Screening Group, Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France.
James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
Int J Radiat Oncol Biol Phys. 2016 Jan 1;94(1):102-110. doi: 10.1016/j.ijrobp.2015.09.040.
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.
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.
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.
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.
由于先前的研究表明维甲酸、干扰素-α和放射治疗联合应用对治疗晚期宫颈癌具有协同作用和疗效，我们设计了这项随机 2 期开放标签试验，以评估干扰素-α-2b（IFN）和 13-顺式维甲酸（RA）与放射治疗（IFN-RA-放射治疗）同时用于治疗 III 期宫颈癌的疗效和安全性。
将 III 期宫颈癌患者按 1:1 的比例随机分为研究组和对照组。所有患者均接受放射治疗；研究组患者在放射治疗的第 1 天开始每周接受 3 次 IFN（3×106IU 皮下注射）和 4 周，每天口服 RA（40mg），持续 30 天；而对照组患者在放射治疗期间每周接受顺铂（40mg/m2）5 次。患者随访 3 年。主要终点是 3 年总生存率。
研究组（n=104）和对照组（n=105）患者的临床病理特征、放射治疗相关变量和治疗反应相当。在中位随访 29.2 个月后，研究组和对照组无病患者的比例分别为 38.5%和 44.8%。研究组和对照组的总生存率和无病生存率的危险比分别为 0.67（95%置信区间[CI]：0.44-1.01）和 0.69（95% CI：0.44-1.06），表明与对照组相比，RA-IFN-放射治疗的结果较差，尽管差异无统计学意义。无病生存和总生存概率的 Kaplan-Meier 曲线也显示研究组的生存情况较对照组差。放化疗的急性毒性明显较高，有 2 例与急性毒性相关的死亡。
尽管 RA-IFN-放射治疗的毒性较低，但与放化疗相比，并未显示出生存优势。这些趋势预示着 RA-IFN 联合治疗的结果较差。
