Anthrapyrazole CI941: a highly active new agent in the treatment of advanced breast cancer.
Thirty-one patients with advanced breast cancer were treated with CI941, an anthrapyrazole structurally related to mitoxantrone. Patients had not previously been treated with anthracyclines or mitoxantrone, and 15 patients had not received any previous cytotoxic chemotherapy. CI941 was given at a dose of 50 mg/m2 by intravenous bolus injection every 21 days. Thirty patients were assessable for response, and all were assessable for toxicity. Two patients (7%) had complete responses (CRs), and 17 (56%) achieved partial responses (PRs; overall response rate, 63%; 95% confidence interval, 46% to 81%). The response rates in patients with and without prior chemotherapy were 63% and 64%, respectively. The median response duration was 37 weeks from start of treatment, with a maximum response duration of greater than 70 weeks. Median survival has not yet been reached. Leukopenia was the most frequently encountered toxicity, with a World Health Organization (WHO) grade greater than 3 occurring in 74% of courses. Thrombocytopenia and anemia were negligible. Only 10 patients (32%) had alopecia severe enough to wear a wig. There were no cardiac symptoms or events in any patient, but a slight median fall in left ventricular ejection fraction (LVEF) of 6% (from +7 to -12) during stress and 6% (from +14 to -14) at rest occurred. Other toxicities were mild, and the drug was generally well tolerated. CI941 is a very active and well-tolerated new agent in the treatment of advanced breast cancer, with neutropenia being the main toxicity.
Talbot
D C
DC
Breast Unit, Royal Marsden Hospital, London, United Kingdom.
Smith
I E
IE
Mansi
J L
JL
Judson
I
I
Calvert
A H
AH
Ashley
S E
SE
D000328:Adult; D000368:Aged; D000880:Anthraquinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004341:Drug Evaluation; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D007275:Injections, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D015993:Life Tables; D008875:Middle Aged; D016012:Poisson Distribution; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047069:Pyrazolones
D000880:Anthraquinones; D000970:Antineoplastic Agents; D011720:Pyrazoles; D047069:Pyrazolones; C050637:losoxantrone