Influence of the synthetic microtubule inhibitor erbulozole (P.I.N.N.) (R 55 104), a new tubulozole congener, and gamma irradiation on murine tumors in vivo.
Erbulozole (P.I.N.N.) (R 55 104) is a more water soluble congener of the synthetic microtubule inhibitor tubulozole (R 46 846) exhibiting a reversible antimicrotubular activity in vitro at a dose (1.56 x 10(-8) M) which is at least 10-fold lower. The compound also has an antiinvasive potential and shows antitumoral effects both in vitro and in vivo when administered appropriately. Eighty mg/kg R 55 104, given orally 6 h before or 3 h after radiotherapy, displays a prominent interactive effect with 10 Gy gamma irradiation in subcutaneous murine tumors which is similar to 160 mg/kg tubulozole administered 6 h before 10 Gy. The enhancing effect is also observed in a clinically relevant radiation dose fractionation schedule whereby eight fractions of 2 Gy each were pretreated 2 h before with 40 mg/kg R 55 104. Further study of this radiochemotherapeutic combination may lead to new clinical applications.
Distelmans
W
W
Janssen Research Foundation, Beerse, Belgium.
Van Ginckel
R
R
Vanherck
W
W
Willebrords
R
R
De Brabander
M
M
Wouters
L
L
Heeres
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004148:Dioxolanes / Q000008:administration & dosage / Q000627:therapeutic use*; D004149:Dioxoles / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D005354:Fibrosarcoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D051379:Mice; D008870:Microtubules / Q000187:drug effects*; D009368:Neoplasm Transplantation; D013997:Time Factors
D000970:Antineoplastic Agents; D004148:Dioxolanes; D004149:Dioxoles; C040422:tubulazole; C062050:erbulozole