The patients who have grade II or grade III disease
Now what about the patients who have grade II or grade III disease? These patients were randomized to either observation or cisplatin as a single agent. The disease-free survival at five years for the cisplatin group was 83%, for the observation group was 64%. That’s highly statistically significant. The overall survival at five years was 87% versus 81%. Better with cisplatin than with observation, but not statistically significant. Now some people accept disease free survival improvement as a reason for treating, others don’t. My own opinion is that these patients ought to be treated with some form of platinum based therapy because of the difference that we see in the disease-free survival. But there is still an ongoing debate about this group.
The other group, those at high risk, because of other factors, were randomized to either intraperitoneal P32, which was a nice placebo, or cisplatin based therapy. Actually when this study was started this was considered the standard but we have reasonable evidence to suggest that it really has very little impact. At five years the patients who got cisplatin had an 81% disease-free survival compared to 66% with intraperitoneal P32 and there have been too few events in the overall survival at five years to permit any kind of reasonable analysis, but there is a small difference favoring the cisplatin based therapy. Again, the same reasoning applies here. Either you accept disease free survival improvement as a reason for treating or not. The consensus among the gynecological oncology community at least is shown on this side. That is, that everybody ought to have a hysterectomy, a bilateral salpingo-oophorectomy and a careful surgical exploration to document the exact stage of disease. Those deemed to be at low risk for recurrence, the low risk group, should receive no further therapy. And those deemed to be at high risk either because of grade or because of one of the other factors, should receive some form of platinum based therapy with expected improvement in disease free survival to 82% at five years as compared to 60% with not treatment. If I were picking the therapy I would use a combination of Taxol and platinum in this group but we have no studies as yet showing that that has any advantage over single agent cisplatin.
Now what do we do in the salvage setting? There’s actually on the ASCO site a summary of a lot of data on salvage therapy if you are interested. It’s in the section on the educational material from the 2006 meeting. But very briefly, what we are talking about here is a population of patients who either recur after or progress on front line therapy. And the general principle or approach to these patients is to look at what their response was to front line therapy and then base your decision on that. In that regard, what you do is try to divide the patients up into two groups. A group of patients that almost certainly are still sensitive to the drugs they received as a part of front line therapy, and a group of patients who almost certainly are going to be resistant to those drugs. Those who should be considered sensitive are those who responded to front line therapy and had a significant treatment-free interval before they required further treatment. Now the current definition the cooperative groups are using is six months. There is nothing magic about six months. What that real number should be, we don’t know for sure. It’s probably a continuum. Six months has been selected as the break-point by the cooperative groups. For chemo-resistant disease; this includes those patients who either progress while receiving front line therapy or whose best response to front line therapy was stable disease, or who had a short treatment-free interval before they recurred. That is, less than six months. In those who are chemo-sensitive, they ought to be retreated with a platinum-based regimen. And if you use Taxol/platinum front line, Taxol/platinum is what ought to be used second line. The best data we have suggests that the expected response rate here is between 50-60% and the median survival will approach two years. Those patients who were resistant to front line therapy should be treated with alternative drug therapy. Now the list of drugs actually includes a total of seven.