b (IFN) and 13-cis-retinoic acid (RA) administered concomitantly with radiation therapy (IFN-RA-radiation) to treat stage III cervical cancer.
  
  
  METHODS
  Stage III cervical cancer patients were randomized to study and control groups in a 1:1 ratio. All patients were treated with radiation therapy; study arm patients received IFN (3 × 10(6) IU subcutaneously) 3 times a week for 4 weeks and daily RA (40 mg orally) for 30 days starting on day 1 of radiation, whereas control arm patients received weekly cisplatinum (40 mg/m(2)) for 5 weeks during radiation. Patients were followed for 3 years. The primary endpoint was overall survival at 3 years.
  
  
  RESULTS
  Patients in the study (n=104) and control (n=105) groups were comparable for clinicopathological characteristics, radiation therapy-related variables and treatment response. 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 were 0.67 (95% confidence interval [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, and demonstrated an inferior outcome with RA-IFN-radiation, although differences were statistically nonsignificant. Kaplan-Meier curves of disease-free and overall survival probabilities also showed inferior survival in the study group compared to those in the control. Acute toxicities of chemoradiation were significantly higher with 2 acute toxicity-related deaths.
  
  
  CONCLUSIONS
  Treatment with RA-IFN-radiation did not demonstrate survival advantage over chemoradiation despite being less toxic. The trends predicted an inferior outcome with the RA-IFN combination.
authors.affiliation: Screening Group, Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France. Electronic address: BasuP@iarc.fr.
authors.forename: Partha
authors.initials: P
authors.lastname: Basu
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
authors.forename: Alfred Bennett
authors.initials: AB
authors.lastname: Jenson
authors.affiliation: Department of Radiation Oncology, Chittaranjan National Cancer Institute, Kolkata, India.
authors.forename: Tapas
authors.initials: T
authors.lastname: Majhi
authors.affiliation: Department of Radiation Oncology, Chittaranjan National Cancer Institute, Kolkata, India.
authors.forename: Prabir
authors.initials: P
authors.lastname: Choudhury
authors.affiliation: Department of Gynecological Oncology, Chittaranjan National Cancer Institute, Kolkata, India.
authors.forename: Ranajit
authors.initials: R
authors.lastname: Mandal
authors.affiliation: Department of Gynecological Oncology, Chittaranjan National Cancer Institute, Kolkata, India.
authors.forename: Dipanwita
authors.initials: D
authors.lastname: Banerjee
authors.affiliation: Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata, India.
authors.forename: Jaydip
authors.initials: J
authors.lastname: Biswas
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Pan
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
authors.forename: Shesh Nath
authors.initials: SN
authors.lastname: Rai
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
authors.forename: Shin Je
authors.initials: SJ
authors.lastname: Ghim
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
authors.forename: Donald
authors.initials: D
authors.lastname: Miller
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001918:Brachytherapy; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D014212:Tretinoin / Q000008:administration & dosage; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014212:Tretinoin; D002945:Cisplatin