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Click Here to Return to Proven Treatments Aminoglutethimide (Cytadren®) for Second Line Hormonal Therapy
NOTE: The manufacturer
of Cytadren has discontinued this drug. It is basically no longer available.
This is very unfortunate as it means another drug that was effective against
HRPC has been lost.
Abbreviations AG = Aminoglutethimide, sold as Cytadren® HC = Hydrocortisone, used as the glucocorticoid replacement.
Introduction
AG might be termed the "forgotten" second line hormone therapy as most urologists and oncologists do not prescribe it -- ketoconazole and DES are much more commonly used. One oncologist who uses it regularly is Robert Leibowitz, MD who feels the RR is higher with AG than for ketoconazole (see www.prostatepointers.org/leibowitz ). For an in-depth review of using Cytadren as a second line hormonal therapy, see, "Androgen Independent PC: How do You Treat Prostate Cancer That Has Progressed On Primary Androgen Deprivation Therapy? Part 2 : Secondary Hormonal Treatment Approaches, Revised October 1998" located at: http://www.prostate-cancer.org/education/andind/treatpc2.html
It might be appropriate to use Cytadren when ketoconazole stops working as part of a normal 2nd line hormonal therapy sequence or instead of using ketoconazole at all. It might also be useful during a break in chemotherapy to aid in extending the off chemo time. Clinical trials addressing this are, unfortunately, lacking.
Updates (2008)
In 2004, Kruit et al (7), published a paper in Anticancer Drugs that provides some useful data on response rates for heavily pre-treated patients who may have had prior chemotherapy.
Number of patients: 35, previous chemotherapy allowed.
Treatment start: 1st two weeks - AG 250mg 2x/day plus HC 20mg morning, 10mg afternoon, 10mg evening (breakfast, lunch, dinner is suggested as HC is usually taken with food.)
Treatment continuing: if no side effects such as skin rash, lethargy, nausea, and dizziness, then AG increased to 500mg 2x/day with the same HC of 40mg total. If any grade 2 toxicity, then HC was increased to 80mg/day until resolution of the grade 2 adverse event(s). Any grade 3 toxicity (other than skin toxicity) resulted in discontinuing AG.
Results: 13 patients of the 35 had a PSA response (PSA decrease ≥ 50%). Four other patients had PSA reductions of 37, 38, 40 and 43%. So about 50% of the patients had some PSA decrease. Responding patients had a median time to progression of 10.5 months. The median response duration was 9 months. Median survival for responding patients was 23 months. For 35 patients, median time to progressive disease evaluated by PSA was 4.5 months and median survival was 14.5 months.
Seven patients had measurable soft tissue metastases. There were 5 patients with stable disease and also 1 complete response and a partial response.
The Original Paper Here are some key facts: Aminoglutethimide must be administered with glucocorticoid replacement(e.g., hydrocortisone(HC) at standard replacement dosages - 30mg. If AG is stopped, the HC dosage must be tapered gradually over 2 weeks rather than stopped abruptly so that possible symptoms of adrenal suppression are avoided. References1-3
can be summarized as showing response rates (RR) ranging from 19% to 44%. Bone pain
was
relieved in about 30% of patients2,4.
But, Oh6
cites a paper by Dawson6 who reviewed 13 clinical trials of
aminoglutethimide plus hydrocortisone and found that there was an overall
partial response rate of 9%. Sartor5 et al, using a response criteria of a > 80% decline from baseline PSA, had a RR or 48%(14 of 29 patients); objective responses of 25%(3 of 12) and a median duration of PSA response of 4 months. Median duration of survival had not been reached, but was estimated to be 12+ months at the time of the report. NET: with a lot of pre-PSA era trials and a small number of PSA-era trials, the results for AG are difficult to pin down. The concurrent withdrawal of flutamide and the prior treatments(such as suramin) also confuse the results. Take the above numbers with all due caution as to the response you will see. The drug was originally developed as an anticonvulsant. AG effectively acts as if both adrenal glands were surgically removed, but its exact mechanism in the treatment of advanced prostate cancer is not clear as changes in androgen levels do not seem to correlate with tumor response. Some side effects to watch out for: Lethargy(sleepiness) (41%) and a skin rash (36%). Sometimes patients have a rash that begins
on the 10th day and subsides within a week after stopping treatment.
Occasionally fever along with the rash is also seen. There are rarer instances
of low platelet count, white blood cell count and anemia which usually disappear
upon stopping treatment. In the event they do not and are severe, then
they may be treatable with growth factors that stimulate bone marrow(as always,
discuss ramifications with your doctor.) For example, a patient recently reported the following: started a new treatment of cytadren plus hydrocortone - worked great for month, Felt great, cut psa from 72 to 34 -- but then either had flu and then a reaction to medicine or it was all the medicine -- had upset stomach, swelling in face, lips, skin rash. Note: some drugs may need dose changes if AG is taken concurrently -- see
the writeup at the PCRI website noted above.
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