DR LOVE: What’s the role of rechallenging patients with docetaxel in light of the fact that cabazitaxel is also available?
DR SMITH: When the patient takes a docetaxel holiday, if they’re still clearly responding and they enjoyed a reasonable holiday off treatment, I would typically rechallenge them with docetaxel. If they have evidence of progression at the time of discontinuation, then I would certainly switch to cabazitaxel, if they’re a candidate for additional chemotherapy.
The one other thing I might add is I tend to treat nearly all patients at a lower dose of 20 mg/m2, rather than the approved dose of 25, and I think that just reflects best clinical practice from the relatively high rate of toxicity seen in the TROPIC trial.
DR LOVE: So Tom, how long do you treat?
DR BEER: I think as William pointed out, 10 cycles was the design of TAX-327. Anything less than that is the art of medicine. I try to get to 10, but I’m guided quite heavily by the patient’s clinical experience. And so as toxicity accumulates, I don’t hesitate to stop at cycle 6, 7 or 8 if I feel like their fatigue is becoming an issue and, in particular, I’m concerned about neuropathy because that tends to be a toxicity that’s slow to resolve, may not resolve, and gets in the way of subsequent therapies.
DR LOVE: So do you stop it arbitrarily at 10 cycles, or keep going until the patient’s maximally responded?
DR BEER: Typically if we’ve gotten to 10 cycles and they’re doing well, I’ll recommend a break.
DR LOVE: So Oliver, I didn’t know this, but why the eye exams for patients on cabazitaxel?
DR SARTOR: There were some visual issues reported in the TROPIC trial. And as part of the assessment that the FDA requested was to take a very careful look at ocular findings and eye exams in the prospective trials, of which there are 2, by the way. One was PROSELICA, which was mentioned, which is 20 to 25 mg/m2 in the postdocetaxel setting. But I also wanted to mention that there’s another trial called FIRSTANA, which looks at docetaxel versus cabazitaxel. And again, cabazitaxel is both 20 and 25.
DR LOVE: So William, platinums in prostate cancer?
DR OH: I studied platinums for about 10 to 15 years. I think there’s a subset of patients who are sensitive to platinum. Unfortunately satraplatin, which Oliver and Dan were involved with, failed to get FDA approval, I think probably because we didn’t identify the subset of patients who are most likely to benefit from satraplatin. We are actually currently doing a satraplatin-directed clinical trial, where we’re doing biopsies on the patients first and then trying to create a signature, a genetic signature that would predict response based on a hypothesis I have about BRCA-ness and sensitivity to platinums.
DR LOVE: So Susan, should docetaxel be given earlier in order to get the survival benefit before the patient gets too sick to tolerate chemo?
DR SLOVIN: I think part of our problem is patients don’t want the darn chemo ahead of time. They all want to remain on pills. They all want to avoid losing their hair. And they all want to be able to travel and go places. So while I can recommend it — I mean, there have been several studies looking at docetaxel in the very early biochemically relapsed population, didn’t seem to impact on any parameters, per se. So while we could feel free to recommend chemo at any time along the continuum of prostate cancer, most patients are unwilling to go forward.
DR LOVE: So Mario, in quote, “In breast cancer we don’t use chemo and hormones at the same time, because the hormones retard the chemo effect.” Why do we do it in prostate cancer?
DR EISENBERGER: It’s a sequence. There’s a natural history here. When patients are castrated and they progress and then they use chemotherapy, I think that, while we don’t know for sure, given the current knowledge about androgen receptor signaling in general, hormonal therapy is not stopped.