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

Overview

Journal J Neurooncol

Publisher Springer

Date 2004 Mar 16

PMID 15015787

Citations 19

Authors

N G Rainov

V Heidecke

Affiliations

Soon will be listed here.

Abstract

Intratumoral infusion of a recombinant targeted toxin (NBI-3001) consisting of the receptor binding domain of human interleukin 4 (IL-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 microg/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.

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References

Rand R, Kreitman R, Patronas N, Varricchio F, Pastan I, Puri R . Intratumoral administration of recombinant circularly permuted interleukin-4-Pseudomonas exotoxin in patients with high-grade glioma. Clin Cancer Res. 2000; 6(6):2157-65. View

Laske D, Ilercil O, Akbasak A, Youle R, Oldfield E . Efficacy of direct intratumoral therapy with targeted protein toxins for solid human gliomas in nude mice. J Neurosurg. 1994; 80(3):520-6. DOI: 10.3171/jns.1994.80.3.0520. View

Di Massimo A, Di Loreto M, Pacilli A, Raucci G, DAlatri L, Mele A . Immunoconjugates made of an anti-EGF receptor monoclonal antibody and type 1 ribosome-inactivating proteins from Saponaria ocymoides or Vaccaria pyramidata. Br J Cancer. 1997; 75(6):822-8. PMC: 2063398. DOI: 10.1038/bjc.1997.147. View

Husain S, Joshi B, Puri R . Interleukin-13 receptor as a unique target for anti-glioblastoma therapy. Int J Cancer. 2001; 92(2):168-75. DOI: 10.1002/1097-0215(200102)9999:9999<::aid-ijc1182>3.0.co;2-n. View

Puri R, Leland P, Kreitman R, 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. 1994; 58(4):574-81. DOI: 10.1002/ijc.2910580421. View

Laske D, Youle R, Oldfield E . Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors. Nat Med. 1997; 3(12):1362-8. DOI: 10.1038/nm1297-1362. View

Burger P, Green S . Patient age, histologic features, and length of survival in patients with glioblastoma multiforme. Cancer. 1987; 59(9):1617-25. DOI: 10.1002/1097-0142(19870501)59:9<1617::aid-cncr2820590916>3.0.co;2-x. View

Puri R, Hoon D, Leland P, Snoy P, Rand R, Pastan I . Preclinical development of a recombinant toxin containing circularly permuted interleukin 4 and truncated Pseudomonas exotoxin for therapy of malignant astrocytoma. Cancer Res. 1996; 56(24):5631-7. View

Frankel A, Kreitman R, Sausville E . Targeted toxins. Clin Cancer Res. 2000; 6(2):326-34. View

10.

Weber F, Asher A, Bucholz R, Berger M, Prados M, Chang S . Safety, tolerability, and tumor response of IL4-Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma. J Neurooncol. 2003; 64(1-2):125-37. DOI: 10.1007/BF02700027. View

11.

Husain S, Behari N, Kreitman R, Pastan I, Puri R . Complete regression of established human glioblastoma tumor xenograft by interleukin-4 toxin therapy. Cancer Res. 1998; 58(16):3649-53. View

12.

Brem H, Piantadosi S, Burger P, Walker M, SELKER R, Vick N . 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. 1995; 345(8956):1008-12. DOI: 10.1016/s0140-6736(95)90755-6. View