High dose administration of anticancer drugs was discussed putting an emphasis on methotrexate and cytosine arabinoside. High dose methotrexate in combination with leucovorin rescue was effective on various kinds of cancer which had become resistant to conventional doses of anti-cancer drugs. The administration of high-dose methotrexate, however, should be performed with meticulous precautions to prevent serious side effects. Side effects included gastrointestinal mucositis, hepatic dysfunction, nausea and vomiting. Central nervous system manifestations were sometimes observed. High-dose cytosine arabinoside of 3 g/m2 per 12 hours X 12 was given by 2-hours infusion to patients with acute leukemia who had become resistant to conventional combination chemotherapy, or to relapsed patients. This regimen in combination with L-asparaginase or anthracyclines resulted in a fairly high remission rate among those intractable cases. High-dose cytosine arabinoside in combination with anthracyclines has recently been tried on patients with acute leukemia as an initial treatment for remission induction and consolidation. In this case, no intensification treatment was performed to maintain remission. Patients treated with this regimen as an initial medication showed a high remission induction rate and long remission duration. Forty percent of the patients were still alive after 3 years.
讨论了抗癌药物的高剂量给药,重点是甲氨蝶呤和阿糖胞苷。高剂量甲氨蝶呤联合亚叶酸钙解救对多种已对常规剂量抗癌药物产生耐药性的癌症有效。然而,高剂量甲氨蝶呤的给药应采取细致的预防措施以防止严重的副作用。副作用包括胃肠道粘膜炎、肝功能障碍、恶心和呕吐。有时会观察到中枢神经系统表现。对于对常规联合化疗产生耐药性的急性白血病患者或复发患者,每12小时给予3 g/m²的高剂量阿糖胞苷,共12次,通过2小时输注给药。该方案与L-天冬酰胺酶或蒽环类药物联合使用,在这些难治性病例中产生了相当高的缓解率。高剂量阿糖胞苷与蒽环类药物联合使用最近已在急性白血病患者中作为诱导缓解和巩固的初始治疗方法进行尝试。在这种情况下,未进行强化治疗以维持缓解。以该方案作为初始用药治疗的患者显示出高缓解诱导率和长缓解持续时间。40%的患者在3年后仍然存活。