Phase II study of KRN8602, 3 '-deamino-3 '-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride, MX2 center dot HCl in patients with metastatic breast cancer

Purpose: KRN8602 (3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride, MX2 . HCl) is a newly developed anthracycline that has been found to be effective against multidrug-resistant tumor cells in vitro and in vivo. In order to clinically confirm these promising preclinical observa tions, we performed a phase II trial of KRN8602 in patients with anthracycl ine-resistant metastatic breast cancer. Methods: Of 41 patients registered with metastatic breast cancer, 37 were eligible and were given at least two cycles of KRN8602 15 mg/m(2) per day at 3-4 week intervals by intravenous bolus injection on days 1, 2, and 3. Results: Of the 37 patients, 6 (16.2%, with a 95% confidence interval of 4.3-28.1%) had a partial response (PR). No complete responses (CRs) were observed. The difference between response rates according to prior history of anthracycline administration was not si gnificant. Myelosuppression was moderately severe, with grade 3 or 4 leukop enia occurring in 65%. Severe nausea/vomiting was observed in 44% of the pa tients. Conclusions: The results indicate that KRN8602 has modest activity in refractory metastatic breast cancer and is associated with relatively se vere toxicity. Furthermore, the preclinical finding that KRN8602 overcomes anthracycline resistance was not reliably reproduced in this clinical phase II trial.