The preliminary results from the first 21 patients treated in the Phase I combination trial with cisplatin showed similar results, with 14 of the patients experiencing stable disease and half of those 14 patients having durable stable disease for more than six cycles of therapy. Toxicities were mainly hematological and were manageable and reversible in this heavily pretreated patient population. Phase II studies using this combination in patients resistant to standard therapy are planned.
The Phase I, multicenter, dose-escalation study of brostallicin in combination with cisplatin (cDDP) was conducted in patients with recurrent or metastatic solid tumors. Treatment cycles were three weeks. Brostallicin was escalated from 5 to 7 to 9mg/m2 with a fixed dose of cDDP of 75mg/m2.
The trial is based on data demonstrating tumors with high levels of GSH/GST, common in platinum-resistant disease, are more susceptible to the killing effects of brostallicin. Brostallicin, a novel synthetic second-generation DNA minor groove binder, has potent cancer killing activity and has demonstrated synergism in combination with standard cytotoxic agents as well as with newer targeted therapies in preclinical experimental tumors models.