Intrathecal substance P-saporin in the dog: efficacy in bone cancer pain

Abstract

Background: Substance P-saporin (SP-SAP), a chemical conjugate of substance P and a recombinant version of the ribosome-inactivating protein, saporin, when administered intrathecally, acts as a targeted neurotoxin producing selective destruction of superficial neurokinin-1 receptor-bearing cells in the spinal dorsal horn. The goal of this study was to provide proof-of-concept data that a single intrathecal injection of SP-SAP could safely provide effective pain relief in spontaneous bone cancer pain in companion (pet) dogs.

Methods: In a single-blind, controlled study, 70 companion dogs with bone cancer pain were randomized to standard-of-care analgesic therapy alone (control, n=35) or intrathecal SP-SAP (20-60 µg) in addition to standard-of-care analgesic therapy (n=35). Activity, pain scores, and videography data were collected at baseline, 2 weeks postrandomization, and then monthly until death.

Results: Although the efficacy results at the 2-week postrandomization point were equivocal, the outcomes evaluated beyond 2 weeks revealed a positive effect of SP-SAP on chronic pain management. Significantly, more dogs in the control group (74%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization than dogs that were treated with SP-SAP (24%; P<0.001); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with SP-SAP (P<0.01).

Conclusion: Intrathecal administration of SP-SAP in dogs with bone cancer produces a time-dependent antinociceptive effect with no evidence of development of deafferentation pain syndrome which can be seen with neurolytic therapies.

Figure 1

Dogs were randomized to standard of care analgesics alone or standard of care analgesics in addition to intrathecal substance-p saporin (SAP) injection. Owners were blinded to treatment group. Data was collected at baseline, two weeks after randomization, and monthly thereafter until the dog's death. Following the two week postrandomization assessment, unblinding occurred when the owner requested additional intervention for chronic pain management. At that point, dogs that had already received SAP had adjustments made to the standard of care therapy to improve pain control and dogs that had not yet received SAP were offered SAP injection.

Figure 2

Lateral (A) and anterior-posterior (B) views of the right antebrachium in a 9 year old, male, mixed breed dog diagnosed with osteosarcoma. There is an expansile moth-eaten lytic lesion in the distal radial metaphyseal region with speculated and sun burst periosteal reactions associated with it.

Figure 3

Kaplan-Meier product limit method and log rank analysis revealed that owners of dogs receiving standard of care therapy alone sought an additional intervention including additional analgesic medications or euthanasia for their animals significantly (p<0.002) sooner than owners of dogs that received substance-P saporin in addition to standard of care therapy.