Phase II study of mitoxantrone and ketoconazole for hormone-refractory prostate cancer

John Eklund, Mark Kozloff, Joy Vlamakis, Alexander Starr, Margaret Mariott, Lilia Gallot, Borko Jovanovic, Lawrence Schilder, Erwin Robin, Michael Pins, Raymond Bergan

Research output: Contribution to journalArticle

19 Citations (Scopus)

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/m2 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.

Original languageEnglish (US)
Pages (from-to)2459-2465
Number of pages7
JournalCancer
Volume106
Issue number11
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

Fingerprint

Mitoxantrone
Ketoconazole
Prostatic Neoplasms
Hormones
Doxorubicin
Neoplasm Metastasis
Androgen Antagonists
Neoplasm Grading
Bone Diseases
Castration
Prostate-Specific Antigen
Neutropenia
Ascorbic Acid
Disease-Free Survival
Hydrocortisone
Testosterone
Anemia
Fever
Survival

Keywords

  • Chemotherapy
  • Hormone refractory
  • Metastasis
  • Phase II
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Eklund, J., Kozloff, M., Vlamakis, J., Starr, A., Mariott, M., Gallot, L., ... Bergan, R. (2006). Phase II study of mitoxantrone and ketoconazole for hormone-refractory prostate cancer. Cancer, 106(11), 2459-2465. https://doi.org/10.1002/cncr.21880

Phase II study of mitoxantrone and ketoconazole for hormone-refractory prostate cancer. / Eklund, John; Kozloff, Mark; Vlamakis, Joy; Starr, Alexander; Mariott, Margaret; Gallot, Lilia; Jovanovic, Borko; Schilder, Lawrence; Robin, Erwin; Pins, Michael; Bergan, Raymond.

In: Cancer, Vol. 106, No. 11, 01.06.2006, p. 2459-2465.

Research output: Contribution to journalArticle

Eklund, J, Kozloff, M, Vlamakis, J, Starr, A, Mariott, M, Gallot, L, Jovanovic, B, Schilder, L, Robin, E, Pins, M & Bergan, R 2006, 'Phase II study of mitoxantrone and ketoconazole for hormone-refractory prostate cancer', Cancer, vol. 106, no. 11, pp. 2459-2465. https://doi.org/10.1002/cncr.21880
Eklund J, Kozloff M, Vlamakis J, Starr A, Mariott M, Gallot L et al. Phase II study of mitoxantrone and ketoconazole for hormone-refractory prostate cancer. Cancer. 2006 Jun 1;106(11):2459-2465. https://doi.org/10.1002/cncr.21880
Eklund, John ; Kozloff, Mark ; Vlamakis, Joy ; Starr, Alexander ; Mariott, Margaret ; Gallot, Lilia ; Jovanovic, Borko ; Schilder, Lawrence ; Robin, Erwin ; Pins, Michael ; Bergan, Raymond. / Phase II study of mitoxantrone and ketoconazole for hormone-refractory prostate cancer. In: Cancer. 2006 ; Vol. 106, No. 11. pp. 2459-2465.
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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/m2 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.",
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AU - Eklund, John

AU - Kozloff, Mark

AU - Vlamakis, Joy

AU - Starr, Alexander

AU - Mariott, Margaret

AU - Gallot, Lilia

AU - Jovanovic, Borko

AU - Schilder, Lawrence

AU - Robin, Erwin

AU - Pins, Michael

AU - Bergan, Raymond

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N2 - 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/m2 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.

AB - 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/m2 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.

KW - Chemotherapy

KW - Hormone refractory

KW - Metastasis

KW - Phase II

KW - Prostate cancer

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