Bisantrene (
NSC 337766) is an anthracenedicarboxaldehyde
hydrazone demonstrating a wide spectrum of activity in animal
tumor model systems with no evidence of
cardiotoxicity or
alopecia, in contrast to
doxorubicin. Thirty-three women with advanced
adenocarcinoma of the breast were treated with 260 mg/m2 IV every 3 weeks. All patients had received at least one prior
combination chemotherapy regimen for metastatic disease and 32/33 were refractory to
doxorubicin. Of 28 patients evaluable for response one had a partial response lasting 10 weeks and three patients had stable disease for 22, 22, and 9 weeks. The most significant toxicities were nonhematologic:
nausea and
vomiting (41%), phlebitic reactions (38%),
hypotension, one fatal
anaphylactic reaction, and the development of a 7th
cranial nerve palsy during
drug infusion. Hematologic toxicity,
leukopenia, was dose-limiting but manageable without associated
infections or
bleeding. These results indicate that
bisantrene in this dose and schedule is not a useful
drug in heavily pretreated
breast cancer patients. The incidence and severity of phlebitic reactions limited venous access and adversely affected patient compliance. Preliminary results of other phase II
breast cancer trials indicate a similar spectrum of toxicity but suggest more significant antitumor activity even in patients previously treated with
doxorubicin. Trials conducted in patients with minimal prior treatment and with
bisantrene administered via central line appear warranted for definitive assessment of the activity of this agent in
breast cancer.