Phase 2 Randomized Controlled Trial of Radiation Therapy Plus Concurrent Interferon-Alpha and Retinoic Acid Versus Cisplatin for Stage III Cervical Carcinoma

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• 作者：Partha Basu ; MD^&lowast ; ; ^{BasuP@iarc.fr" class="auth_mail" title="E-mail the corresponding author} ; Alfred Bennett Jenson ; MS ; MD^&dagger ; ; Tapas Majhi ; MD^&Dagger ; ; Prabir Choudhury ; DNB^&Dagger ; ; Ranajit Mandal ; MD^§ ; ; Dipanwita Banerjee ; MS^§ ; ; Jaydip Biswas ; MS^‖ ; Jianmin Pan ; PhD^&dagger ; ; Shesh Nath Rai ; PhD^&dagger ; ; Shin je Ghim ; PhD^&dagger ; ; Donald Miller ; MD ; PhD^&dagger ;
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：2016
• 出版时间：1 January 2016
• 年：2016
• 卷：94
• 期：1
• 页码：102-110
• 全文大小：431 K

文摘

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 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; study arm patients received IFN (3 × 10⁶ 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/m²) 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.