Important News About Avastin in Treatment of Nosebleeds
Important News About Avastin in Treatment of NosebleedsDr. James Gossage HHT Foundation, Medical Director
There is a lot of “buzz” about Avastin in the HHT community during the past year or two. Avastin is the trade name for bevacizumab. Bevacizumab is an antibody that can attach to a protein called vascular endothelial growth factor (VEGF). VEGF is involved in the growth of both normal and abnormal blood vessels throughout the body and is increased in the blood of patients with HHT. Some people believe that increased levels of VEGF in the blood of HHT patients may be responsible for the development of telangiectasias and arteriovenous malformations (AVM), but this has not yet been proven. When bevacizumab attaches to VEGF, it blocks the actions of VEGF and theoretically decreases blood vessel growth. Interestingly, Bevacizumab was developed to treat cancer by decreasing the blood supply to growing tumors. It has been effective in the treatment of several cancers when given as an intravenous infusion. During the last several years it has also been shown to be effective in the treatment of certain non-cancerous diseases of the eyes when given as an injection into the eye.
There are so far only a few published reports on the use of bevacizumab in the treatment of HHT. The first report was published in 2006 by Flieger (pub med link 1). This report described a patient with HHT and intestinal bleeding who was treated with bevacizumab for a malignant tumor. Treatment with bevacizumab stabilized his cancer and also markedly improved his anemia and reduced his need for blood transfusion. In 2008, Mitchell and colleagues reported a HHT patient who had improvement in heart failure due to liver AVM after treatment with bevacizumab (pub med link 2). The most extensive study of bevacizumab in HHT came from the HHT Center in San Diego by Dr. Simonds and Davidson (pub med link 3). In this report, 10 patients with HHT related nosebleeds received injection of low dose bevacizumab underneath the delicate tissue inside the nose along with laser treatment. When compared to other patients from the past who had received only laser treatments by the same surgeon (Dr. Terry Davidson), the patients who received bevacizumab + laser showed a modest improvement in frequency of nosebleeds, need for blood transfusions, and quality of life. The most recent study reported on an impressive improvement in nosebleeds after the use of a low dose bevacizumab nose spray in a single HHT patient (pub med link 4). Nosebleeds almost completely stopped after a 1-2 week course of bevacizumab. Although the nosebleeds typically returned after 3-6 months, repeat courses of bevacizumab were effective. There have also been sporadic reports by word of mouth about a patient here or there who received intravenous bevacizumab for various complications of HHT (including intestinal bleeding) and had improvement, but most of these have not been published in scientific journals yet.
These reports are very encouraging and have stimulated much interest amongst patients and doctors. However, these reports are only early steps in the process of evaluating the role of this powerful medication in the treatment of HHT. Most importantly, none of these studies included a group of patients who received a placebo treatment (“placebo-controlled”), so it is not possible to say that bevacizumab was proven to be effective and safe. In general, most physicians believe that only a placebo-controlled study can prove a treatment’s effectiveness and safety. There have been many studies in the medical literature that showed promise in early stages, but were later proven ineffective when larger placebo-controlled studies were done.
Bevacizumab has also been associated with a number of side effects, but mainly during intravenous infusion of higher doses. In the cancer studies, bevacizumab had more serious side effects including life threatening hemorrhage, strokes, hypertension, and protein in the urine. However, the patients in the cancer studies received repeated intravenous infusions of moderately higher doses compared with single nasal injections in Dr. Simond’s study. In Dr. Simond’s study, 40% of the patients who received bevacizumab injections developed a hole in the membrane that separates the nasal passages. The authors have since modified their treatment and there have been no significant complications in the last 30 or 40 patients. Furthermore, patients who received low doses in the eye studies had very few side effects.
Because of potentially serious side effects and some uncertainty as to its benefit, most HHT physicians currently recommend against the routine use of bevacizumab - rather, we believe it should be reserved for use in well controlled research studies or for patients who have failed more conventional therapies.
The HHT Foundation is very interested in promoting research on the use of bevacizumab in patients with HHT. The HHT North American Therapeutics Group is currently designing a multicentered study of various treatments for HHT related nosebleeds. This will be a carefully designed study that will include a placebo group and will attempt to determine the effectiveness and safety of several different treatments for nosebleeds. Bevacizumab is one of the agents being considered for this study. It is hoped that this study will start enrolling patients in June 2010. This study will require a significant investment of money and effort by patients, clinicians, and the HHT Foundation. If you are interested in making a donation toward this very important research study, please click here. If you are interested in participating in this or other HHT research, please see the list of active HHT research by clicking here.
James R Gossage
Medical Director, HHT Foundation