Antitumor and radiosensitizing effects of (E)-2'-Deoxy-2'-(Fluoromethylene) cytidine, a novel inhibior of ribonucleotide diphosphate reductase on human colon carcinoma xenografts in nude mice.
[en] Antitumor and radiosensitizing effects of (E).2'-deoxy.2'-(fluromethyl
ene) cytidine (FMdC), a novel inhibitor of ribonucleotide reductase, were
evaluated on nude mice bearing s.c. xenografts and liver metastases of a
human colon carcinoma. FMdC given once daily or twice weekly has a
dose-dependent antitumor effect. The maximum tolerated dose In the mice
was reached with 10 mgi'kg applied daily over 12 days. Twice weekly
administration of FMdC reduced its toxicity but lowered the antitumor
effect. Treatment of preestablished liver micrometastases obtained via
intrasplenic injection of tumor cells, with 5 or 10 mgfkg FMdC, signifi
candy prolonged the survival of the mice as compared to controls
(P < 0.025 and P < 0.001, respectively). Ten mg/kg resulted in longer
survival than S mg/kg FMdC (P < 0.05). Radiotherapy alone of s.c.
xenografts (10 fractions over 12 days) yielded the radiation dose required
to produce local tumor control in 50% of the treated mice (TCD@O)of 43.0
Gy. When combined with FMdC, TCDsawas reduced to 22.5 and 19.0 Gy
at doses of 5 and 10 mg/kg given i.p. 1 h before each irradiation, respec
tively. The corresponding enhancement ratios were 1.91 and 2.43, respec
lively. FMdC produced moderate and reversible myelosuppression. When
5 mg/kg FMdC was combined with irradiation, there was no increased
skin or hematological toxicity as compared to radiotherapy or FMdC
alone. At the 10 mg/kg level, however, lower leukocyte counts were
observed. These results show that FMdC appears to be a potent anticancer
drug and radiosensitizer
Disciplines :
Hematology Oncology
Author, co-author :
Sun, Lin-Quan; University Hospital of Lausanne (CHUV > Department of Pathology
Li, Ye-Xiong; University Hospital of Lausanne (CHUV) > Pathology
Guillou, Louis; University Hospital of Lausanne (CHUV) > Pathology
Mirimanoff, René-Olivier; University Hospital of Lausanne (CHUV) > Pathology
COUCKE, Philippe ; University Hospital of Lausanne (CHUV) > Radiothérapie
Language :
English
Title :
Antitumor and radiosensitizing effects of (E)-2'-Deoxy-2'-(Fluoromethylene) cytidine, a novel inhibior of ribonucleotide diphosphate reductase on human colon carcinoma xenografts in nude mice.
Publication date :
1997
Journal title :
Cancer Research
ISSN :
0008-5472
eISSN :
1538-7445
Publisher :
American Association for Cancer Research, Inc. (AACR), Baltimore, United States - Maryland
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