Coze C, Hartmann O, Michon J, Frappaz D, Dusol F, Rubie H, Plouvier E, Leverger G, Bordigoni P, Béhar C, Beck D, Mechinaud F, Bergeron C, Plantaz D, Otten J, Zucker J M, Philip T, Bernard J L
Pediatric Oncology Department of Hôpital d'Enfants de la Timone, Marseille, France.
J Clin Oncol. 1997 Dec;15(12):3433-40. doi: 10.1200/JCO.1997.15.12.3433.
NB87 was designed to test the efficacy of a short, non cross-resistant, induction protocol for unselected patients over 1 year of age with stage 4 neuroblastoma. A secondary objective was to compare in a randomized study the toxicity of two modalities of cisplatin administration.
A total of 183 patients received two cycles of alternating sequences: cyclophosphamide 300 mg/m2/d on days 1 to 5, vincristine 1.5 mg/m2/d on days 1 and 5, and doxorubicin 60 mg/m2/d on day 5 (CADO); and cisplatin 40 mg/m2/d and etoposide 100 mg/m2/d on days 1 to 5 (CVP), followed by surgery of the primary tumor (126 patients). Ninety-one were randomized to receive cisplatin either as bolus (BO; n = 48) or continuous infusion (CI; n = 43). International Neuroblastoma Staging System (INSS) and Response Criteria (INRC) were used with emphasis on skeletal evaluation by meta-iodobenzylguanidine (MIBG).
Hematotoxicity was predominant, with a higher incidence of neutropenia (P = .01) for CADO and of thrombocytopenia for CVP (P < .001). Severe infections, as well as nonhematologic toxicities, occurred more often after the first sequence. Gastrointestinal complications were predominant during both courses of CVP. The toxic death rate, including surgery, was 3%. Complete remissions (CRs) were less frequent on MIBG (45%) compared with marrow (66%) or other metastases (61%). Combining all metastatic sites resulted in a 39% CR rate. After surgery, the final CR rate was 42%. Nephrotoxicity was minimal in both arms (92% normal clearance for CI v 82% for BO). Hearing loss greater than 40 dB at 6,000 to 8,000 Hz was reported equally in both arms (n = 6 for CI v n = 5 for BO).
Intensified chemotherapy using CADO/CVP increases CR rates despite a shorter induction duration. However, the rate of MIBG normalization remains unsatisfactory and could be raised through the dose-intensive use of agents such as cyclophosphamide.
NB87旨在测试一种简短、无交叉耐药性的诱导方案对1岁以上4期神经母细胞瘤未选择患者的疗效。次要目标是在一项随机研究中比较顺铂两种给药方式的毒性。
总共183例患者接受两个周期的交替序列治疗：第1至5天环磷酰胺300mg/m²/天、第1天和第5天长春新碱1.5mg/m²/天、第5天阿霉素60mg/m²/天（CADO）；以及第1至5天顺铂40mg/m²/天和依托泊苷100mg/m²/天（CVP），随后对原发肿瘤进行手术（126例患者）。91例患者被随机分组，分别接受大剂量推注顺铂（BO；n = 48）或持续输注顺铂（CI；n = 43）。采用国际神经母细胞瘤分期系统（INSS）和反应标准（INRC），重点通过间碘苄胍（MIBG）进行骨骼评估。
血液毒性为主，CADO组中性粒细胞减少发生率较高（P = 0.01），CVP组血小板减少发生率较高（P < 0.001）。严重感染以及非血液学毒性在第一个序列后更常发生。CVP两个疗程中胃肠道并发症均为主。包括手术在内的毒性死亡率为3%。与骨髓（66%）或其他转移灶（61%）相比，MIBG完全缓解（CR）率较低（45%）。综合所有转移部位，CR率为39%。手术后，最终CR率为42%。两组肾毒性均最小（CI组正常清除率为92%，BO组为82%）。两组在6000至8000Hz时听力损失大于40dB的报告发生率相同（CI组n = 6，BO组n = 5）。
尽管诱导期较短，但使用CADO/CVP强化化疗可提高CR率。然而，MIBG正常化率仍不令人满意，可通过大剂量使用环磷酰胺等药物提高。
