Klein H O, Wickramanayake P D, Dieterle F, Mohr R, Oerkermann H, Gross R
Semin Oncol. 1983 Jun;10(2 Suppl 2):29-31.
In a phase II trial we tried to evaluate the efficacy of a sequential combination of high-dose methotrexate (MTX) and 5-fluorouracil (5-FU) combined with Adriamycin (ADM). In a pilot study we had found high-dose MTX effective as a single agent in gastric cancer. MTX and 5-FU were combined sequentially because Cadman et al had shown synergism for this combination. The therapy protocol consisted of high-dose MTX, 1.5 g/m2 of body surface, and high-dose 5-FU, 1.5 g/m2. MTX was administered 1 hr prior to 5-FU. Both drugs were given as a bolus. Twenty-four hours after MTX administration, citrovorum factor rescue was started, 15 mg/m2, q.6h. X 12, orally. Forty-eight hours after MTX administration, serum concentration of the drug was measured by high performance liquid chromatography (HPLC). Fourteen days after MTX was given, ADM, 30 mg/m2, was injected as a bolus. This protocol was repeated every 28 days. Patients eligible for this treatment should have a creatinine clearance of greater than 60 ml/min. The study included 30 patients with metastasizing gastric cancer and performance status between 40% and 70%. The response rate was 63% (19 of 30 patients). Two of 30 patients had complete remissions, which are still maintained. The median survival for responders is not yet evaluable: 68% are living after 17+ mo. The median survival for nonresponders was only 5 mo. The difference in survival curves is significant at a level of p less than 0.05. Cytostatic treatment was well tolerated. Fifty percent of the patients could be treated on an outpatient basis. Total alopecia was observed in only 10% of the patients. Severe leukopenia, thrombocytopenia, and kidney disorders were not observed.
在一项II期试验中，我们试图评估大剂量甲氨蝶呤（MTX）和5-氟尿嘧啶（5-FU）序贯联合阿霉素（ADM）的疗效。在一项前期研究中，我们发现大剂量MTX作为单一药物对胃癌有效。MTX和5-FU序贯联合是因为Cadman等人已证明该联合具有协同作用。治疗方案包括大剂量MTX（1.5 g/m²体表面积）和大剂量5-FU（1.5 g/m²）。MTX在5-FU给药前1小时给予。两种药物均静脉推注。MTX给药24小时后，开始口服亚叶酸解救，剂量为15 mg/m²，每6小时1次，共12次。MTX给药48小时后，通过高效液相色谱法（HPLC）测定药物的血清浓度。MTX给药14天后，静脉推注ADM，剂量为30 mg/m²。该方案每28天重复一次。符合该治疗条件的患者肌酐清除率应大于60 ml/min。该研究纳入了30例转移性胃癌患者，体能状态在40%至70%之间。缓解率为63%（30例患者中有19例）。30例患者中有2例完全缓解，且仍处于缓解状态。缓解者的中位生存期尚未可评估：68%的患者在17个多月后仍存活。未缓解者的中位生存期仅为5个月。生存曲线差异在p<0.05水平具有统计学意义。细胞抑制治疗耐受性良好。50%的患者可在门诊接受治疗。仅10%的患者出现完全脱发。未观察到严重白细胞减少、血小板减少和肾脏疾病。
