THE "NEW" PROSTATE CANCER INFOLINK

The results of early, large, randomized trials of intermittent (IADT) vs. continuous androgen deprivation therapy (CADT) have provided conflicting results. However, one of the flaws in early trials was the failure to ensure that men enrolled into these trials all actually had an optimal initial response to androgen deprivation (ADT).

The ICELAND trial seems to have helped to resolve this problem — based on the abstract of a paper to be presented by Schulman et al.  at the upcoming annual meeting of the American Urological Association. (See abstract no. MP73-20 in the Prostate Cancer: Advanced I session.)

The ICELAND trial was a large multi-center study conducted within the European Union. It initially enrolled 933 men with with relapsing M0 or locally advanced prostate cancer after radical prostatectomy or radiation therapy. All patients also had to have a Gleason score ≥6, and a life expectancy ≥ 5 years. It is important to note that this trial did not include any patients with metastatic disease.

The 933 patients all were treated with a 6-month ADT induction regimen of leuprolide acetate 3-month depot 22.5 mg + bicalutamide 50 mg/day for the first month. After this initial 6-month induction therapy, patients with a PSA level of ≤ 1 ng/ml were randomized 1:1 to either IADT or CADT with leuprolide acetate alone for another 36 months. The primary study endpoint was time to PSA progression (i.e., three consecutive increasing PSA values, all ≥ 4 ng/ml and ≥ 2 weeks apart). Patients were subsequently followed at 6-month intervals for a further 18 months to assess overall survival (OS).

Here are the study findings:

• 701 of the original 933 patients had a PSA level of ≤ 1 ng/ml after the initial induction regimen and were randomized to either IADT or CADT.
  • 408/701 patients (58 percent) had locally advanced prostate cancer.
  • 293/701 patients (42 percent) had relapsing M0 prostate cancer.
  • The CADT and IADT groups were comparable at baseline.
• The average (median) number of injections of leuprolide acetate administered during the 36-month randomized treatment phase was
  • 12 in the CADT group (range, 1 to 12)
  • 3 in the IADT group (range 1 to 10)
• Time to PSA progression was not significantly different between the two groups.
• Estimated 3-year PSA progression rates were
  • 10.6 percent in the CADT group
  • 10.1 percent in the IADT group
• There were no statistically significant differences between the two groups for
  • PSA progression-free survival
  • Average (mean) PSA levels over time
  • Quality of life
  • Overall survival
• Estimated 5-year overall survival rates were
  • 85.0 percent in the CADT group
  • 81.8 percent in the IADT group
• 330/352 patients (93.8 percent) in the CADT group maintained testosterone levels < 50 ng/dl throughout treatment.
• Most adverse events were mild or moderate.
• The most common adverse events were
  • Hot flushes (19 percent in the CADT group vs. 21 percent in the IADT group)
  • Hypertension (13 percent in the CADT group vs. 11 percent in the IADT group)

Schulman et al. conclude that IADT and CADT exhibited similar levels of efficacy, tolerability, and patient-reported quality of life and that IADT “may be a valid option” for selected patients with locally advanced or relapsing M0 prostate cancer.

The key defining factors in this trial are that:

• All patients were treated over time with the same types of ADT.
• To be eligible for enrollment in the randomized component of the trial all patients had to have a PSA level ≤ 1 ng/ml after the initial induction regimen.
• The trial was limited to non-metastatic, hormone-naive prostate cancer patients.

What the abstract does not tell us is

• The ages or the clinical characteristics of the patients prior to initiation of ADT (e.g., PSA levels; PSA doubling times; Gleason scores; etc.)
• What proportion of the patients had had radiation therapy vs. surgery vs. both surgery and radiation therapy prior to initiation of ADT

What the abstract does appear to tell us is that in the cohort of patients who initially responded well to 6 months of ADT induction therapy, IADT seems to have been as effective (and safe) as CADT at up to about 5 years of follow-up.

Filed under: Living with Prostate Cancer, Management, Treatment | Tagged: ADT, androgen, continuous, deprivation, intermittent, outcome |