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British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Feb;84(4):460–464. doi: 10.1054/bjoc.2000.1645

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

S Mastrangelo 1, A Tornesello 1, L Diociaiuti 1, A Pession 3, A Prete 3, V Rufini 2, L Troncone 3, R Mastrangelo 1
PMCID: PMC2363758  PMID: 11207038

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/m2i.v. per day infused over 2 h, for 4 consecutive days; on day 4 Cy 2 g/m2i.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/m2i.v. per day was administered as a 24 h infusion on days 1–3; Vincristine 1.5 mg/m2i.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

Keywords: neuroblastoma, combined therapy, 131-I-metaiodobenzylguanidine

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Selected References

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  1. Armour A., Cunningham S. H., Gaze M. N., Wheldon T. E., Mairs R. J. The effect of cisplatin pretreatment on the accumulation of MIBG by neuroblastoma cells in vitro. Br J Cancer. 1997;75(4):470–476. doi: 10.1038/bjc.1997.82. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beierwaltes W. H. Treatment of neuroblastoma with 131I-MIBG: dosimetric problems and perspectives. Med Pediatr Oncol. 1987;15(4):188–191. doi: 10.1002/mpo.2950150409. [DOI] [PubMed] [Google Scholar]
  3. Brodeur G. M., Pritchard J., Berthold F., Carlsen N. L., Castel V., Castelberry R. P., De Bernardi B., Evans A. E., Favrot M., Hedborg F. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 1993 Aug;11(8):1466–1477. doi: 10.1200/JCO.1993.11.8.1466. [DOI] [PubMed] [Google Scholar]
  4. De Kraker J., Hoefnagel C. A., Caron H., Valdés Olmos R. A., Zsiros J., Heij H. A., Voûte P. A. First line targeted radiotherapy, a new concept in the treatment of advanced stage neuroblastoma. Eur J Cancer. 1995;31A(4):600–602. doi: 10.1016/0959-8049(95)00063-o. [DOI] [PubMed] [Google Scholar]
  5. Frappaz D., Michon J., Hartmann O., Bouffet E., Lejars O., Rubie H., Gentet J. C., Chastagner P., Sariban E., Brugiere L. Etoposide and carboplatin in neuroblastoma: a French Society of Pediatric Oncology phase II study. J Clin Oncol. 1992 Oct;10(10):1592–1601. doi: 10.1200/JCO.1992.10.10.1592. [DOI] [PubMed] [Google Scholar]
  6. Geatti O., Shapiro B., Sisson J. C., Hutchinson R. J., Mallette S., Eyre P., Beierwaltes W. H. Iodine-131 metaiodobenzylguanidine scintigraphy for the location of neuroblastoma: preliminary experience in ten cases. J Nucl Med. 1985 Jul;26(7):736–742. [PubMed] [Google Scholar]
  7. Lashford L. S., Lewis I. J., Fielding S. L., Flower M. A., Meller S., Kemshead J. T., Ackery D. Phase I/II study of iodine 131 metaiodobenzylguanidine in chemoresistant neuroblastoma: a United Kingdom Children's Cancer Study Group investigation. J Clin Oncol. 1992 Dec;10(12):1889–1896. doi: 10.1200/JCO.1992.10.12.1889. [DOI] [PubMed] [Google Scholar]
  8. Mastrangelo R., Lasorella A., Iavarone A., Rufini V., Troncone L., Danza F., Riccardi R. Critical observations on neuroblastoma treatment with 131-I-metaiodobenzylguanidine at diagnosis. Med Pediatr Oncol. 1993;21(6):411–415. doi: 10.1002/mpo.2950210604. [DOI] [PubMed] [Google Scholar]
  9. Mastrangelo R. The treatment of neuroblastoma with 131I-MIBG. Med Pediatr Oncol. 1987;15(4):157–158. doi: 10.1002/mpo.2950150403. [DOI] [PubMed] [Google Scholar]
  10. Mastrangelo R., Tornesello A., Lasorella A., Iavarone A., Mastrangelo S., Riccardi R., Diociaiuti L., Rufini V., Pession A., Troncone L. Optimal use of the 131-I-metaiodobenzylguanidine and cisplatin combination in advanced neuroblastoma. J Neurooncol. 1997 Jan;31(1-2):153–158. doi: 10.1023/a:1005770405844. [DOI] [PubMed] [Google Scholar]
