Evaluation of Clostridium novyi-NT spores in dogs with naturally occurring tumors.
OBJECTIVE
To establish the maximum tolerated dose of Clostridium novyi-NT spores in tumor-bearing dogs and evaluate spore germination within tumors and tumor response.


METHODS
6 client-owned dogs.


METHODS
A standard dose-escalation study was planned, with maximum tolerated dose defined as the highest dose at which 0 or 1 of 6 dogs had dose-limiting toxicoses (DLT). Dogs received 1 dose of C. novyi-NT spores i.v.. Toxicoses were graded and interventions performed according to specific guidelines. Grade 3 or higher toxicosis or any toxicosis combination that substantially affected patient status was considered DLT. Clinical response was measured by use of response evaluation criteria in solid tumors at 28 days.


RESULTS
The first 2 dogs had DLT. The dose was decreased. Two of the next 4 dogs had DLT; therefore, dose administration was stopped because the study endpoint had been reached. The most common toxicosis was fever (n = 6 dogs). Two dogs developed abscesses (1 within a nasal carcinoma and 1 splenic abscess) attributable to C. novyi-NT infection; both required surgical intervention. Clostridium novyi-NT was cultured from 1 of 6 tumors. Five dogs were available for response assessment (4 had stable disease; 1 had progressive disease).


CONCLUSIONS
Results indicated that C. novyi-NT can germinate within tumors of dogs. Toxicosis, although common and sometimes severe, was manageable with treatment. Further studies in dogs with superficial tumors may allow for continued dose escalation and provide information for use in clinical trials in veterinary and human oncology.
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ekrick@vet.upenn.edu
Erika L
EL
Krick
Karin U
KU
Sorenmo
Shelley C
SC
Rankin
Ian
I
Cheong
Barry
B
Kobrin
Katherine
K
Thornton
Kenneth W
KW
Kinzler
Bert
B
Vogelstein
Shibin
S
Zhou
Luis A
LA
Diaz
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D003013:Clostridium; D003015:Clostridium Infections / Q000382:microbiology; D004283:Dog Diseases / Q000188:drug therapy / Q000382:microbiology* / Q000628:therapy*; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000188:drug therapy / Q000382:microbiology / Q000628:therapy / Q000662:veterinary*; D030781:Organisms, Genetically Modified; D013171:Spores, Bacterial
D000970:Antineoplastic Agents