Evaluation of dexamethasone as a chemoprotectant for CCNU-induced bone marrow suppression in dogs.
In mice and people, administering corticosteroids before chemotherapy can reduce the severity of myelosuppression without reducing antitumour effects. This study investigated whether pretreatment with dexamethasone would reduce the incidence of grade 4 neutropenia in dogs receiving CCNU. Twenty-five dogs received dexamethasone [0.1 mg kg(-1) per os (PO) every 12 h] for 5 days and on the sixth day received CCNU (90 mg m(-2) PO). Historical dogs (n = 67) received CCNU alone (90 mg m(-2) PO). Forty-five percent of historical dogs had grade 4 neutropenia, while 64% of dogs pretreated with dexamethasone had grade 4 neutropenia (P = 0.16). Dexamethasone plasma levels were quantified by enzyme-linked immunosorbent assay in three healthy dogs. Peak plasma concentrations after a single oral 0.1-mg kg(-1) dose were <80 ng mL(-1), the minimum level associated with chemoprotective effects of dexamethasone in people. Pretreatment with dexamethasone did not reduce the incidence of grade 4 neutropenia in dogs receiving CCNU.
Intile
J L
JL
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Rassnick
K M
KM
Bailey
D B
DB
Al-Sarraf
R
R
Chretin
J D
JD
Balkman
C E
CE
Flory
A B
AB
Kiselow
M A
MA
Wakshlag
J J
JJ
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D001853:Bone Marrow / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004283:Dog Diseases / Q000097:blood* / Q000188:drug therapy*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005938:Glucocorticoids / Q000494:pharmacology*; D008130:Lomustine / Q000008:administration & dosage; D009503:Neutropenia / Q000097:blood / Q000188:drug therapy / Q000662:veterinary*; D009518:New York; D012582:Schools, Veterinary; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D005938:Glucocorticoids; D008130:Lomustine; D003907:Dexamethasone