Astoul P, Viallat J R, Laurent J C, Brandely M, Boutin C
Department of Pulmonology, Hopital de la Conception, Marseille, France.
Chest. 1993 Jan;103(1):209-13. doi: 10.1378/chest.103.1.209.
The purpose of this phase 1 study was to determine the toxicity and effectiveness of recombinant interleukin-2 (RU 49637 Roussel Uclaf-France) administered by continuous pleural infusion for 5 days to patients with different histologic subtypes of pleural cancer. Incremental doses of rIL-2 from 3 x 10(6) to 24 x 10(6) were given via a thin catheter inserted into the homolateral pleural cavity. Patients were evaluated before treatment and 36 days after treatment by computed tomography scan and thoracoscopy with biopsy. Twenty-two patients with malignant pleural effusion (15 malignant pleural mesotheliomas, 6 adenocarcinomas, 1 squamous cell carcinoma) were treated. The maximum tolerated dose (MTD) of rIL-2, defined as the dose that produced grade 3 or greater toxic reactions in 50 percent of the patients, was 24 x 10(6) IU/m2/d. Although some side effects were encountered at any dose, tolerance was acceptable. The main side effect was fluid retention (8 of 22) which never exceeded 10 percent of body weight. Responses were achieved in 10 out of 22 patients with 1 complete remission (mesothelioma) and 9 partial remissions (3 adenocarcinomas and 6 malignant pleural mesotheliomas). Based on these results, we recommend that phase 2 studies using rIL-2 at a dose of 21 x 10(6) IU/m2/d via the intrapleural route be undertaken.
本1期研究的目的是确定通过持续胸膜内输注5天给予不同组织学亚型胸膜癌患者重组白细胞介素-2（RU 49637，法国罗素优克福公司）的毒性和有效性。通过插入同侧胸膜腔的细导管给予递增剂量的重组白细胞介素-2，剂量从3×10⁶至24×10⁶。在治疗前以及治疗后36天通过计算机断层扫描和胸腔镜活检对患者进行评估。对22例恶性胸腔积液患者（15例恶性胸膜间皮瘤、6例腺癌、1例鳞状细胞癌）进行了治疗。重组白细胞介素-2的最大耐受剂量（MTD）定义为在50%的患者中产生3级或更严重毒性反应的剂量，为24×10⁶IU/m²/天。尽管在任何剂量下都出现了一些副作用，但耐受性尚可。主要副作用是液体潴留（22例中有8例），从未超过体重的10%。22例患者中有10例有反应，其中1例完全缓解（间皮瘤），9例部分缓解（3例腺癌和6例恶性胸膜间皮瘤）。基于这些结果，我们建议采用经胸膜内途径以21×10⁶IU/m²/天的剂量使用重组白细胞介素-2进行2期研究。
