Response of rat prostate and lung tumors to ionizing radiation combined with the angiogenesis inhibitor AMCA.
OBJECTIVE
To determine whether radiation combined with Trans-4-AminoMethyl Cyclohexane carboxylic Acid (AMCA, or tranexamic acid, Cyklokapron) results in a better tumor response than radiation alone.


METHODS
We evaluated the responses of the L44 lung tumor in BN rats and R3327-MATLyLu (MLL) prostate tumor in Copenhagen rats, to single and fractionated X-ray doses with and without AMCA (1.5 g/kg). Tumors were grown subcutaneously in the flank of the animal. AMCA was administered subcutaneously twice daily for at least 2 weeks. Response to treatment was evaluated according to excess growth delay and specific growth delay.


RESULTS
L44 and MLL tumors treated with AMCA only experienced a non-significant growth delay. L44 tumors treated with 4 daily dose fractions of 2.5 Gy had a significant excess and specific growth delay when treated with AMCA, the enhancement ratio was 1.6-1.7. The enhancement ratio based on the calculated excess biologically effective dose of the linear-quadratic concept was 1.4-1.5. MLL tumors treated with a single dose of 20 Gy and AMCA had no significant excess growth delay.


CONCLUSIONS
The enhancement ratio of 1.4-1.7 for the L44 tumor, but not for the MLL tumor, due to AMCA treatment, indicates that AMCA may potentiate the anti-tumor effect of ionizing radiation in distinct tumor types.
Kal
Henk B
HB
Department of Radiotherapy, University Medical Centre, Utrecht, The Netherlands. H.B.Kal@azu.nl
Struikmans
Henk
H
Gebbink
Martijn F B G
MF
Voest
Emile E
EE
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000933:Antifibrinolytic Agents / Q000008:administration & dosage; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011839:Radiation, Ionizing; D051381:Rats; D014148:Tranexamic Acid / Q000008:administration & dosage*; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid