Medical Oncology Department, Istituto Oncologico Veneto, Via Gattamelata 64, I-35128 Padua, Italy.
Lung Cancer. 2011 Sep;73(3):351-5. doi: 10.1016/j.lungcan.2011.01.005. Epub 2011 Feb 5.
The major clinical problems of MPM management are the short duration of response and the early relapse. Currently, after the first-line standard pemetrexed/platinum combination there is not a defined regimen for the second line treatment of MPM, and the clinical benefits in fit patients are uncertain. We analyzed the feasibility of gemcitabine/platinum chemotherapy in pretreated MPM patients.
Eligible patients should have relapsed after first-line chemotherapy with pemetrexed plus cisplatin (24%) or carboplatin (76%); 53% of the patients had previously received trimodality treatment, 18% neoadjuvant chemotherapy followed by pleurectomy/decortication, 29% were inoperable. Patients had to have PS=0-2, adequate organ function, measurable disease. Chemotherapy was gemcitabine 1000 mg/m(2) days 1, 8 associated to the alternative platinum compound respect to 1st line, i.e. cisplatin 75 mg/m(2) or carboplatin AUC 5 day 1 every 3 weeks, for 3-6 cycles. Baseline staging and reassessment after cycles 3 and 6 were performed with CT-scan.
Since 2006 17 relapsed MPM patients were referred to our centre. Patients were 12 males and 5 females; median age: 61 years (range 47-74); histology: 12 epithelial, 4 sarcomatoid and 1 biphasic. PS 1-2 (15:2). The combination of gemcitabine with carboplatin/cisplatin was administered as second line treatment in 13 (76%) patients, as third line in 4 (24%) patients. Two patients were lost to follow-up without re-evaluation, therefore radiologic and clinical response was assessable in 15 (88%) patients. Among evaluable patients 10 (67%) showed stable disease and 5 (33%) progressive disease. Symptoms improved in 8 (53%) cases. In the intent-to-treat population median survival was 28 weeks (range 13-168) and median time-to-treatment failure 15 weeks (range 3-75). Toxicity profile showed 2 (13%) grade 4 and 6 (40%) grade 3 thrombocytopenia, 4 (27%) grade 3 leucopenia, 3 (20%) grade 3 anaemia and 6 (40%) of grade 3 neutropenia. Grade 3 non haematological toxicities were nausea (14%) and asthenia (21%).
Gemcitabine-platinum regimens are able to control symptoms and disease progression with a modest toxicity profile. The present results from a small series of patients should be confirmed by a prospective trial in a larger cohort of patients.
间皮瘤（MPM）管理的主要临床问题是反应持续时间短和早期复发。目前，在一线标准培美曲塞/铂类联合治疗后，对于 MPM 的二线治疗尚无明确方案，并且在适合的患者中临床获益不确定。我们分析了吉西他滨/铂类化疗在预处理 MPM 患者中的可行性。
符合条件的患者应在接受培美曲塞联合顺铂（24%）或卡铂（76%）的一线化疗后复发；53%的患者之前接受过三联疗法治疗，18%接受过新辅助化疗加胸膜切除术/剥脱术，29%的患者无法手术。患者 PS=0-2，器官功能正常，有可测量的疾病。化疗采用吉西他滨 1000mg/m2，第 1、8 天给药，联合与一线治疗不同的铂类化合物，即顺铂 75mg/m2 或卡铂 AUC5，第 1 天，每 3 周一次，共 3-6 个周期。在第 3 周期和第 6 周期后进行基线分期和评估，并进行 CT 扫描。
自 2006 年以来，17 名复发的 MPM 患者被转介到我们中心。患者为 12 名男性和 5 名女性；中位年龄：61 岁（范围 47-74 岁）；组织学：12 例上皮，4 例肉瘤样，1 例双相。PS 1-2（15：2）。13 例（76%）患者以吉西他滨联合卡铂/顺铂作为二线治疗，4 例（24%）患者作为三线治疗。2 例患者失访未进行重新评估，因此 15 例（88%）患者可评估影像学和临床反应。在可评估的患者中，10 例（67%）患者疾病稳定，5 例（33%）患者疾病进展。8 例（53%）患者症状改善。在意向治疗人群中，中位生存期为 28 周（范围 13-168 周），中位治疗失败时间为 15 周（范围 3-75 周）。毒性谱显示 2 例（13%）为 4 级血小板减少症，6 例（40%）为 3 级血小板减少症，4 例（27%）为 3 级白细胞减少症，3 例（20%）为 3 级贫血，6 例（40%）为 3 级中性粒细胞减少症。3 级非血液学毒性为恶心（14%）和乏力（21%）。
吉西他滨-铂类方案能够控制症状和疾病进展，且毒性谱适中。目前这一来自小系列患者的结果应在更大的患者队列中通过前瞻性试验得到证实。
