THE "NEW" PROSTATE CANCER INFOLINK

Two European studies that have just been published appear to validate the long-term concept of intermittent hormone therapy (IHT).

The first study, carried out by Calais da Silva et al., was designed to determine whether intermittent therapy is associated with a shorter time to progression.

A total of 766 patients with locally advanced or metastatic prostate cancer received a 3-month induction treatment. Patients received cyproterone acetate (CPA) 200 mg for 2 weeks and then monthly depot injections of a luteinizing hormone-releasing hormone (LHRH) analog plus 200 mg of CPA daily during induction.

The 626 patients whose PSA level decreased to < 4 ng/ml or to 80 percent below the initial value were randomized into the clinical trial. Patients randomized to the intermittent arm ceased treatment, while those randomized to the continuous arm received 200 mg of CPA daily plus an LHRH analog.

The results of this trial were as follows:

• 127 patients from the intermittent arm and 107 patients from the continuous arm progressed, with a hazard ratio (HR) of 0.81.
• There was no difference in survival, with an HR of 0.99 and 170 deaths in the intermittent arm and 169 deaths in the continuous arm.
• The greater number of cancer deaths in the intermittent treatment arm (106 vs 84) was balanced by a greater number of cardiovascular deaths in the continuous arm (52 vs 41).
• Side-effects were more pronounced in the continuous arm.
• Men treated with intermittent therapy reported better sexual function.
• Median time off therapy for the intermittent patients was 52 weeks.

The authors of this study concluded that, “IHT should be considered for use in routine practice because it is associated with no reduction in survival, no clinically meaningful impairment in QoL, better sexual activity, and considerable economic benefit to the individual and the community.”

The second study, by Prapotnich et al., presents data from a single-center study of  intermittent androgen deprivation carried out between 1992 and 2008.

In this study, 566 patients with prostate cancer were initially enrolled.

• 218/566 patients had biochemical recurrence after local treatment for prostate cancer
• 348/566 patients had micro- or macro-metastatic disease.
• The on-treatment period (ONTP) consisted of 3-monthly injections of an LHRH agonist combined with daily oral androgen receptor antagonist therapy.
• The off-treatment period (OFTP) was indicated when the PSA level was < 4 ng/ml.
• Criteria for resumption of hormonal therapy were a PSA level of  >20 ng/ml or clinical symptoms.
• Cancer specific survival curves were computed according to the Kaplan-Meier method.

The results of this second study can be summarized as follows:

• Median follow-up was 81 months (range, 12 to 230 months).
• Median patient age was 74.7 years (range 52-92 years).
• Median Gleason score at diagnosis was 7 (range 3 to 9).
• Median initial PSA was 17 ng/ml (range 0.4 to 433 ng/ml).
• Cycle duration decreased progressively from 23 months for the first cycle to 10 months for the 12th cycle.
• The number of patients who became hormone resistant was 182 (32 percent).
• Median cancer-specific survival probability for the series is 12 years (range 10.8 to an infinite number of years).
• No previous treatment group showed a higher cancer-specific survival probability compared to the group with biochemical recurrence.
• Multivariate analysis of cancer-specific survival showed that age, initial Gleason score, and initial PSA level were significant factors affecting mortality.

In this study the authors conclude that intermittent hormone therapy “is an acceptable treatment in different stages of [prostate cancer]. Duration of cycle decreased progressively during therapy. Age, Gleason score and PSA are factors predicting mortality.”

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