Multi-modality megatherapy with [131I]metaiodobenzylguanidine, high dose melphalan and total body irradiation with bone marrow rescue: Feasibility study of a new strategy for advanced neuroblastoma

Gaze, Mark; Wheldon, T. E.; O’Donoghue, Joseph A.; Hilditch, T. E.; McNee, S.G.; Simpson, Elaine M.; Barrett, Ann

doi:10.1016/0959-8049(94)e0036-4

Cited by 65 publications

(46 citation statements)

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“…Incorporation of high-dose 131 I-MIBG treatment into HDCT/auto-SCT might be an option although it also results in late effects. [10][11][12][13][14][15] Matthay et al 15 showed that incorporation of high-dose 131 I-MIBG treatment into HDCT/auto-SCT was feasible and effective in patients with refractory neuroblastoma. However, no studies to date have incorporated high-dose 131 I-MIBG treatment into tandem HDCT/ auto-SCT for treating newly diagnosed high-risk patients.…”

Section: Discussionmentioning

confidence: 99%

“…Tumor status before the first HDCT/auto-SCT was CR for 24 patients, VGPR for 13, PR for 11 and MR for 1. A median of 4.7 Â 10 6 CD34 þ cells/kg (range, 1.4-38.9) was collected during the first leukapheresis round with a median of five leukapheresis events (range, [3][4][5][6][7][8][9][10][11]. One patient underwent a second leukapheresis round to collect at least 2 Â 10 6 CD34 þ cells/kg.…”

Section: Statisticsmentioning

confidence: 99%

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Tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma: Results of SMC NB-2004 study

Sung

Son

Lee

et al. 2012

Bone Marrow Transplant

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, 50 consecutive patients with high-risk neuroblastoma were assigned to receive tandem HDCT (high-dose chemotherapy)/auto-SCT after nine cycles of induction chemotherapy. CEC (carboplatin þ etoposide þ cyclophosphamide) regimen and TM (thiotepa þ melphalan)-TBI regimen (or TM regimen for stage 3 patients) were the first and second HDCT regimens. Local radiotherapy, differentiation therapy with 13-cis-retinoid acid and immunotherapy with interleukin-2 were given after tandem HDCT/auto-SCT. Of the 50 patients, 49 underwent a first HDCT/auto-SCT and 47 underwent a second HDCT/auto-SCT. The tumor relapsed or progressed in 14 patients, secondary malignancy developed in one patient and one patient died from chronic lung disease. Therefore, 34 patients remained event free with a median follow-up of 54.5 months (range, 14-94 months) from diagnosis. The probabilities of 5-year OS and EFS for all 50 patients were 77.0% (95% confidence interval (CI), 63.7-90.3) and 71.4% (95% CI, 58.7-84.1), respectively. However, all patients who remained event free for 43 years after tandem HDCT/auto-SCT experienced late adverse effects. Chemotherapeutic dose-escalation strategy using tandem HDCT/auto-SCT was very encouraging for survival. However, further studies incorporating newer treatment modalities are needed to reduce late adverse effects without jeopardizing the survival rate.

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Section: Discussionmentioning

confidence: 99%

Section: Statisticsmentioning

confidence: 99%

Tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma: Results of SMC NB-2004 study

Sung

Son

Lee

et al. 2012

Bone Marrow Transplant

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“…Clinical experience since 1984 has demonstrated its potential, with an objective response rate of 35% in patients with progressive heavily pretreated disease (Hoefnagel, 1994). Clinical studies are now evaluating the role of ['311]MIBG at an earlier stage in therapy, either as a first line treatment or in combination with other treatment modalities (DeKraker et al, 1995;Gaze et al, 1995;Mastrangelo et al, 1995).Although many patients show beneficial responses to ['311]MIBG treatment, a significant number subsequently relapse from previously undetected tumour sites (Sisson et al, 1989). This suggests that microtumours below the limit of clinical detectability have survived ['311]MIBG therapy.…”

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confidence: 99%

Toxicity to neuroblastoma cells and spheroids of benzylguanidine conjugated to radionuclides with short-range emissions

