Brain metastasis, new drugs, and future treatment of mCRPC

A new article on the Medcape Oncology web site discusses progress in the treatment of metastatic, catsration-resistant prostate cancer (mCRPC) and the specific relationship between risk for brain metastasis and the extension of overall survival.

Brain metastasis in men with advanced, metastatic prostate cancer is not common, and (at least currently) appears to occur in less than 3 percent of all men with hormonally treated prostate cancer. However, the paper by Caffo et al. on the Medscape web site (originally published in Future Oncology) suggests that the incidence of brain metastasis may have been rising slowly over the years, and suggests that this may be associated with the fact that men are living longer with metastatic disease because (ever since the introduction of docetaxel + prednisone as a first-line form of chemotherapy) the range of effective treatment options has been slowly (and recently more rapidly) increasing. In a related paper, Caffo et al. also discuss the incidence of brain metastasis among prostate cancer patients at their Italian institution over the past nearly 20 years.

It is not our intention to discuss Caffo et al.’s hypotheses in detail. Interested readers should look at the original paper on the Medscape web site. However, we would point out that some of the suggestions made by Caffo et al. do not seem justifiable to us. As an example, at one point they suggest that the median survival of men with mCRPC may be as much as:

  • 29.0 months for patients treated first with docetaxel + prednisone and then with cabazitaxel + prednisone and
  • 32.6 months for patients treated first with docetaxel + prednisone and then with abiraterone acetate + predisone.

Such a suggestion is simply not justifiable. The authors came to this conclusion by just adding together the median survival times from clinical trials of men with mCRPC treated with docetaxel and subsequently with either abiraterone acetate or cabazitaxel. They seem to have forgotten that any survival time for men treated with docetaxel would need to be cut down by any amount of survival after progression on docetaxel (since that would be when treatent with the next drug would be initiated).

It will be a while before we have a clear idea of the real survival benefit of sequential treatment with (say) docetaxel, then abiraterone, and then cabazitaxel, and in fact it seems likely that a more common sequence will be abiraterone, then docetaxel, and then cabazitaxel. The latter sequence may have a very different therapeutic impact (even without the introduction of enzalutamide and other forthcoming agents).

We do know, however, that we are slowly extending the lives of men with mCRPC (albeit at a considerable financial cost and a considerable cost in terms of side effects and complications of such treatment whendrugs like docetaxel and cabazitaxel are needed). The primary hypothesis put forward by Caffo et al. — that such extended survival may increase the incidenced of brain metastasis in men with mCRPC is far from unreasonable.

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