Dizon Discusses Advantages of IP Chemotherapy for Ovarian Cancer

Don Dizon, MD

Intraperitoneal (IP) chemotherapy offers a median 10-month survival advantage over IV chemotherapy for women with advanced ovarian cancer, according to a retrospective analysis recently published in the Journal of Clinical Oncology.

The analysis, which pooled data from two Gynecologic Oncology Group (GOG) studies (114 and 172), compared 10-year survival outcomes with IP versus IV chemotherapy in 876 women. The survival advantage translated into a 23% reduction in the risk of death (HR = 0.77; 95% CI, 0.65-0.90; P = .002). Further, the risk of death decrease by 12% for each cycle of IP chemotherapy completed (HR = 0.88; 95% CI, 0.83-0.94; P<.001).

Despite positive results such as these, IP chemotherapy is currently not widely utilized for ovarian cancer treatment, said Don Dizon, MD, Assistant in Medicine, Medical Gynecologic Oncology, Massachusetts General Hospital.

In an interview with OncLive, Dizon explains the advantages of IP therapy and why further research and education are necessary to bring it to the forefront of ovarian cancer treatment.

OncLive: What makes this analysis significant?

Dr Dizon: I think this is an important finding for us. What I found most interesting is that researchers actually came up with a mathematical figure that suggests there is an advantage gained with each cycle that is administered of IP therapy. This is new information for us.

If you look at one of the largest randomized trials, GOG-172, it showed a survival advantage with IP therapy, but a large portion of those patients were not able to complete six cycles of treatment. The question had always been, “Would there have been a larger benefit to therapy had more women completed treatment?” These findings suggest that there is a sequential, and perhaps even additive, benefit with more IP therapies administered.

I think the researchers from this study should be congratulated on the findings that IP chemotherapy extends survival now with longer follow-up. The study went to 10 years, and confirmed a nearly 5-year survival advantage compared to 4 years with IV. That is significant. This provides confirmatory data that IP really is better. While this is not the first study that showed that IP chemotherapy does improve survival, this is one of the largest with the longest follow-up. It goes beyond the question of “Is IP the right option?” to “How many cycles of IP are best?”

In those past studies, what were some common reasons why patients could not complete six cycles of IP therapy?

There are many possible reasons, including patient discomfort, port malfunction, and the challenge of placing an intraperitoneal therapy port. It does require a large volume of fluid administered into the abdomen. It could be due to toxicities related to therapy as well. If you looked at GOG-172, it is clear that neuropathic concerns lasted longer with IP therapy than it did with IV treatment. We are aware that IP is a harder thing to deliver than straight chemotherapy.

What obstacles have prevented IP therapy from being more widely used?

It takes several resources to deliver IP chemotherapy and it takes a bit more expertise to do it safely. The provider must watch the patient closely for fluid, to make sure that they are hydrated. They also must regularly check lab work to be sure the kidneys are not impacted negatively. It takes some expertise to do it. Those of us who do gynecologic oncology are fairly committed to it, but in a community practice center where you are seeing tumors of all types, it can be difficult for a center to dedicate resources to IP chemotherapy for ovarian cancer. I do not think there is a huge commitment to resources at this point.

Also, I think we need to get over the barriers perception. Many people feel that it is too toxic. We need patients to have more awareness and be informed about their options. If we could increase patient awareness about how important IP is as an option, that could push more providers to adopt it. There is no doubt that we need to find regimens that are far more tolerable and less challenging to deliver. Studies like this will help us make the argument that women with ovarian cancer should be afforded the best chance for long-terms survival. For a group of women, their best chance is with IP therapy.

Are there ways to make delivering and receiving IP therapy easier for providers and patients?

One of the things we’ve been working at is how to make it more tolerable. We are seeing if we can tailor the regimen from GOG-172 to a more practical one. In the GOG-172 regimen, a treatment is given on the first day, then there is a treatment given on the second day, and then a treatment is given on the eighth day, and that continues for 3 weeks. On the first day you give an extended infusion of paclitaxel, followed by IP therapy with cisplatin on day 2, and followed by IP paclitaxel on day 8.

We asked, “can we get away with a lower dose of cisplatin and get rid of the second day infusion?” Instead, we examined administering the first two treatments on day 1 and then the IP paclitaxel on day 8. We showed feasibility with this regimen. It was more tolerable and more cycles were completed with these modifications. Carboplatinum in IP is another being attempted. There is a lot of research out there right now.

Why does IP have a survival advantage over IV chemotherapy for ovarian cancer?

There are several theories that take into account the way ovarian cancer progresses. We know that, for most women who relapse, it happens in the abdomen and pelvis. Therefore, there may be something about the tumor environment that makes it more prone to reoccur in that area. IP therapy locally produces a higher concentration where the cancer sits. The concentration of IP is much higher than what can be achieved by IV chemotherapy.

Who is the ideal patient for IP therapy?

We know that it only works in select patients. People under 65 years old do best. People with larger tumors do not have a benefit from IP therapy. There seems to be a tumor-size threshold. We are only using this in patients that have had successful surgery, which means that they have no residual disease at the end of a surgery or up to just 10 millimeters of disease after surgery. So we are already selecting patients already based on surgical outcome and trying to really identify those patients that will benefit the most. Histology also may play a role. People with serous carcinomas are going to have a better result with IP therapy.

Tewari D, Java JJ, Salani R, et al. Long-term survival advantage and prognostic factors associated with intraperitoneal chemotherapy treatment in advanced ovarian cancer: a Gynecologic Oncology Group study [published online March 23, 2015]. J Clin Oncol. doi:10.1200/JCO.2014.55.9898.