Importance of administration method in high-dose anticancer chemotherapy from toxicological standpoint in rats.
We examined death rates in Fisher rats when chemotherapeutic drugs were administered in a prescribed amount by either a single or divided dose. Lower death rates were observed when nimustine hydrochloride (ACNU) was given in a divided dose, or when cyclophosphamide (CY), vindesine sulfate (VDS) or vincristine (VCR) was administered as a single dose. Lower hematological toxicity was observed when ACNU was administered in 2 doses and CY in a single dose. With etoposide, we did not observe any significant difference between the two administration methods. In a combination study with ACNU and VDS, we observed lower toxic death rates when the dose of ACNU was split and VDS was given as a single dose. ACNU-induced death was substantially reduced by syngeneic bone marrow support or granulocyte colony-stimulating factor treatment. Our experiments indicate that the toxicity of the administration of chemotherapeutic agents may be significantly modified by altering the time course of administration. This would hopefully result in reducing the chemotherapy-related mortality associated with high-dose anticancer chemotherapy.
Mizushima
Y
Y
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Konishi
K
K
Morikage
T
T
Yano
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity; D001772:Blood Cell Count; D016026:Bone Marrow Transplantation; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity; D005047:Etoposide / Q000008:administration & dosage / Q000633:toxicity; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006410:Hematopoiesis / Q000187:drug effects; D008297:Male; D015376:Nimustine / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage / Q000633:toxicity; D014751:Vindesine / Q000008:administration & dosage / Q000633:toxicity
D000970:Antineoplastic Agents; D015376:Nimustine; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D014751:Vindesine