Lutetium 177 (also known as Lu-177 or 177-Lu) is a very popular radioactive particle used to treat prostate cancer in Europe, as it has previously been shown to be effective against metastatic prostate cancer. For more than 10 years, Weill Cornell Medicine has been one of very few centers in the United States that is able to offer this as a targeted prostate cancer treatment.
Lutetium 177 is a radioactive material that has a short-range, which means that it can act in a targeted fashion against cancer cells with little “collateral” damage to nearby organs and tissues. It needs some help to get to these specific cancer cells though, so we combine it with the J591 monoclonal antibody that binds to a protein expressed on nearly all prostate cancer cells, PSMA. Together, this treatment compound is called 177Lu-J591.
Here’s an overview of how we use monoclonal antibodies to target cancer cells, in this case the target is the prostate cancer tumors:
The treatment approach is called radioimmunotherapy because we’re using a tiny tag of radioactive material that can kill prostate cancer cells (in this case 177Lu) and attaching it to a very specific immune-based courier (J591) to help it get inside these cells.
We already know that 177Lu-J591 can be very effective at eradicating metastatic prostate cancer cells throughout the body. In 2013, we published results from a phase II clinical trial showing that a large, single-dose of this radioimmunotherapy could be safely delivered to patients and that those patients receiving a larger dose had better response and overall survival. This is what’s called a “dose-response.”
While higher doses of 177Lu-J591 are more effective at eradicating the prostate cancer cells, higher doses also increase the likelihood of side effects, including drops in the white blood cell and platelet counts in the blood.
Building on the results of this trial and additional scientific evidence, we hypothesized that by splitting the radiation dose and giving half at the first visit and half two weeks later (a process termed “dose fractionation”) that we would be able to deliver a higher dose of the treatment while minimizing the risk of these side effects.
Today at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Scott Tagawa presented final results utilizing this split-dosed approach.
The clinical trial showed that the most effective split-dose of 177Lu-J591 was 45 mCi/m2 given in two sessions, two weeks apart, a dose 28% higher than was achievable with a large single-dose. Nearly 90% of the patients in this group experienced a decline in PSA levels, resulting in an average overall survival of more than four years. In addition, the number of circulating tumor cells (also known as CTCs or prostate cancer cells floating in the blood) was decreased or controlled by treatment. In addition to this study, the lower effect of fractionated therapy on blood counts has allowed combination of this therapy with chemotherapy.
This research was supported by the Department of Defense, Prostate Cancer Foundation and the National Institutes of Health.