Halme M, Knuuttila A, Vehmas T, Tammilehto L, Mäntylä M, Salo J, Mattson K
Department of Medicine, Helsinki University Central Hospital, Finland.
Br J Cancer. 1999 Aug;80(11):1781-5. doi: 10.1038/sj.bjc.6690597.
Twenty six patients with pleural mesothelioma of UICC stage I-IV excluding M1 disease (46% of whom had stage I disease and 38% stage III disease) were treated intravenously with high dose MTX (3 g) and calcium folinate rescue three times at intervals of 2 weeks and three times at intervals of 3 weeks. Natural interferon (IFN)-alpha (3 MIU days 2-10) and recombinant IFN-gamma1b (50 microg m(-2) on days 2, 6 and 10) were injected subcutaneously after each MTX dose. At the end of MTX treatment the IFNs were continued as maintenance therapy until disease progression. Seven partial responses were observed among 24 patients evaluable for response (response rate 29%, 95% confidence interval 13-51%). Median duration of response was 10 months (range 3-24 months). Median survival was 17 months and 1-year and 2-year survival rates 62% and 31% respectively. The toxicity of the chemo-immunotherapy was acceptable. Treatment was stopped in one patient who developed grade IV neurological toxicity. MTX dose reductions were rare (two patients with grade 1-2 renal toxicity). The combination of high dose MTX and IFN-alpha and IFN-gamma is active against malignant pleural mesothelioma and well-tolerated. The survival rates are encouraging.
26例国际抗癌联盟（UICC）I - IV期（不包括M1期）胸膜间皮瘤患者（其中46%为I期疾病，38%为III期疾病）接受了高剂量甲氨蝶呤（MTX，3g）静脉治疗，并在2周间隔时给予亚叶酸钙解救3次，3周间隔时给予3次。每次MTX给药后皮下注射天然干扰素（IFN）-α（第2 - 10天，3MIU）和重组IFN-γ1b（第2、6和10天，50μg m(-2)）。在MTX治疗结束后，IFN继续作为维持治疗直至疾病进展。在24例可评估反应的患者中观察到7例部分缓解（缓解率29%，95%置信区间13 - 51%）。中位缓解持续时间为10个月（范围3 - 24个月）。中位生存期为17个月，1年和2年生存率分别为62%和31%。化疗免疫疗法的毒性是可接受的。1例出现IV级神经毒性的患者停止了治疗。MTX剂量减少情况罕见（2例1 - 2级肾毒性患者）。高剂量MTX与IFN-α和IFN-γ联合对恶性胸膜间皮瘤有效且耐受性良好。生存率令人鼓舞。
