Clinical studies of (2''R)-4'-O-tetrahydropyranyl adriamycin (THP)

(2'' R)-4'-O-Tetrahydropyranyl Adriamycin (THP) is a new antitumor agent discovered among series of similar anthracycline compound synthesized by Umezawa et al. Phase I study revealed dose limiting factor of leukopenia with upper GI toxicity. Alopecia, cardiac failure and transient hepatic failure were extremely mild. Definite responses were demonstrated in acute leukemia, lymphoma, ovarian carcinoma, head and neck carcinoma, breast carcinoma and GU carcinoma. Pharmacokinetic studies revealed rapid cell uptake and outputs in bile (20%) and urine (8%) in 24 hours. Transfer to third spaces were poor but definite. In vivo a part of THP was converted to ADM in the liver, but not in other tissues including tumors. THP would be an extremely interesting compound, because of comparable spectrum of responses to various tumors with extremely low toxicity compared with other anthracycline compounds.