Pinkerton C R, Zucker J M, Hartmann O, Pritchard J, Broadbent V, Morris-Jones P, Breatnach F, Craft A E, Pearson A D, Wallendszus K R
Paediatric Unit, Royal Marsden Hospital, Sutton, Surrey, U.K.
Br J Cancer. 1990 Aug;62(2):319-23. doi: 10.1038/bjc.1990.286.
Fifty-one children, aged from 15 months to 13 years 5 months with metastatic neuroblastoma presenting sequentially at the participating institutions received four 3 to 4 weekly courses of high dose multiagent chemotherapy. High dose cisplatin (200 mg m-2) combined with etoposide (500 mg m-2), HIPE, was alternated with ifosfamide (9 g m-2), vincristine (1.5 mg m-2), and adriamycin (60 mg m-1), IVAd. Disease status was re-evaluated 3 to 4 weeks after the fourth course and the response classified according to the International Neuroblastoma Response Criteria (INRC). The overall response rate in evaluable patients was 55% and response rates by site were: bone marrow 67% (complete response 47%); bone scan 68%; primary tumour 61%, and urinary catecholamine metabolites (VMA/HVA) 95%. Serial 51Cr EDTA renal clearance studies showed a glomerular filtration rate (GFR) decline in 40% of patients but in only seven cases to below 50% of the pretreatment value. There was no instance of renal failure during induction, though two patients developed severe renal failure following 'megatherapy' given to consolidate remission. Serial audiometry showed a significant decline in hearing at frequencies above 2,000 Hz in 37% of children but at or below 2,000 Hz in only 17%. Neutropenia and thrombocytopenia were severe and intravenous antibiotics were required after 30% of courses. Each of two treatment-related deaths occurred during pancytopenia following courses of IVAd. Complete, or greater than 90%, removal of primary site tumour was possible in 70% of cases following this induction regimen and 75% of patients proceeded to elective megatherapy within a median time of 24 weeks after diagnosis. This short intensive induction programme is highly effective at achieving cytoreduction, enabling early surgery and early megatherapy procedures. It is, however, too early to draw firm conclusions about the impact of this approach to treatment on the cure rate.
51名年龄在15个月至13岁5个月之间的转移性神经母细胞瘤患儿先后在参与研究的机构接受了4个疗程、每3至4周一次的大剂量多药化疗。高剂量顺铂（200mg/m²）联合依托泊苷（500mg/m²）（HIPE方案）与异环磷酰胺（9g/m²）、长春新碱（1.5mg/m²）和阿霉素（60mg/m²）（IVAd方案）交替使用。在第四个疗程后3至4周重新评估疾病状态，并根据国际神经母细胞瘤反应标准（INRC）对反应进行分类。可评估患者的总体反应率为55%，各部位的反应率分别为：骨髓67%（完全缓解率47%）；骨扫描68%；原发肿瘤61%，尿儿茶酚胺代谢产物（VMA/HVA）95%。连续的51Cr EDTA肾清除率研究显示，40%的患者肾小球滤过率（GFR）下降，但只有7例降至治疗前值的50%以下。诱导治疗期间无肾衰竭病例，不过有2例患者在巩固缓解的“大剂量治疗”后出现严重肾衰竭。连续听力测定显示，37%的儿童在2000Hz以上频率听力显著下降，而在2000Hz及以下频率听力下降的仅占17%。中性粒细胞减少和血小板减少严重，30%的疗程后需要静脉使用抗生素。IVAd疗程后全血细胞减少期间发生了2例与治疗相关的死亡。按照这种诱导方案，70%的病例有可能完全切除或切除率超过90%的原发部位肿瘤，75%的患者在诊断后中位时间24周内进行了选择性大剂量治疗。这种短期强化诱导方案在实现细胞减灭、使早期手术和早期大剂量治疗成为可能方面非常有效。然而，就这种治疗方法对治愈率的影响得出确凿结论还为时过早。
