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Phase II study of mitoxantrone and ketoconazole for hormone‐refractory prostate cancer
Author(s) -
Eklund John,
Kozloff Mark,
Vlamakis Joy,
Starr Alexander,
Mariott Margaret,
Gallot Lilia,
Jovanovic Borko,
Schilder Lawrence,
Robin Erwin,
Pins Michael,
Bergan Raymond C.
Publication year - 2006
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21880
Subject(s) - medicine , ketoconazole , mitoxantrone , prostate cancer , neutropenia , gastroenterology , urology , phases of clinical research , chemotherapy , cancer , oncology , surgery , antifungal , dermatology
Abstract BACKGROUND Doxorubicin plus ketoconazole has exhibited significant activity in patients with advanced prostate cancer. However, overall and cardiac‐specific toxicity was reported to be high. Mitoxantrone has activity similar to that of doxorubicin, is less cardiotoxic, and is widely used to treat prostate cancer. The current study sought to evaluate the toxicity and activity of mitoxantrone plus ketoconazole in a cohort of patients with hormone‐refractory prostate cancer. METHODS Progression after medical or surgical castration and, for those patients receiving antiandrogens, progression after withdrawal was required, as was objective evidence of metastasis, castrate levels of testosterone, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and intact cardiac function. After enrollment onto a multicenter local consortium study, subjects were treated with mitoxantrone at a dose of 12 mg/m 2 intravenously every 3 weeks plus continuous oral ketoconazole at a dose of 400 mg 3 times daily and ascorbic acid at a dose of 250 mg. Replacement doses of hydrocortisone were given. RESULTS For 40 enrolled subjects, the median prostate‐specific antigen and ECOG performance status were 68 and 1, respectively, 53% had Gleason scores of 8 to 10, and all had metastasis. Predominant Grade 3/4 toxicities were: neutropenia in 13%, neutropenic fever in 10%, and anemia in 13%. Of 37 evaluable patients, 8% achieved a complete remission (CR) and 62% achieved a partial remission (PR), for a CR plus PR rate of 70%. For soft tissue and bone disease, overall response rates were 13% and 8%, respectively. The median progression‐free survival and overall survival were 10 months and 18 months, respectively. CONCLUSIONS Mitoxantrone plus ketoconazole is well tolerated, is active in hormone‐refractory prostate cancer, and should be studied further. Cancer 2006. © 2006 American Cancer Society.