Higher doses of mitoxantrone among men with hormone‐refractory prostate carcinoma

• Published in: Cancer 2002-02, Vol.94 (3), p.665-672
• Main Authors: Levine, Ellis G., Halabi, Susan, Roberts, John D., Kaplan, Ellen B., Rago, Randall, Atkins, James N., Vogelzang, Nicholas J.
• Format: Article
• Language: English
• Subjects: clinical trials; drug therapy; granulocyte‐macrophage colony‐stimulating factor; mitoxantrone; prostate neoplasms
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.10217

BACKGROUND Mitoxantrone in combination with a low‐dose glucocorticoid has been shown to produce more favorable outcomes among men with hormone‐refractory prostate carcinoma than glucocorticoid alone. Therefore, the authors sought to determine the safety and activity of higher doses of mitoxantrone in combination with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and a glucocorticoid in preparation for a possible Phase III trial comparing standard to dose‐escalated mitoxantrone. METHODS This Phase II trial enrolled 45 patients from October 1996 to March 1998. Twenty‐one patients without pelvic irradiation (Arm I) received 21 mg/m2 of mitoxantrone every 3 weeks, and 24 patients who had received pelvic irradiation (Arm II) were given 17 mg/m2 on the same schedule. All patients received 40 mg of hydrocortisone in divided doses daily and GM‐CSF at 500 μg/daily for a minimum of 10 days per cycle beginning on the third day of the cycle. RESULTS In Arm I, 33% of assessable patients achieved a partial response, 50% had a ≥ 50% decline in their PSA, and 35% had a ≥ 75% decline in PSA values. The comparable numbers in Arm II were 24%, 48%, and 35%, respectively. The median survival times were 12 months in Arm I and 14 months in Arm II. Treatment had to be discontinued in 13% of patients because of thrombocytopenia. No other significant toxicities were encountered. CONCLUSIONS Higher doses of mitoxantrone (17 and 21 mg/m2) were associated with activity comparable to many estramustine combinations and generally were well tolerated. However, because the degree and frequency of thrombocytopenia were greater than that observed with standard dose mitoxantrone (12–14 mg/m2), and because the median survival is apparently comparable to standard dose mitoxantrone, this approach to HRPC cannot be recommended for Phase III testing. Cancer 2002;94:665–72. © 2002 American Cancer Society. DOI 10.1002/cncr.10217 A regimen including higher doses of mitoxantrone has activity comparable to many estramustine regimens and is well tolerated. However, the regimen cannot be recommended for Phase III testing, because the frequency of thrombocytopenia was higher than anticipated.