A PHASE-II MULTIINSTITUTIONAL STUDY OF ESTRA-1,3,5(10)-TRIENE-3,17-BETA-DIOL, 3-BENZOATE, S(2-CHLOROETHYL)AMINO]PHENYL]-1-OXOBUTOXY]ACETATE] (KM2210), A NOVEL ANTITUMOR AGENT, FOR ADVANCED AND RECURRENT BREAST-CARCINOMA

In order to evaluate the efficacy of Estra-1,3,5(10)-Triene-3, 17 beta -Diol, 3-Benzoate, 17[[4-[4-[Bis(2-Chloroethyl) Amino] Phenyl]-1-Oxobu toxy] Acetate] (KM2210), a multiinstitutional cooperative Phase II stu dy was performed in patients with measurable advanced and recurrent br east cancer. Two hundred miligrams of KM2210, a conjugate of chlorambu cil and 17 beta-estradiol, were administered orally daily for more tha n 4 weeks to each patient. According to the WHO criteria of response, 103 evaluable cases were assessed. Complete response was obtained in 9 cases, partial response in 19, no change in 39 and progressive diseas e was observed in 36. The overall response rate was 27.2% (28/103). Th e response rate was higher in patients without prior treatment than in those with prior treatment. However, KM2210 was also effective agains t breast cancers treated previously with tamoxifen, anthracyclines and their combinations, showing, response rates of 25.5%, 22.0% and 29.6% respectively, suggesting that this agent is also effective on breast carcinomas which were insensitive to tamoxifen and anthracyclines. For efficacy classified in terms of metastatic lesions, the response rate was significantly higher in soft tissues than in other involved organ s, and the responsive rate of bone metastasis was limited. Bone marrow suppression, including leukopenia and thrombocytopenia, was thought t o be the dose-limiting toxicity of KM2210. Genital bleeding doe to the released estrogen was observed as a characteristic side effect. KM221 0 is considered to be useful for the treatment of advanced and recurre nt breast cancer when administered at a dose level of 200 mg per day f or more than 4 weeks.