Mitoxantrone Plus Prednisone – A Possible Fallback After Taxotere Failure

Men with metastatic hormone-refractory prostate cancer (mHRPC) who become docetaxel-refractory (no longer responsive to docetaxel therapy have no approved second line chemotherapy available. One could say that they have reached the proverbial brick wall. Where to go and what to do is not at all clear. Most of us do not want to just roll up and die, so what to do?

Many of the more creative and flexible oncologists reach deep down into their bags of tricks and often come up with the idea to fall back to the chemotherapy which was the standard of practice prior to the approval of docetaxel. They try to us mitoxantrone plus prednisone (MP), the old standby.

Thomas C, Hadaschik BA, Thüroff JW, Wiesner C., researchers at the Johannes-Gutenberg-Universität, Langenbeckstrasse 1, 55131, Mainz, Deutschland decided to evaluate the efficacy of this practice.

They took ten men with docetaxel-refractory mHRPC and treated them with MP. They evaluated prostate-specific antigen (PSA) remission, biochemical progression-free survival, and pain reduction.

Two of the ten men experienced partial PSA remission, “stable disease” in three other men, and progression in fiveof the men receiving MP. Progression-free survival was 8 months (mean) for men with partial PSA remission and 2 months (median) for the men with “stable disease.” Four of sevenmen reported pain reduction with MP. Grade 4 neutropenia was noted in only 10% of the men. The men who had experienced a decline of PSA while receiving docetaxel and MP had a progression-free survival of 11.5 months (median).

The researchers concluded that they see the indication for MP as being second-line chemotherapy in docetaxel-refractory patients with mHRPC who cannot be included in phase II/III studies. Even with only a moderate rate of partial PSA remission, every second man had an improvement in tumor-related pain, progression-free survival was prolonged, and the side effects of MP were comparatively low.

Given that there are no other alternatives and if you are not able to gain access to an appropriate clinical trial if seems that this is a route worth traveling.

Reference:
Thomas C, Hadaschik BA, Thüroff JW, Wiesner C., Urologe A. 2009 Jun 5. Epub ahead of print. doi:10.1007/s00120-009-2006-4

PubMed Abstract
PMID:19513599

Joel T Nowak, MA, MSW

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Tom Escott July 20, 2009 at 4:58 pm

I, too, was docetaxel-refractory with mHRPC in February 2009. I was in considerable pain from bone metastases. I was, however, fortunate to be accepted into a phase III clinical trial that included MP plus Ixabepilone, all FDA approved, but not in combination. I receive the M&I infusion every three weeks. The prednisone I take twice daily.

Since March, my PSA has dropped 87%, to 8.5. I was pain-free in the first month of the trial. Scans have not revealed any new cancer progression. The side effects are tolerable and have been reduced through weight loss, better diet, and exercise.