Cunningham

Mairs²,

Wheldon³

et al. 1998

Br J Cancer

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Summary Radiolabelled meta-iodobenzylguanidine (MIBG) is selectively taken up by tumours of neuroendocrine origin, where its cellular localization is believed to be cytoplasmic. The radiopharmaceutical [1311]MIBG is now widely used in the treatment of neuroblastoma, but other radioconjugates of benzylguanidine have been little studied. We have investigated the cytotoxic efficacy of beta, alpha and Auger electronemitting radioconjugates in treating neuroblastoma cells grown in monolayer or spheroid culture. Using a no-carrier-added synthesis route, we produced 1231-, 1251-, 1311-and 211At-labelled benzylguanidines and compared their in vitro toxicity to the neuroblastoma cell line SK-N-BE(2c) grown in monolayer and spheroid culture. The Auger electron-emitting conjugates ([1231]MIBG and [1251]MIBG) and the alpha-emitting conjugate ([211At]MABG) were highly toxic to monolayers and small spheroids, whereas the beta-emitting conjugate [1311]MIBG was relatively ineffective. The Auger emitters were more effective than expected if the cellular localization of MIBG is cytoplasmic. As dosimetrically predicted however, [211At]MABG was found to be extremely potent in terms of both concentration of radioactivity and number of atoms ml-' administered. In contrast, the Auger electron emitters were ineffective in the treatment of larger spheroids, while the beta emitter showed greater efficacy. These findings suggest that short-range emitters would be well suited to the treatment of circulating tumour cells or small clumps, whereas beta emitters would be superior in the treatment of subclinical metastases or macroscopic tumours. These experimental results provide support for a clinical strategy of combinations ('cocktails') of radioconjugates in targeted radiotherapy.Keywords: meta-iodobenzylguanidine; neuroblastoma; tageted radiotherapy; astatine Meta-iodobenzylguanidine (MIBG) is a structural analogue of the neuroadrenergic blocking drugs bretylium and guanethidine. It is selectively accumulated by an active mechanism in cells of neural crest origin. Radiolabelled MIBG allows the scintigraphic imaging of neural crest tumours (Weiland et al, 1980) and ['311]MIBG is used in the treatment of neuroblastoma and phaeochromocytoma (Hartmann et al, 1987;Mastrangelo, 1987;Schwabe et al, 1987;Voute et al, 1988). Clinical experience since 1984 has demonstrated its potential, with an objective response rate of 35% in patients with progressive heavily pretreated disease (Hoefnagel, 1994). Clinical studies are now evaluating the role of ['311]MIBG at an earlier stage in therapy, either as a first line treatment or in combination with other treatment modalities (DeKraker et al, 1995;Gaze et al, 1995;Mastrangelo et al, 1995).Although many patients show beneficial responses to ['311]MIBG treatment, a significant number subsequently relapse from previously undetected tumour sites (Sisson et al, 1989). This suggests that microtumours below the limit of clinical detectability have survived ['311]MIBG therapy. A possible explanation for the rela...

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“…Although treatment of neuroblastoma with ['311I]MIBG has been shown to be efficacious, improvements in this therapeutic modality are needed and a number of approaches are under active investigation. For example, combination of [311I]MIBG treatment with high-dose chemotherapy and total body irradiation is being pursued (Gaze et al, 1995). For micrometastases, the long-range 3-particles of 'l3I are suboptimal (Sisson et al, 1990; O'Donoghue et al, 1991) and the development of an MIBG analogue labelled with an a-emitter such as 7.2 h half-life 21'At has been advocated (Shapiro et al, 1987;Mairs et al, 1991 (Vaidyanathan and Zalutsky, 1992;Vaidyanathan et al, 1994a).…”

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confidence: 99%

3-[211At]astato-4-fluorobenzylguanidine: a potential therapeutic agent with prolonged retention by neuroblastoma cells

Vaidyanathan

Zhao²,

Larsen³

et al. 1997

Br J Cancer

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Summary An analogue of meta-iodobenzylguanidine (MIBG) in which an aromatic hydrogen was replaced with fluorine has been found to possess many properties similar to those of the parent compound. Moreover, 4-fluoro-3-iodobenzylguanidine (FIBG) (Klingebiel et al, 1989;Garaventa et al, 1991). Although treatment of neuroblastoma with ['311I]MIBG has been shown to be efficacious, improvements in this therapeutic modality are needed and a number of approaches are under active investigation. For example, combination of [311I]MIBG treatment with high-dose chemotherapy and total body irradiation is being pursued (Gaze et al, 1995). For micrometastases, the long-range 3-particles of 'l3I are suboptimal (Sisson et al, 1990; O'Donoghue et al, 1991) and the development of an MIBG analogue labelled with an a-emitter such as 7.2 h half-life 21'At has been advocated (Shapiro et al, 1987;Mairs et al, 1991 (Vaidyanathan and Zalutsky, 1992;Vaidyanathan et al, 1994a). In clonogenic assays with the SK-N-SH human neuroblastoma cell line, the Do value for[21At]MABG was 0.2 kBq mll compared with 384 kBq ml-for no carrier added (n.c.a.) ['311]MIBG, indicating a more than 1000-fold

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Multi-modality megatherapy with [131I]metaiodobenzylguanidine, high dose melphalan and total body irradiation with bone marrow rescue: Feasibility study of a new strategy for advanced neuroblastoma

Cited by 65 publications

References 8 publications

Tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma: Results of SMC NB-2004 study

Tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma: Results of SMC NB-2004 study

Toxicity to neuroblastoma cells and spheroids of benzylguanidine conjugated to radionuclides with short-range emissions

3-[211At]astato-4-fluorobenzylguanidine: a potential therapeutic agent with prolonged retention by neuroblastoma cells

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