Goldman C A, Skinnider L F, Maksymiuk A W
Durban Oncology Centre, Addington Hospital, Republic of South Africa.
Ann Oncol. 1993 Feb;4(2):141-5. doi: 10.1093/oxfordjournals.annonc.a058416.
Malignant pleural effusions can be managed in various ways including instillation of antineoplastic agents. Instillations of alfa interferon-2b (IFN-alpha 2b) have been utilized with success in various loco-regional malignancies suggesting a possible role in management of pleural effusions. This trial was designed to evaluate the tolerability and efficacy of intrapleural IFN-alpha 2b instillations in this situation.
Twenty-three patients with cytologically proven malignant pleural effusions were given IFN-alpha 2b 50 x 10(6) units in 50 ml normal saline (NS) by intrapleural instillation after partial or complete clearance of effusions by percutaneous aspiration or chest tube drainage. For persistent or recurrent effusions, instillations were repeated with dose escalation to 75 x 10(6) units. Patients were assessed and monitored by regular clinical examinations, chest radiographs, biochemical and hematological parameters and assays of lymphocyte subpopulations until relapse or death in each case.
Fourteen of 20 evaluable patients (70%) had responses lasting for a median of 6 months; there were 8 complete responses (CR) and 6 partial responses (PR). In 6 CR patients the effusions did not recur after the first instillation. In 2 of 6 other patients, the second instillation was successful in inducing CR. Intrapleural instillation of IFN-alpha 2b was well tolerated, no grade 4 toxicities were encountered. There were no significant effects on any of the studied parameters at the initial dose level; however, grade 3 neutropenia occurred with the escalated dose. The most common toxicity was flu-like syndrome, after 70% of the instillations.
Intrapleural instillation of IFN-alpha 2b produced an encouraging response rate without significant toxicities. This approach may warrant additional phase II or phase III comparative clinical studies.
恶性胸腔积液可有多种处理方式，包括抗肿瘤药物的胸腔内注入。α-干扰素2b（IFN-α 2b）注入已成功应用于多种局部区域恶性肿瘤，提示其在胸腔积液处理中可能发挥作用。本试验旨在评估在此情况下胸腔内注入IFN-α 2b的耐受性和疗效。
23例经细胞学证实的恶性胸腔积液患者，在经皮穿刺抽吸或胸腔闭式引流部分或完全清除胸腔积液后，通过胸腔内注入50ml生理盐水（NS）中的50×10⁶单位IFN-α 2b。对于持续性或复发性胸腔积液，重复注入并将剂量增至75×10⁶单位。通过定期临床检查、胸部X线片、生化和血液学参数以及淋巴细胞亚群检测对患者进行评估和监测，直至每例患者复发或死亡。
20例可评估患者中有14例（70%）有反应，持续时间中位数为6个月；有8例完全缓解（CR）和6例部分缓解（PR）。在6例CR患者中，首次注入后胸腔积液未复发。在另外6例患者中的2例，第二次注入成功诱导了CR。胸腔内注入IFN-α 2b耐受性良好，未出现4级毒性反应。在初始剂量水平对任何研究参数均无显著影响；然而，剂量增加后出现了3级中性粒细胞减少。最常见的毒性反应是类流感综合征，70%的注入后出现。
胸腔内注入IFN-α 2b产生了令人鼓舞的反应率且无明显毒性。这种方法可能值得进行更多的II期或III期比较临床研究。
