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 × 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.