Valteau-Couanet Dominique, Michon Jean, Boneu Andrée, Rodary Chantal, Perel Yves, Bergeron Christophe, Rubie Hervé, Coze Carole, Plantaz Dominique, Bernard Frédéric, Chastagner Pascal, Bouzy Jeannine, Hartmann Olivier
Département de Pédiatrie, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France.
J Clin Oncol. 2005 Jan 20;23(3):532-40. doi: 10.1200/JCO.2005.03.054.
To test the metastatic response rate in stage 4 neuroblastoma, using dose-intensive induction chemotherapy in a multi-institutional setting.
From 1998 to 1999, 47 consecutive children were treated according to N7 protocol. Children received cyclophosphamide 140 mg/kg, doxorubicin 75 mg/m(2), and vincristine 0.066 mg/kg (CAV) in cycles 1, 2, 4, and 6, and cisplatinum 200 mg/m(2) and etoposide 600 mg/m(2) (P/VP) in cycles 3, 5, and 7. The International Neuroblastoma Staging system was used with an emphasis on skeletal evaluation by 123-iodine-metaiodobenzylguanidine (MIBG) scintigraphy. A phase II study evaluating the metastasis complete response rate after induction chemotherapy was conducted in patients who had positive metastatic sites on MIBG scans at diagnosis.
Forty-six patients were assessable for toxicity. Hematologic toxicity was the main toxicity observed. Neutropenia was more frequent after CAV than after P/VP (P < .001). A higher rate of thrombocytopenia was observed after P/VP (P = .03). Forty patients with positive MIBG were assessable for metastatic response, and complete regression of metastases was achieved in 17 patients (ie, 43%; 95% CI, 27% to 59%). Of all 47 patients, 21 achieved complete metastatic response.
The N7 induction chemotherapy protocol was feasible in a multicentric setting. The observed metastasis complete response rate was similar to that obtained in our previous studies and significantly lower than that published in a previous series using the same regimen. In our hands, escalating doses of cyclophosphamide and prolonging conventional chemotherapy with the same drugs failed to improve the metastasis complete response rate.
在多机构环境中使用剂量密集诱导化疗,测试4期神经母细胞瘤的转移缓解率。
1998年至1999年,47名连续儿童按照N7方案接受治疗。儿童在第1、2、4和6周期接受环磷酰胺140mg/kg、阿霉素75mg/m²和长春新碱0.066mg/kg(CAV),在第3、5和7周期接受顺铂200mg/m²和依托泊苷600mg/m²(P/VP)。采用国际神经母细胞瘤分期系统,重点通过123碘间碘苄胍(MIBG)闪烁显像进行骨骼评估。对诊断时MIBG扫描有转移阳性部位的患者进行了一项评估诱导化疗后转移完全缓解率的II期研究。
46名患者可评估毒性。血液学毒性是观察到的主要毒性。CAV后中性粒细胞减少比P/VP后更常见(P <.001)。P/VP后观察到更高的血小板减少率(P =.03)。40名MIBG阳性患者可评估转移反应,17名患者实现了转移灶完全消退(即43%;95%CI,27%至59%)。在所有47名患者中,21名实现了完全转移反应。
N7诱导化疗方案在多中心环境中是可行的。观察到的转移完全缓解率与我们之前的研究相似,且显著低于之前使用相同方案发表的系列研究中的缓解率。在我们的研究中,增加环磷酰胺剂量并延长相同药物的传统化疗未能提高转移完全缓解率。