13-CIS-RETINOIC ACID PLUS INTERFERON ALPHA-2A - HIGHLY-ACTIVE SYSTEMIC THERAPY FOR SQUAMOUS-CELL CARCINOMA OF THE CERVIX
13-CIS-RETINOIC ACID PLUS INTERFERON ALPHA-2A - HIGHLY-ACTIVE SYSTEMIC THERAPY FOR SQUAMOUS-CELL CARCINOMA OF THE CERVIX
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DOI：
10.1093/jnci/84.4.241
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发表时间：
1992-02-19
影响因子：
10.3
通讯作者：
KRAKOFF, IH
中科院分区：
文献类型：
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作者：
LIPPMAN, SM;KAVANAGH, JJ;KRAKOFF, IH
背景：宫颈鳞状细胞癌的化疗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%（完全缓解率 < 5%）的完全加部分（总体）缓解率。此外，对于患有原发性局部晚期疾病的患者，基于顺铂的多药治疗方案实现了 60%-70% 的总体缓解率（完全缓解率为 10%-20%）。然而，缺乏明确的证据表明现有化疗可以实现生存获益，加上全世界每年有数十万妇女死于宫颈癌，表明迫切需要针对这种疾病进行有效的全身治疗。目的：鉴于支持在宫颈鳞状细胞癌中测试 13-顺式视黄酸 (13-cRA) 加干扰素-α (IFN-α) 的新型组合的临床前和临床证据，我们对该方案在局部晚期疾病中进行了 II 期研究。方法：26 名未经治疗的局部晚期宫颈鳞状细胞癌患者每天接受口服 13-cRA (1 mg/kg) 和皮下注射重组人 IFN α-2a（600 万单位）治疗，持续至少 2 个月。 21 名患者 (81%) 的疾病处于 II 期或更高阶段。结果：13 名患者 (50%) 经历了与症状消退相关的主要缓解（肿瘤消退 > 50%），其中 1 名患者实现了完全缓解，12 名患者经历了部分缓解。七名部分缓解的患者正在进一步改善，四名患者维持部分缓解，一名缓解者在治疗期间复发。对于 IIB 期或以上疾病的患者，缓解率为 58%（19 例中的 11 例）；对于大块疾病（至少一个尺寸大于或等于 10 厘米）的患者，缓解率为 66%（15 例中的 10 例）。在 13 名无反应者中，9 名病情稳定，4 名在治疗期间疾病进展。毒性很小。结论：这些初步结果表明，全身 13-cRA 加 IFN α-2a 是治疗局部晚期宫颈癌的一种高度有效、耐受性良好的疗法。
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, < 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 ill 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 > 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 nonresponders, 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.