  11. Mastrangelo R., Tornesello A., Riccardi R., Lasorella A., Mastrangelo S., Mancini A., Rufini V., Troncone L. A new approach in the treatment of stage IV neuroblastoma using a combination of [131I]meta-iodobenzylguanidine (MIBG) and cisplatin. Eur J Cancer. 1995;31A(4):606–611. doi: 10.1016/0959-8049(95)00048-n. [DOI] [PubMed] [Google Scholar]
  12. Mastrangelo R., Troncone L., Lasorella A., Riccardi R., Montemaggi P., Rufini V. 131I-metaiodobenzylguanidine in the treatment of neuroblastoma at diagnosis. Am J Pediatr Hematol Oncol. 1989 Spring;11(1):28–31. doi: 10.1097/00043426-198921000-00007. [DOI] [PubMed] [Google Scholar]
  13. Mastrangelo R., Voûte P. A. Session on the treatment of neuroblastoma with radioiodinated metaiodobenzylguanidine. Chairmen's report. J Nucl Biol Med. 1991 Oct-Dec;35(4):260–262. [PubMed] [Google Scholar]
  14. Matthay K. K., DeSantes K., Hasegawa B., Huberty J., Hattner R. S., Ablin A., Reynolds C. P., Seeger R. C., Weinberg V. K., Price D. Phase I dose escalation of 131I-metaiodobenzylguanidine with autologous bone marrow support in refractory neuroblastoma. J Clin Oncol. 1998 Jan;16(1):229–236. doi: 10.1200/JCO.1998.16.1.229. [DOI] [PubMed] [Google Scholar]
  15. Matthay K. K., Villablanca J. G., Seeger R. C., Stram D. O., Harris R. E., Ramsay N. K., Swift P., Shimada H., Black C. T., Brodeur G. M. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children's Cancer Group. N Engl J Med. 1999 Oct 14;341(16):1165–1173. doi: 10.1056/NEJM199910143411601. [DOI] [PubMed] [Google Scholar]
  16. Millar J. L., Blackett N. M., Hudspith B. N. Enhanced post-irradiation recovery of the haemopoietic system in animals pretreated with a variety of cytotoxic agents. Cell Tissue Kinet. 1978 Sep;11(5):543–553. doi: 10.1111/j.1365-2184.1978.tb00826.x. [DOI] [PubMed] [Google Scholar]
  17. Millar J. L., Hudspith B. N. Sparing effect of cyclophosphamide (NSC-26271) pretreatment on animals lethally treated with gamma-irradiation. Cancer Treat Rep. 1976 Apr;60(4):409–414. [PubMed] [Google Scholar]
  18. Philip T., Ghalie R., Pinkerton R., Zucker J. M., Bernard J. L., Leverger G., Hartmann O. A phase II study of high-dose cisplatin and VP-16 in neuroblastoma: a report from the Société Française d'Oncologie Pédiatrique. J Clin Oncol. 1987 Jun;5(6):941–950. doi: 10.1200/JCO.1987.5.6.941. [DOI] [PubMed] [Google Scholar]
  19. 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. Short duration, high dose, alternating chemotherapy in metastatic neuroblastoma. (ENSG 3C induction regimen). The European Neuroblastoma Study Group. Br J Cancer. 1990 Aug;62(2):319–323. doi: 10.1038/bjc.1990.286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Simone J. V. The treatment of neuroblastoma. J Clin Oncol. 1984 Jul;2(7):717–718. doi: 10.1200/JCO.1984.2.7.717. [DOI] [PubMed] [Google Scholar]
  21. Wieland D. M., Wu J., Brown L. E., Mangner T. J., Swanson D. P., Beierwaltes W. H. Radiolabeled adrenergi neuron-blocking agents: adrenomedullary imaging with [131I]iodobenzylguanidine. J Nucl Med. 1980 Apr;21(4):349–353. [PubMed] [Google Scholar]
  22. Yan R., Peters L. J., Travis E. L. Cyclophosphamide 24 hours before or after total body irradiation: effects on lung and bone marrow. Radiother Oncol. 1991 Jul;21(3):149–156. doi: 10.1016/0167-8140(91)90031-b. [DOI] [PubMed] [Google Scholar]

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