High-dose
Ketoconazole And Hydrocortisone For Hormone Refractory Prostate Cancer
M.
Scholz, S. Strum, P. Mittelman, Prostate Cancer Research Institute,
LosAngeles, CaliforniaEighty HRPC patients were retrospectively
evaluated for factors predicting a longer
response to ketoconazole (keto).
Duration
of response was measured from start of keto to PSA progression or last
follow-up. PSA progression was defined as the first of two consecutive
PSA levels 50% above PSA (PSAN) or above baseline PSA (bPSA) if no nadir
occurred. At low PSA levels, progression was defined
as a PSA rise of 2 ng/dl over PSAN or bPSA if no PSAN occurred (this definition
was used whenever a 50% PSA rise would have been less than 2 ng/dl).
The
median age of the patients was 68. Average baseline PSA was 108 (median
21). Median baseline
PSA doubling time was 84 days. The
keto dose was 200 mg every 8 hours increased to 400 after the first
7 days with hydrocortisone 20-mg b.i.d. (twice a day).
Sixty-one
patients have progressed. Eleven are still responding after a mean of
24 months (range 3-66). Four responders stopped keto after 2, 12, 17
and 25,
months for visual problems, azotemia, or lassitude (2 pts.). Two died of
unrelated causes after 3 and 30 months. Two were lost to follow-up,
both after
3 months. Average treatment time was 15 months (median 8).
The
median number of months response for PSA percent declines of <50,
51-75, and >75were 3, 6.5, and 17.5 months, respectively. A baseline
PSA <10.0 was the only significant
pre-therapy predictor of response duration in multivariate analysis
(p<0.003). PSA nadir was the best predictor of response duration overall
(p< 0.0002).
| PSA |
Number
of patients |
Median
# months response |
| Baseline
PSA < 10 |
25 |
25 |
| Baseline
PSA > 10 |
55 |
4 |
| PSA
nadir < 0.2 |
14 |
40 |
| PSA
nadir 0.2 - 4.0 |
20 |
18 |
| PSA
nadir 4.1 - 10 |
11 |
8 |
| PSA
nadir > 10 |
35 |
4 |
Conclusion:
A prolonged response with ketoconazole is far more common in HRPC patients
if treatment is initiated before the bPSA rises above 10.
