Higher doses of mitoxantrone among men with hormone-refractory prostate carcinoma: a Cancer and Leukemia Group B study.
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/m(2) of mitoxantrone every 3 weeks, and 24 patients who had received pelvic irradiation (Arm II) were given 17 mg/m(2) on the same schedule. All patients received 40 mg of hydrocortisone in divided doses daily and GM-CSF at 500 microg/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 > or = 50% decline in their PSA, and 35% had a > or = 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/m(2)) 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/m(2)), and because the median survival is apparently comparable to standard dose mitoxantrone, this approach to HRPC cannot be recommended for Phase III testing.
Levine
Ellis G
EG
Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263-0001, USA. ellis.levine@roswellpark.org
Halabi
Susan
S
Roberts
John D
JD
Kaplan
Ellen B
EB
Rago
Randall
R
Atkins
James N
JN
Vogelzang
Nicholas J
NJ
D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008942:Mitoxantrone; D017430:Prostate-Specific Antigen; D006854:Hydrocortisone