Impact of repeated cycles of EGF bispecific angiotoxin (eBAT) administered at a reduced interval from doxorubicin chemotherapy in dogs with splenic haemangiosarcoma

Antonella Borgatti, Ann Fieberg, Amber L. Winter, Kathleen Stuebner, Elizabeth Taras, Deborah Todhunter, Alison Masyr, Aaron Rendhal, Daniel A. Vallera, Joseph S. Koopmeiners, Jaime F. Modiano

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

We previously reported that eBAT, an EGF-targeted angiotoxin, was safe and it improved the overall survival for dogs with splenic haemangiosarcoma when added to the standard of care in a single cycle of three administrations in the minimal residual disease setting. Our objective for the SRCBST-2 trial was to assess whether increased dosing through multiple cycles of eBAT would be well tolerated and would further enhance the benefits of eBAT. Eligibility was expanded to dogs with stage 3 haemangiosarcoma, provided that gross lesions could be surgically excised. The interval between eBAT and the start of chemotherapy was reduced, and the experimental therapy was expanded to three cycles, each administered at the biologically active dose (50 μg/kg) on a Monday/Wednesday/Friday schedule following splenectomy, and scheduled 1 week prior to the first, second and fifth doxorubicin chemotherapy. Twenty-five dogs were enrolled; six experienced acute hypotension with two requiring hospitalization. Self-limiting elevation of ALT was observed in one dog. A statistically significant survival benefit was not seen in this study in eBAT-treated dogs compared with a Contemporary comparison group of dogs with stages 1-3 haemangiosarcoma treated with standard of care alone. Our results indicate that repeated dosing cycles of eBAT starting 1 week prior to doxorubicin chemotherapy led to greater toxicity and reduced efficacy compared with a single cycle given between surgery and a delayed start of chemotherapy. Further work is needed to understand the precise mechanisms of action of eBAT in order to optimize its clinical benefits in the treatment of canine haemangiosarcoma and other tumours. IACUC Protocols 1110A06186 and 1507-32804A.

Original languageEnglish (US)
Pages (from-to)664-674
Number of pages11
JournalVeterinary and Comparative Oncology
Volume18
Issue number4
DOIs
StatePublished - Nov 2020

Bibliographical note

Funding Information:
We thank the oncology clinicians and staff of the University of Minnesota Veterinary Medical Center for assistance with management of dogs participating in the study, and importantly, clients who allowed their pets to enrol in the study, and the dogs who made the study possible. This work was supported by grant K01OD017242 (A. B.) from the Office of The Director, National Institutes of Health, grant AB15MN‐002 from the National Canine Cancer Foundation (A. B.), a grant from the Masonic Cancer Center, University of Minnesota Sarcoma Translational Working Group (J. F. M., D. A. V., A. B., J. S. K.), Cancer Center Support Grant, P30 CA077598 (Masonic Cancer Center, University of Minnesota), grant 1889‐G from the AKC Canine Health Foundation (J. F. M.), the US Public Health Service Grant R01 CA36725 awarded by the NCI and the NIAID, DHHS (D. A. V.), the Randy Shaver Cancer Research and Community Foundation (D. A. V.), Hyundai Scholar Senior Research Award, Hyundai Hope on Wheels (D. A. V.), a CETI Translational Award from the University of Minnesota Masonic Cancer Center (D. A. V.), and a grant from GREYlong (J. F. M.). The authors gratefully acknowledge generous support from the Angiosarcoma Awareness Foundation and donations to the Animal Cancer Care and Research Program of the University of Minnesota that helped support this project. J. F. M. is supported in part by the Alvin S. and June Perlman Chair in Animal Oncology at the University of Minnesota.

Funding Information:
We thank the oncology clinicians and staff of the University of Minnesota Veterinary Medical Center for assistance with management of dogs participating in the study, and importantly, clients who allowed their pets to enrol in the study, and the dogs who made the study possible. This work was supported by grant K01OD017242 (A. B.) from the Office of The Director, National Institutes of Health, grant AB15MN-002 from the National Canine Cancer Foundation (A. B.), a grant from the Masonic Cancer Center, University of Minnesota Sarcoma Translational Working Group (J. F. M., D. A. V., A. B., J. S. K.), Cancer Center Support Grant, P30 CA077598 (Masonic Cancer Center, University of Minnesota), grant 1889-G from the AKC Canine Health Foundation (J. F. M.), the US Public Health Service Grant R01 CA36725 awarded by the NCI and the NIAID, DHHS (D. A. V.), the Randy Shaver Cancer Research and Community Foundation (D. A. V.), Hyundai Scholar Senior Research Award, Hyundai Hope on Wheels (D. A. V.), a CETI Translational Award from the University of Minnesota Masonic Cancer Center (D. A. V.), and a grant from GREYlong (J. F. M.). The authors gratefully acknowledge generous support from the Angiosarcoma Awareness Foundation and donations to the Animal Cancer Care and Research Program of the University of Minnesota that helped support this project. J. F. M. is supported in part by the Alvin S. and June Perlman Chair in Animal Oncology at the University of Minnesota.

Funding Information:
American Kennel Club Canine Health Foundation, Grant/Award Number: 1889‐G; Angiosarcoma Awareness Foundation; Animal Cancer Care and Research Program, UMN; GREYlong; Hyundai Hope On Wheels, Grant/Award Number: Hyundai Scholar Senior Research Award; Masonic Cancer Center UMN, Grant/Award Number: P30 CA077598; Masonic Cancer Center, UMN, Grant/Award Number: CETI Translational Award; Masonic Cancer Center, University of Minnesota Sarcoma Translational Working Group; National Canine Cancer Foundation, Grant/Award Number: AB15MN‐002 f; NCI NIAID, Grant/Award Number: R01 CA36725; National Institute of Health, Grant/Award Number: K01OD017242; Randy Shaver Cancer Research and Community Foundation Funding information

Publisher Copyright:
© 2020 John Wiley & Sons Ltd

Keywords

  • canine
  • epidermal growth factor receptor
  • haemangiosarcoma
  • sarcoma
  • targeted toxin
  • urokinase plasminogen activator receptor

PubMed: MeSH publication types

  • Journal Article
  • Comparative Study

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