One of the small number of major prostate cancer presentations at the ASCO meeting this year comes from the so-called PRINCE trial of intermittent chemotherapy in men with castration-resistant prostate cancer (CRPC).
The PRINCE trial (see abstract no. 5005) was a relatively small, randomized, Phase III trial of intermittent docetaxel as compared to continuous docetaxel chemotherapy in men with CRPC. The patients received either
- Continuous docetaxel treatment until discontinuation, with docetaxel being given once weekly at a dose of 35 mg/m2 or once every 3 weeks at 75 mg/m2 or
- Intermittent docetaxel treatment with one or other of the same two doses.
In the intermittent therapy arm, patients were treated for just one study sequence of 12 weeks and then treatment was paused until clinical disease progression, defined by any one of the following: an increase in serum PSA to > 4 ng/ml with a 50% increase over baseline level, radiological progression, or symptomatic progression.
The primary study endpoint was 1-year survival, and the goal was to see whether intermittent therapy had a comparable survival benefit to continuous therapy (a so-called “non-inferiority” trial).
Yesterday morning at the ASCO meeting, Cash et al. reported the following results:
- The trial initially enrolled 187 patients, of whom 156 were eligible for evaluation (with 78 evaluable patients in each of the two arms).
- One-year survival rates were
- 72.6 percent in the continuous therapy arm
- 75.8 percent in the intermittent therapy arm
- Average (median) overall survival times were
- 18.3 months in the continuous therapy arm
- 19.3 months in the intermittent therapy arm
- The intermittent treatment met the non-inferiority criteria in 1-year survival but not for overall survival.
- The differences in progression-free survival and time to treatment failure between patients in the two arms were not significant.
- The average (median) time off treatment (“treatment holiday”) in the intermittent arm was 15 weeks (range, 1 to 69 weeks), which was equivalent to 38 percent of the overall treatment duration.
- Safety profiles of both study arms were comparable.
Cash et al. concluded that, in this study, intermittent docetaxel chemotherapy
- Was non-inferior to a continuous therapy with regard to 1-year survival
- Was well tolerated
- May present a new treatment option for patients with CRPC
It does need to be pointed out that this is a small trial that used two different dosing levels for the docetaxel. It would be interesting to see this trial repeated with a larger number of patients in a more rigorous trial using just one of the two dosing schedules to see if the results hold up in such a trial.
As an aside, one highly experienced medical oncologist told your sitemaster at the meeting that he now believes that the men who are going to respond well to docetaxel-based chemotherapy tend to start do so within 5 to 6 weeks of initiation of treatment, which may correlate well with the findings of the PRINCE study.
Filed under: Living with Prostate Cancer, Management, Treatment | Tagged: chemotherapy, continuous, docetaxel, intermittent, outcome |
THE "NEW" PROSTATE CANCER INFOLINK 
Could you clarify what this means: “that the men who are going to respond well to docetaxel-based chemotherapy tend to start do so within 5 to 6 weeks of initiation of treatment, which may correlate well with the findings of the PRINCE study.”
Thanks
Dear Steve:
It means that patients who are going to do well on docetaxel-based chemotherapy are likely to show signs and signals of good response (like a significant decline in their PSA level) within the first 5-6 weeks of starting the chemotherapy.
My impression is that in the US, the standard of care is infusions once every 3 weeks repeated 6 times = 18 weeks in total. I’ve never heard of it being given continuously in the US. Perhaps continuous treatment or 12 week cycles are used in Germany.
Allen:
I think you are misunderstanding the use of the term “continuously”. “Continuous” docetaxel chemotherapy usually means multiple cycles of chemotherapy. Each of those cycles can be given as either 75 mg/m2 every 3 weeks for a total of 18 weeks or they can be given as 35 mg/m2 each week for about 18 weeks. One then takes a short break and starts again.
By contrast, this study was designed to give either the standard dosing pattern as described above OR just 12 weeks of chemo using either of the above dosing patterns and then stop if one was in the intermittent arm until the patients’ PSA started to rise again according to a predetermined set of parameters.
In other words, no chemo is truly “continuous” in the sense that one never stops, but the form of intermittent chemo described here meant that patients could receive a much shorter initial dose of chemo and then (for the patients in whom it worked well) might be off chemo for several/many months until a repeat cycle was needed. If my memory serves from the presentation, there were some patients who had four 12-week cycles of intermittent chemotherapy in the trial, and plenty who received either two or three.
While 3 weeks does appear to be the standard of care, I am aware of patients receiving docetaxel on 2 week cycles — I forget the precise dosage but want to say 55 or 60 — and there has been recent discussion of weekly cycles on Inspire.
The major problem with the shorter cycles is that the patient never enjoys any recovery time, although the side effects may be lessened.