Excitement In Prostate and Pancreatic Cancer

Abiraterone for Advanced Prostate Caner

Castration has for long been a standard approach to treatment of men with advanced prostrate cancer. Orchiectomy and androgen deprivation with agents such as the luteinizing hormone-releasing hormone agonist drugs (e.g. Lupron) and anti-androgens (e.g Casodex) have predictable acitivity to block the effects of testosterone and/or to reduce the amount of testosterone synthesis. Inevitably, however, men with metastatic castration-resistant prostate cancer (CPRC), eventually have disease progression despite the very low levels of testosterone that such treatments induce.

A possible reason for this progression is that prostate cancer cells in these patients may have higher numbers of testosterone receptors and, therefore, are stimulated to multiply even in the presence of low testosterone in the body.

Until now, the options for treatment of CPRC patients have included second line hormonal interventions (which have not been shown to improve survival), docetaxel (Taxotere) chemotherapy, Provenge (sipuleucel-T) immunotherapy and Jevtana (cabazitaxel--a chemotherapy drug approved in 2010).

Based on a four month median survival benefit observed in a recently published pivotal clinical trial (http://www.nejm.org/doi/full/10.1056/NEJMoa1014618) , the FDA in late April approved the combination of abiraterone (Zytiga) and prednisone for men with metastatic CPRC who are no longer responding to docetaxel chemotherapy .

Abiraterone is an inhibitor of cytochrome P450 17A1 (CYP17A1), an enzyme that is involved in the conversion of cholesterol to testosterone and synthesis of other hormones, and which appears to be overexpressed in prostate cancer cells.

In the multicenter clinical trial 1195 patients were randomized to either the combination of once-daily abiraterone plus prednisone, or the combination of placebo plus prednisone. Median overall survival (OS) was 14.8 months in the abiraterone group, versus 10. 9 months in the control group. The increase in median OS in abiraterone-treated patients was statistically significant. Abiraterone was shown to be a safe drug, and relatively few serious adverse events were observed in the abiraterone arm of the trial. Since abiraterone is an oral drug, this provides a significant advantage as well.

Patients who were treated previously with the antifungal, ketoconazole, were excluded from this trial, so it is possible that such patients may experience lower responses than ketoconazole-naïve patients.

For men with metastatic CPRC who failed docetaxel treatment, Zytiga (abiraterone acetate) represents an exciting and safe therapeutic option that results in improved survival. The possibility that abiraterone could assume a front line status is being tested in an on going Phase III trial in men with metastatic CRPC who have not yet received docetaxel treatment.

Copyright 2011 A. Richard Adrouny, M.D., F.A.C.P.

Improved Survival in Pancreatic Cancer

Pancreatic cancer affects many people (it is the fourth leading cause of cancer death in the United States) and unfortunately advanced pancreatic cancer generally has a terrible prognosis. The quest for treatment regimens providing survival benefit and/or improved quality of life (QOL) is ever present. Until recently, gemcitabine (Gemzar) alone or in combination with other drugs has been considered a front line approach.

Recently the French investigator Conroy and colleagues published the results of a randomized, multicenter Phase 2-3 clinical trial comparing treatment with either the 4-drug regimen, FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and leucovorin) or single agent gemicitabine in 342 patients with metastatic pancreatic cancer and good performance status (http://www.nejm.org/doi/full/10.1056/NEJMoa1011923) .

Median overall survival for FOLFIRINOX-treated patients was improved by nearly 5 months to 11.1 months versus 6.8 months for gemcitabine-treated patients. The one year survival for the FOLFIRINOX patients was nearly 50% as compared to only 20% in the gemcitabine group. Moreover, FOLFIRINOX therapy resulted in statistically significant improvements in progression-free survival and objective response rates. Therefore, FOLFIRINOX-treated patients exhibited notable survival advantages, as compared with gemcitabine-treated patients.

The FOLFIRINOX-treated group, however, experienced significantly more adverse events. In most categories of toxicity, both hematologic and non-hematologic, the FOLFIRINOX patients fared less well than the gemcitabine-treated group. Nevertheless, at 6 months of treatment, patients in the FOLFIRINOX group had a decline in quality of life that was only half that of the gemcitabine group (31% vs 66%).

Thus for patients with metastatic pancreatic cancer who have good performance status FOLFIRINOX represents a first-line, chemotherapeutic option that may provide extended survival and improved QOL.

Shrinking the Swollen Leg

Shrinking the Swollen Leg

One of the most vexing problems for patient and physician alike is the persistently swollen leg that sometimes occurs after a blood clot. This is sometimes referred to as chronic venous insufficiency or post-phlebitic syndrome.

This basically occurs because the leg veins have valves that become stiffer and less compliant after the inflammatory process of a blood clot has subsided. Persistent clots that scar and never quite go away also contribute to the process. As a result, blood that is attempting to return from the feet and leg has difficulty making it through the damaged vein valves back to the heart and tends to reflux (pool) in the leg, causing unsightly skin changes and uncomfortable chronic swelling of the leg. This can lead to further complications, such as ulcers and varicose veins on the skin of the legs.

An article recently appeared in the New England Journal of Medicine reviewing this subject. The authors, Drs. Seshadri Raju and Peter Neglen, gave an update on the subject and reviewed evaluation and treatment of this problem

The physical examination by a physician can give a pretty good idea of what is going on, but imaging of the veins with venography is the gold standard in terms of finding out where the blocked sites are. In particular, the iliac veins (located in the lower abdomen and pelvis) are often involved, and need to be visualized.

Treatment for chronic venous insufficiency first and foremost involves graduated compression with stockings. Low pressure stockings can help control edema (swelling) but higher compression stockings, with pressures of 35 mm Hg or higher are needed to prevent things like ulcers and stasis dermatitis. Lifelong compression is recommended for a person who has had an ulcer.

Drug therapy with pentoxifylline may provide modest benefits.

Laser therapy and sclerosing therapy my help in ablating unsightly or uncomfortable varicose veins or “spiders”. Radiofrequency ablation (RFA) may also helping in place of “stripping” procedures. Other techniques, such as stenting and valve reconstruction may be useful, especially in re-opening blocked iliac veins.

The treatment of chronic venous insufficiency has developed much in recent years, almost becoming a specialty of its own. When confronted with this problem, it is wise to consult with physicians who have a special expertise in its management, including vascular surgeons, interventional radiologists and hematologists.

p.s. Due to other distractions this is my first post in quite some time and I intend to be more regular with the blog in the future. Thank you for your interest.

Introducing Thick As Blood (and Thin, Too)

Hello World. My name is Dr. A. Richard Adrouny. I am a physician specializing in hematology and oncology. I have been in practice for the past 24 years. I specialize in treating people who have cancer and blood disorders.

As the years have gone on, I have become impressed with how important the clotting system is to our health, and how important a problem clotting and bleeding problems are in clinical medicine.

I have taken a professional interest in this subject, and I host a blog called Adrouny's HEME-O-GRAM for my professional colleagues.

I have long wanted to create a website and a blog for the public, that would act as a resource for people interested in knowing more about their clotting or bleeding problems.

Over time, I intend to build a website that will be a stand alone resource for up to date information on clotting and bleeding disorders.

I will also use this blog to post new information that I read or hear about from professional medical journals or meetings that I attend.

I hope that you will find my website and blog useful.

I look forward to your comments!