High-dose bicalutamide as second-line hormone therapy in CRPC patients

Historically there have been few really compelling data available to support the use of an additional or alternative antiandrogen as a second-line agent to extend either progression-free or overall survival of castration-resistant prostate cancer (CRPC) patients who progress after first-line hormone therapy (whether they have been treated by orchiectomy or medical castration with an LHRH agonist).

A recent article by Lodde et al. reports data on the use of high-dose bicalutamide as salvage therapy for patients with non-metastatic, castration-resistant prostate cancer. (In other words, the patients must already have received either surgical or medical castration and an antiandrogen.)

This was a small, single-institution, prospective trial. It included just 38 patients who had been surgically or medically castrated, who had no bony metastases, and who had increasing PSA values after previous antiandrogen therapy. All patients were treated with a daily dose of bicalutamide 150 mg. Relevant clinical evaluations and serum PSA testing were carried out every 3 months. Bone scans were carried out if there was a PSA increase or if there were any symptoms suggestive of disease progression.

Response criteria were defined as follows:

  • A positive response to therapy was any PSA decline from baseline.
  • A partial response was a PSA decline from baseline of ≥ 50 percent but < 85 percent
  • A complete response was a PSA decline from baseline of  ≥ 85 percent.
  • Duration of response was the time from initiation of therapy until PSA increased by either ≥ 25 percent or by ≥ 2 ng/ml from the nadir, whichever occurred sooner.

Results of the trial were as follows:

  • Average (mean) follow-up was 34.5 months (range, 3 to 75.2 months).
  • A PSA response (a decline of any amount) occurred in 17/38 patients (44.7 percent).
  • A partial response occurred in 10/38 patients (26.3 percent)
  • A “complete” response occurred in  7/38 patients (18.4 percent).
  • For partial responders, the median duration of response was 18.5 months.
  • For “complete” responders, the median duration of response was 37.4 months.
  • For all responders, the median time to metastasis was 52.5 months.
  • For all non-responders, the median time to metastasis was 15.7 months.

The authors conclude that high-dose bicalutamide can induce a second response in nearly half the castration-resistant prostate cancer patients who are free of metastasis. The duration of  this response is more than 1.5 years on average, and responders have prolonged metastasis-free survival.

Because this study is not based on randomized, blinded, or placebo-controlled data, it is hard to know how definitive it may be. It appears appear clear, however, that some 20 percent of patients were getting a strong response to second-line, high-dose bicalutamide, and that this response was associated with a significant delay in their PSA progression and their time to metastatic disease compared to the non-responders. It would be of some interest to know whether the responders were generally patients with longer PSA doubling times.

It should be noted that an earlier, small Southwest Oncology Group study (published by Kucuk et al. in 2001) also used bicalutamide 150 mg/d in advanced prostate cancer patients who were progressing after maximal androgen deprivation therapy. This study showed palliative impact but no strong effect on time to disease progression, but the study included patients with evident metastatic disease.

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