13-cis-Retinoic Acid Plus Interferon α -2a: Highly Active Systemic Theraphy for Squamous Cell Carcinoma of the Cervix
13-cis-Retinoic Acid Plus Interferon α -2a: Highly Active Systemic Theraphy for Squamous Cell Carcinoma of the Cervix
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13-顺式视黄酸加干扰素α-2a：宫颈鳞状细胞癌的高效全身治疗
DOI：
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发表时间：
1992
期刊：
影响因子：
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通讯作者：
I. Krakoff
中科院分区：
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作者：
S. Lippman;J. Kavanagh;M. Paredes;F. Delgadillo;P. Paredes;W. Hong;Eduardo Holderner;I. Krakoff
背景宫颈鳞状细胞癌的化学研究已显示出一些积极的结果。在晚期疾病患者中使用少量细胞毒性单药可实现15%-35%的完全加部分（总体）缓解率（完全缓解率，小于5%）。此外，在原发性局部晚期疾病患者中，以顺铂为基础的多药方案的总体缓解率为60%-70%（完全缓解率为10%-20%）。然而，缺乏明确的证据表明，现有的化疗可以实现生存的好处，加上全球每年有数十万妇女死于宫颈癌，表明迫切需要有效的全身治疗这种疾病。鉴于临床前和临床证据支持在宫颈鳞状细胞癌中测试13-顺式-维甲酸（13-cRA）加干扰素-α（IFN-α）的新组合，我们在局部晚期疾病中进行了该方案的II期研究。方法26例未经治疗的局部晚期宫颈鳞状细胞癌患者每天口服13-cRA（1 mg/kg）和皮下注射重组人IFN α-2a（6百万单位），至少持续2个月。在21例患者（81%）中，疾病为II期或更高。结果：13例患者（50%）经历了与症状消退相关的主要反应（肿瘤消退大于或等于50%）; 1例获得完全反应，12例获得部分反应。7例部分缓解患者正在进一步改善，4例维持部分缓解，1例缓解者在治疗期间复发。在IIB期或以上疾病患者中，缓解率为58%（11/19），在巨大疾病（至少一个尺寸大于或等于10 cm）患者中，缓解率为66%（10/15）。在13名无应答者中，9名患者病情稳定，4名患者在治疗期间病情进展。毒性很小。结论13-cRA联合IFN α-2a治疗局部晚期宫颈癌疗效肯定，耐受性好。
BACKGROUND Chemotherapeutic study of cervical squamous cell carcinoma has shown some positive results. Complete plus partial (overall) response rates of 15%-35% (complete response rate, less than 5%) were achieved with the use of a small number of cytotoxic single agents in patients with advanced disease. In addition, overall response rates of 60%-70% (complete response rates, 10%-20%) were achieved with cisplatin-based, multiagent regimens in patients with primary, locally advanced disease. However, the lack of clear evidence that existing chemotherapy can achieve a survival benefit, coupled with the worldwide annual deaths of hundreds of thousands of women from cervical cancer, indicates the urgent need for effective systemic therapy for this disease. PURPOSE In view of the preclinical and clinical evidence that supports testing of the novel combination of 13-cis-retinoic acid (13-cRA) plus interferon-alpha (IFN-alpha) in cervical squamous cell carcinoma, we conducted a phase II study of this regimen in locally advanced disease. METHODS Twenty-six patients with untreated, locally advanced squamous cell carcinoma of the cervix were treated daily for at least 2 months with oral 13-cRA (1 mg/kg) and subcutaneous recombinant human IFN alpha-2a (6 million units). In 21 patients (81%), the disease was stage II or higher. RESULTS Thirteen patients (50%) experienced major responses (tumor regression greater than or equal to 50%) in association with resolution of symptoms; one achieved complete response, and 12 experienced partial response. Seven with partial response are improving further, four are being maintained in partial response, and one responder has relapsed during therapy. The response rate is 58% (11 of 19) in patients with stage IIB or higher disease and 66% (10 of 15) in patients with bulky disease (at least one dimension greater than or equal to 10 cm). Of the 13 non-responders, nine have stable disease and four have had disease progression during therapy. Toxicity was minimal. CONCLUSION These preliminary results indicate that systemic 13-cRA plus IFN alpha-2a is a highly active, well-tolerated therapy for locally advanced cervical cancer.