Combined use of gemcitabine and radiation in mice.
The aim of this study was to explore, in a murine tumor, if the effectiveness of radiation, in doses and schedules commonly used in clinical practice is potentiated by the combined use of the recently developed drug gemcitabine. Gemcitabine (30-360 mg/kg b.w.) was administered i.p. in female C3D2F1 mice bearing a mammary adenocarcinoma alone or combined with X-rays. Firstly, gemcitabine (single administration) was administered alone or at 20 min, 4 h, and 24 h before X-ray treatments. The significant effect observed only at 24 h time interval, depended on the X-ray dose and not on the gemcitabine dose. Secondly, 4 gemcitabine administrations every 3 days were used in fractionated combined schedules (overall treatment time of 10 days). We studied the relationship among different doses of gemcitabine, alone or combined with 10 daily X-ray treatments (2 Gy/fraction). We observed an interactive effect of gemcitabine up to its threshold dose of 60 mg/kg/fraction. Furthermore, 10 X-ray daily treatments and 4 X-ray treatments every 3 days (total doses 20-40 Gy) were performed with gemcitabine 60 mg/kg/fraction to study the effect of different doses and schedules of X-rays. Tumor growth delays increase with higher X-ray doses, and this occurs more with 4 X-ray treatments than with 10 X-ray treatments. Our results re-affirm the uselessness of high gemcitabine doses, and indicate the effectiveness of combined gemcitabine-radiation fractionated protocols.
Cividalli
A
A
Section of Toxicology and Biomedical Sciences, ENEA, Casaccia, Via Anguillarese, 00060 Rome, Italy. cividalli@casaccia.enea.it
Livdi
E
E
Ceciarelli
F
F
Fontana
G
G
Altavista
P
P
Cruciani
G
G
Danesi
D T
DT
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000532:radiotherapy*; D051379:Mice; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D011859:Radiography; D012867:Skin / Q000000981:diagnostic imaging / Q000187:drug effects; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine