Tag: Cancer Treatment

Aligned with Cancer Cures in Mind

Cancer CureThrough clinical trials, we are able to develop safe and more effective ways to detect, diagnose and treat cancer. All clinical trials have a sponsor, which means there is an organization or person involved in the design and support of the study. The sponsor is usually a pharmaceutical company, academic institution or government body. In the United States, there has been a fairly recent increase in the number of government-sponsored studies.

The majority of cancer clinical trials are led by the National Cancer Institute (NCI)-sponsored cooperative groups. This means that cancer specialists across hospitals, medical centers and community clinics can more easily collaborate with one another through a formalized group. One major advantage of NCI-funded cooperative group clinical trials is the ability to study diseases and/or treatments that may be less interesting or practical for pharmaceutical companies or individual academic centers.

Following a series of recommendations leading to mergers, there are now five main groups in the US that form the NCI Clinical Trials Network (NCTN). One of these main groups, the Alliance for Clinical Trials in Oncology, was formed in 2011 after the merger of Cancer and Leukemia Group B (CALGB), North Central Cancer Treatment Group (NCCTG) and the American College of Surgeons Oncology Group (ACOSOG). These mergers streamlined many research efforts that were previously happening on parallel or competing trajectories.

Weill Cornell Medicine (WCM) has investigators involved in all five of the major cooperative groups, but is most heavily involved in the leadership of the Alliance. Dr. Scott Tagawa, Medical Director of the Genitourinary (GU) Oncology Program, serves as Weill Cornell Medicine’s Principal Investigator for the Alliance and a member of the Board of Directors. Dr. John Leonard serves as Chair of the lymphoma committee and member of other leadership committees.

There are many WCM investigators currently leading studies within the Alliance group. The GU committee has a high level of involvement by our medical oncologists, Drs. Tagawa, Beltran, Molina, Nanus, and Faltas. Additionally, Dr. Barbieri and other urologists from our team have recently become more involved in the Alliance.

We have a long history of participation in the GU oncology studies through CALGB and the Alliance, most recently with completed studies in early stage prostate cancer. These include testing:

  • Dietary intervention in men with low risk disease who are on active surveillance (Clinical Trial ID: 70807)
  • Chemohormonal therapy prior to surgery in men with high risk disease (90203)
  • The addition of antiangiogenic therapy in addition to chemotherapy for advanced urothelial carcinoma (90601)
  • Testing the impact of targeted oral therapies in curbing the spread of cancer in patients with intermediate to high risk, advanced renal cell carcinoma (RCC) (A031203)

Through our cooperative groups, we are currently accruing to studies in advanced prostate cancer and early stage bladder cancer with additional new clinical trials in the works.

Prostate cancer:

Bladder cancer:

The Alliance for Clinical Trials in Oncology is committed to reducing the impact of cancer on people by uniting nearly 10,000 scientists and clinicians across the United States and Canada, from many disciplines, hospitals, medical centers and community clinics. Together we’re discovering, creating, validating and implementing new, more effective strategies to prevent and treat cancer; we’re proud to be part of it!

Dying from Prostate Cancer: Lessons Learned from the PLCO Trial

Screening for any disease, including prostate cancer remains imperfect. One study, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, was a National Cancer Institute (NCI) sponsored study that took place between 1993-2001. The goal of the trial was to investigate the impact cancer screening had on dying from these four common tumor types. There were 76,693 men evaluated in the prostate cancer portion of the study.

While some aspects of this randomized trial remain controversial, including the impact that screening had on dying from prostate cancer, it remains a rich prospective dataset for further analysis, as it is one of the largest longitudinal studies ever conducted of men with prostate cancer.

In the “intervention” arm of the PLCO Screening Trial in which men were randomized to be screened for prostate cancer with annual prostate specific antigen (PSA) blood tests and digital prostate exams, there was still an unfortunate set of men who died from prostate cancer. Because the goal of the trial was to determine the prostate cancer mortality differences between the two arms, an understanding of who died and how they died is extremely important.

In a study led by Weill Cornell Medicine’s Dr. Chris Barbieri, we examined how men died of prostate cancer. Dr. Sameer Mittal presented the results of the research at an oral podium presentation yesterday at the 2016 American Urological Association annual meeting, with full results simultaneously published in European Urology.

Of 38,340 men in the screening arm, 151 died of prostate cancer. After graphing their oncologic courses of diagnosis and treatment, we noted a few interesting trends. The most prominent were as follows:

  • More than 50% of the men who died (81 men) either were never screened before this test or had their first PSA test result that was positive. These men were older and had higher median PSA (13.7). It’s possible that if these men were actually screened and or screened earlier and treated, their deaths from prostate cancer could have been prevented.
  • A subgroup of men who died despite screening were young and had a low median PSA (2.0). Surprisingly, they died within approximately 1.5 years of diagnosis. To put this in perspective, we expect an average man diagnosed with metastatic prostate cancer to live for 5 years, so this is quite unusual. We know that some subsets of prostate cancer do not secrete high levels of PSA and this is an area that needs more research in order to prevent further deaths. We don’t know for sure if these men had neuroendocrine prostate cancer (NEPC), but their rapid disease course seems consistent with this aggressive prostate cancer sub-type.

Despite what some may believe, some men do die of prostate cancer. We continue to research why this is the case in order to prevent further death and suffering from this common disease. These study insights underscore the importance of developing diagnostic biomarkers to better detect aggressive prostate cancers and to best predict the way the cancer will respond to various treatments.

Marking their Territory: Using Cell Markers to Find Cancer and Stop its Spread

Cancer Cell Markers and AntibodyA key way to detect cancer cells in the body is to find “markers” on the cancer cells that don’t exist in healthy cells. For prostate cancer, we use a marker called the prostate specific membrane antigen (PSMA). PSMA is a protein on the cell surface of most prostate cancer cells, but it is not usually present elsewhere in the body. As a result, we’re able to use PSMA in order to track the presence of prostate cancer tumor growth and metastasis. At AACR 2016, the Weill Cornell Medicine (WCM) and Meyer Cancer Center investigators presented the results of two new studies that further hone in on the role PSMA plays in prostate cancer.

While we’ve known about the presence of PSMA for many years, we have recently discovered more about its biology and the tight relationship it has with the key driver of most prostate tumors, the androgen receptor (AR) pathway. As the AR pathway becomes more abnormal (is more dysregulated), the amount or expression of PSMA increases. This means that more aggressive tumors will have more PSMA on the cells.

How do we measure or quantify the amount of PSMA?

At the Weill Cornell Genitourinary (GU) Oncology Program, one way we do this is by using non-invasive methods to locate active tumors in prostate cancer patients. By tagging an antibody or small molecule with a particle that gives off energy, we can “see” the PSMA using imaging techniques. In this case, we can give people an injection to bring these tagged molecules into the body and then follow the “energy” the molecules are giving off with a scan that visualizes the tumors. In some cases, this approach helps us locate tumors that might otherwise be hidden.

However, we may also be able to assess the biology of tumors without a biopsy (non-invasively). To do this, we analyzed men who had undergone molecular PSMA imaging. Following infusion of the anti-PSMA monoclonal antibody J591 which was tagged with a particle, men underwent scanning. Based upon a system we previously published, we scored how bright their tumors were with the belief that brighter tumors would be more aggressive. In long-term follow up of the men who underwent imaging between 2000-2015, our hypothesis was confirmed. The men with the brighter tumors had higher rates of mortality, even among those who received the newer, better therapies. This type of non-invasive molecular imaging may assist physicians in determining prognosis, which may in turn guide therapy choices for especially aggressive cancers.

Antibodies as a Treatment Vehicle

In addition to tagging an antibody with an imaging agent, we can label J591 with a radioactive particle capable of killing the cancer cells, termed radioimmunotherapy. For more than a decade, we have delivered different versions of this therapy to patients at WCM. A phase II clinical trial published in 2013 was shown to be very successful at delivering a large, single-dose of radioimmunotherapy to patients, also showing that those patients receiving a larger dose had better response and survival (a “dose-response”). Building on the results of this trial, we hypothesized that by splitting the radiation dose and giving half initially and half two weeks later (this is called “dose fractionation”) that we would be able to ultimately deliver a higher dose of the treatment. At ASCO in 2010, we demonstrated this to be a promising approach to treatment and will be presenting a follow up expanded version of this study in June at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.

At AACR 2016, Dr. Ana Molina presented results of a pilot study of hyperfrationated (very split doses) 177Lu-J591, which delivers the radioactive particle lutetium-177 (177Lu) to tumors via the anti-PSMA monoclonal antibody J591. In this study, small doses of the radioimmunotherapy were delivered every two weeks until blood counts started to drop, as measured by the level of white blood cells and platelets. This treatment approach allowed all patients in this small study to receive a higher total dose than could be safely delivered with a large single dose. Two patients received five and six total doses of the treatment, reflecting a range 179 – 214% higher than the single large dose. As a result, this new approach to administering this type of immunotherapy with very split dosing may have long-term merit for men with advanced prostate cancers.

Today, men with advanced prostate cancer are able to benefit from a number of new treatment options, including the common oral hormonal drugs, abiraterone and enzalutamide. These hormonal drugs help decrease the burden of the cancer, maintain or improve the quality of life, and allow men to live longer. However, none of these drugs are curative, so we still need to make advancements in the field.

This is why we continue to use what we already know about cancer “markers,” such as PSMA, and to build on this knowledge in order to better diagnose and treat prostate cancers in a way that exploits these markers and keeps the cancer at bay. We are also constantly seeking new ways to better “see” and leverage these markers, and specifically PSMA, to prevent the growth and spread of prostate cancer.

Learn more about some of our current open clinical trials exploring this approach: