The two regimens that are acceptable
So by 2006 our standard of care has changed in regard to the two regimens that are acceptable. I personally think that there are two regimens that are reasonable. You could add a third. The two that most people would mention would be Taxol as a 24-hour infusion at a dose of 135 per meter square followed by cisplatin at 75 per meter square, as tested in GOG111. Or Taxol 175 per meter square over three hours followed by carboplatin, dosed to an AUC of 4-5 based on the best evidence that we have. Some would add also a third arm, a 24-hour infusion of Taxol at 135 per meter square followed by carboplatin dosed to an AUC of 4-5. Those would be reasonable approaches to the treatment of ovarian carcinoma at the present time, for advanced disease.
Now let’s look briefly at limited disease, stage I or stage II disease. The way we approach this disease really is to divide the patient population into two groups; a low risk group and a high risk group. These are the current GOG definitions of these two groups; patients at low risk are those who have all of the following features: grade I disease that is intracystic in nature. That is, it is contained within the substance of the ovary, there is no tumor on the surface of the ovary, so that one way you might picture it is that the tumor does not have access to the peritoneal cavity to seed. There is no evidence of disease outside of the ovary. In other words, this is not a stage II patient. Peritoneal cytology is negative and there is no ascites. If all of these features is present that patient will be at low risk for recurrence. Patients are at high risk for recurrence if any one of these features is present: grade II or grade III disease, extracystic disease – that is, disease on the surface of the ovary so it has access to the peritoneal cavity – disease outside the ovary, stage II disease, positive peritoneal cytology or ascites. If any one of those factors is present that patient will be at high risk for recurrence and their approximate relapse rate will be 40%. Quite high. For the low risk group the approximate relapse rate will be 10%.
Now how do we manage these? Well, the best evidence we have to date comes from an Italian trial run by the GCOG group where they looked at three groups of patients. One group they labeled low risk, and uses the exact definitions that I just gave you – that is grade I disease, intracystic, no ascites, no peritoneal cytology and no extra-ovarian disease. Group number two were deemed to be at what they called intermediate risk, and this increased risk was associated with either grade II or grade III disease. That was the only reason for putting these patients into a higher risk group. And in the third group, patients were at higher risk because of one of the other factors we talked about, either ascites, positive peritoneal cytology, extra-ovarian disease or disease on the surface of the ovary. In the first of these groups, those at low risk, they simply observed these patients. They had 92 patients on study, at a median follow-up of 45 months there have been five relapses. The five year disease-free survival is 90%, the five years overall survival is 92% and with continued follow-up there have been virtually no relapses beyond this point. So it would appear that with just simple observation you are going to have a cure rate of 90% or better. For that reason our standard of care in this group of patients is no further therapy.