Forastiere A A, Natale R B, Wheeler R R
Cancer. 1986 Dec 15;58(12):2585-8. doi: 10.1002/1097-0142(19861215)58:12<2585::aid-cncr2820581205>3.0.co;2-2.
Methylglyoxal bis (guanylhydrazone) (MGBG) is an inhibitor of polyamine synthesis. In vitro studies demonstrate the accumulation of some tumor cells in S and G2 phases of the cell cycle. Nineteen patients with advanced head and neck cancer were entered in a Phase II trial of MGBG. MGBG, 500 mg/M2, was administered as a brief intravenous infusion weekly for 4 weeks, then every 2 weeks. Dose modifications were based on cumulative toxicity after 2 weekly treatments. All but three patients had prior exposure to chemotherapy for disease recurrence. Of 17 patients evaluable for response and toxicity, one brief partial response was observed. The most common toxicities were mild to moderate nausea, vomiting, diarrhea, and stomatitis. Myelosuppression occurred in three patients. Dose modifications were required in four patients; a maximum dose of 700 mg/M2 was tolerated. The results of four other Phase II single and combination chemotherapy trials of MGBG in head and neck cancer are reviewed. The single agent response rate in 59 patients was 22% (range, 6%-41%). The poor response rate observed in this trial was similar to that in other trials in which a heavily pretreated group of patients was evaluated. It is concluded that single agent MGBG is not a useful drug in heavily pretreated recurrent disease patients. However, because of its biochemical effects, further testing in combination with cycle specific agents and in larger numbers of patients with minimal prior treatment may be warranted.
甲基乙二醛双（脒腙）（MGBG）是一种多胺合成抑制剂。体外研究表明，某些肿瘤细胞在细胞周期的S期和G2期会积聚。19例晚期头颈癌患者进入了MGBG的II期试验。MGBG剂量为500mg/M²，通过短暂静脉输注给药，每周1次，共4周，之后每2周1次。剂量调整基于2周治疗后的累积毒性。除3例患者外，其他患者均曾因疾病复发接受过化疗。在可评估疗效和毒性的17例患者中，观察到1例短暂部分缓解。最常见的毒性反应为轻至中度恶心、呕吐、腹泻和口腔炎。3例患者出现骨髓抑制。4例患者需要调整剂量；最大耐受剂量为700mg/M²。本文还回顾了其他4项MGBG用于头颈癌的II期单药及联合化疗试验结果。59例患者的单药有效率为22%（范围6%-41%）。本试验中观察到的低有效率与其他评估高度预处理患者组的试验相似。得出的结论是，单药MGBG对高度预处理的复发疾病患者并非有效药物。然而，由于其生化作用，与细胞周期特异性药物联合使用并在既往治疗较少的大量患者中进行进一步试验可能是有必要的。
