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Journal of Neuro-Oncology

, Volume 66, Issue 1–2, pp 197–201 | Cite as

Long Term Survival in a Patient with Recurrent Malignantc Glioma Treated with Intratumoral Infusion of an IL4-Targeted Toxin (NBI-3001)

  • N.G. Rainov
  • V. Heidecke
Article

Abstract

Intratumoral infusion of a recombinant targeted toxin (NBI-3001) consisting of the receptor binding domain of human interleukin 4 (1L-4) and Pseudomonas aeruginosa exotoxin A is an investigational treatment for malignant brain tumors. This 27-year-old male patient presented with a recurrent malignant glioma WHO grade IV after surgery and adjuvant radiation and chemotherapy. The recurrence was treated with intratumoral infusion of NBI-3001 at a dose of 9 μg/ml in 66 ml of infusate. Treatment resulted in long-term survival for 3 years after toxin infusion with a durable tumor response. There were some permanent neurological side effects resulting from toxin infusion. The patient eventually died after a late local recurrence of the known brain tumor.

Such clinical evolution of a malignant glioma after a single round of immunotoxin infusion is rather unusual. The late local recurrence may suggest that repeated courses rather than a single infusion of intratumoral toxin are possibly needed for successful long term tumor control.

astrocytoma glioblastoma immunotoxin interleukin-4 receptor NBI-3001 

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References

  1. 1.
    Frankel AE, Kreitman RJ, Sausville EA: Targeted toxins. Clin Cancer Res 6: 326-334, 2000Google Scholar
  2. 2.
    Husain SR, Behari N, Kreitman RJ, Pastan I, Puri RK: Complete regression of established human glioblastoma tumor xenograft by interleukin-4 toxin therapy. Cancer Res 58: 3649-3653, 1998Google Scholar
  3. 3.
    Husain SR, Joshi BH, Puri RK: Interleukin-13 receptor as a unique target for anti-glioblastoma therapy. Int J Cancer 92: 168-175, 2001Google Scholar
  4. 4.
    Puri RK, Hoon DS, Leland P, Snoy P, Rand RW, Pastan I, Kreitman RJ: Preclinical development of a recombinant toxin containing circularly permuted interleukin 4 and truncated Pseudomonas exotoxin for therapy of malignant astrocytoma. Cancer Res 56: 5631-5637, 1996Google Scholar
  5. 5.
    Laske DW, Youle RJ, Oldfield EH: Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors. Nat Med 3: 1362-1368, 1997Google Scholar
  6. 6.
    Di Massimo AM, Di Loreto M, Pacilli A, Raucci G, D'Alatri L, Mele A, Bolognesi A, Polito L, Stirpe F, De Santis R: Immunoconjugates made of an anti-EGF receptor monoclonal antibody and type 1 ribosome-inactivating proteins from Saponaria ocymoides or Vaccaria pyramidata. Br J Cancer 75: 822-828, 1997Google Scholar
  7. 7.
    Laske DW, Ilercil O, Akbasak A, Youle RJ, Oldfield EH: Efficacy of direct intratumoral therapy with targeted protein toxins for solid human gliomas in nude mice. J Neurosurg 80: 520-526, 1994Google Scholar
  8. 8.
    Puri RK, Leland P, Kreitman RJ, Pastan I: Human neurological cancer cells express interleukin-4 (IL-4) receptors which are targets for the toxic effects of IL4-Pseudomonas exotoxin chimeric protein. Int J Cancer 58: 574-581, 1994Google Scholar
  9. 9.
    Rand RW, Kreitman RJ, Patronas N, Varricchio F, Pastan I, Puri RK: Intratumoral administration of recombinant circularly permuted interleukin-4-Pseudomonas exotoxin in patients with high-grade glioma. Clin Cancer Res 6: 2157-2165, 2000Google Scholar
  10. 10.
    Weber F, Asher A, Bucholz R, Berger M, Prados M, Chang S, Bruce J, Hall W, Rainov NG, Westphal M, Warnick RE, Rand RW, Floeth F, Rommel F, Pan H, Hingorani VN, Puri RK: Safety, tolerability, and tumor response of IL4-Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma. J Neuro-Oncol 64: 125-137, 2003Google Scholar
  11. 11.
    Burger PC, Green SB: Patient age, histological features, and length of survival in patients with glioblastoma multiforme. Cancer 59: 1617-1625, 1987Google Scholar
  12. 12.
    Brem H, Piantadosi S, Burger PC, Walker M, Selker R, Vick NA, Black K, Sisti M, Brem S, Mohr G: Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The polymer-brain tumor treatment group. Lancet 345: 1008-1012, 1995Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • N.G. Rainov
    • 1
    • 2
  • V. Heidecke
    • 3
  1. 1.Department of Neurological ScienceUniversity of LiverpoolUK
  2. 2.The Walton Centre for Neurology and Neurosurgery NHS TrustLiverpoolUK
  3. 3.Department of NeurosurgeryMartin-Luther UniversityHalleGermany

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