Treatment of advanced neuroblastoma: feasibility and therapeutic potential of a novel approach combining 131-I-MIBG and multiple drug chemotherapy

Abstract

Biological and clinical observations suggest that initial marked reduction of resistant clones may be critical in any attempt to improve long-term results in advanced neuroblastoma (NB). The aim of this pilot study is to determine short-term toxicity and efficacy of a new therapeutic model based on the simultaneous use of multiple drug chemotherapy and specific irradiation using 131-I-MIBG. The study population consisted of 21 patients, from 1 to 8 years of age with good 131-I-MIBG uptake. 16 extensively pre-treated patients with refractory or relapsed disease were divided into 2 groups. In Group 1 (9 patients) the basic chemotherapy regimen consisted in cisplatin at the dose of 20 mg/m 2 i.v. per day infused over 2 h, for 4 consecutive days; on day 4 Cy 2 g/m 2 i.v. was administered over 2 h followed by Mesna. Group 2 (7 patients) was treated with basic chemotherapeutic regimen plus VP16 and Vincristine. VP16 at the dose of 50 mg/m 2 i.v. per day was administered as a 24 h infusion on days 1–3; Vincristine 1.5 mg/m 2 i.v. was administered on days 1 and 6. On day 10 a single dose of 131-I-MIBG (200 mCi) with a high specific activity (>1.1 GBq/mg) was administered to both Groups by i.v. infusion over 4–6 hours. A further 5 patients were treated at diagnosis: 2 with the same regimen as Group 1 and 3 with the same as Group 2. The severity of toxicity was graded according to World Health Organization (WHO) criteria. Assessment of tumour response was monitored 4–6 weeks after the beginning of combined therapy (CO-TH). Response was defined according to INSS (International Neuroblastoma Staging System) criteria. No extra-medullary toxicity was observed in any patient. Haematological toxicity was the only toxicity observed and seemed mainly related to chemotherapy. Myelosuppression was mild in the 5 patients treated at diagnosis. No serious infections or significant bleeding problems were observed. In the 16 resistant patients, 12 PR, 1 mixed response and 3 SD were obtained. In the 5 patients treated at diagnosis 2 PR, 1 CR and 2 VGPR were observed. No alteration in 131-I-MIBG uptake was observed after the chemotherapy preceding radio-metabolic treatment. The therapeutic results of this pilot regimen of CO-TH resulted in a high percentage of major response after only a single course in both resistant patients and patients treated at diagnosis. Because of the minimal toxicity observed in patients studied at diagnosis so far, there is room for gradual intensification of the treatment. It is to be hoped that this suggested novel approach may represent an important route of investigation to improve final outcome in patients with advanced NB. © 2001 Cancer Research Campaign http://www.bjcancer.com

28 years of high-dose therapy and SCT for neuroblastoma in Europe: lessons from more than 4000 procedures

“…38 Preliminary results of the association of melphalan with TBI and MIBG demonstrate the feasibility of such a regimen. [39][40][41] High doses of MIBG alone or in combination with topotecan 42 or other radiosensitizing agents such as CDDP 43,44 followed by PBSCR have been piloted with early promising results in poor responding or relapse patients. 9.…”

Norepinephrine Transporter as a Target for Imaging and Therapy

“…MIBG therapy has usually been given to patients at relapse: both high-dose and multiple-dose strategies have been used (Fig. 3), and combined treatment with chemotherapy or biologic therapy has been studied (Table 1) (36,(72)(73)(74)(75)(76)(77)(78)(79)(80).…”

Target Therapy in Neuroblastoma

“…• Italian investigators treated 16 children with refractory or relapsed neuroblastoma using 131 I-MIBG combined with cisplatin and cyclophosphamide with or without etoposide and vincristine and obtained 12 PRs [35].…”