There’s no such thing as a perfect drug. Physicians know that for every treatment benefit a drug provides, there will also be side effects that must be taken into consideration. Ideally, these side effects can be controlled with careful dosing of the drug or close monitoring of the patient, such that the drug’s good side can be maximized while its potential toxic effects are minimized. But because every individual patient will respond to a given drug in a different way, that balance is easier said than done.
As such, the guidelines for dealing with common side effects of a particular drug aren’t always obvious, especially when the drug in question is new or its side effect is atypical. That was the case recently with a class of drugs called angiogenesis inhibitors, the first of which was approved in 2004 for cancer treatment. Angiogenesis inhibitors, such as bevacizumab and sorafenib, were developed to be more tolerable cancer drugs than the classic chemotherapy agents known for having several difficult side effects. But these drugs – which act by blocking the growth of new blood vessels around a tumor – presented with a potentially dangerous side effect of their own: hypertension. Studies found that anywhere from a quarter to 72 percent of patients given one of the these angiogenesis inhibitor drugs experienced elevated blood pressure, with the effect occasionally severe enough that the drug had to be stopped.
But as a cancer-fighter, these drugs have been very successful. So a panel, including two University of Chicago Medical Center physician-researchers, was convened by the National Cancer Institute to come up with recommendations for physicians eager to use angiogenesis inhibitors in cancer patients but concerned about the potential for hypertension. Led by Michael Maitland, assistant professor of medicine, and George Bakris, professor of medicine, the 13-member panel released their findings this month in the Journal of the National Cancer Institute. The purpose, the researchers said, was to reassure physicians that a promising new drug class can be safely used if certain precautions are taken.
“If carefully managed, I think these drugs are a huge move forward in our armory against cancer,” said Bakris, who directs the Medical Center Hypertensive Diseases Unit.
That a cardiologist such as Bakris was involved in a discussion of how to best use a cancer drug reflects the broad approach taken by the panel. Cancer drugs are most often prescribed by – you guessed it – cancer specialists, for whom hypertension is generally not a primary concern. By bringing oncologists and cardologists to the table together, Maitland said that the panel was able to come up with guidelines that satisfied both specialties and made sure the patient was being treated for both diseases. As a result, physicians can feel more comfortable treating treating patients with angiogenesis inhibitors even if they have a history of hypertension, or are at elevated risk for high blood pressure due to age, family history or diet.
“Often the case is those patients aren’t seeking medical attention for hypertension until they find that they have a tumor and need treatment for cancer,” Maitland said. “If a patient is hypertensive, a physician should not dismiss that as irrelevant just because they have advanced cancer. We already know that ignoring co-morbidities in a cancer patient can generate as much risk for their long term survival as the stage of the cancer.”
In some cases, that means cancer patients with pre-existing hypertension will have to delay the start of treatment with an angiogenesis inhibitor until their high blood pressure is brought back to a safe range. The panel recommends that doctors lower a patient’s blood pressure below the traditional ceiling of 140/90 mmHg before starting drug treatment – with even lower levels advisable for patients with diabetes or kidney disease. While many patients will understandably be anxious to start cancer treatment as quickly as possible, such precautions will reduce the chance of severe side effects such as heart attack or stroke, the researchers said.
“We’re not trying to keep anybody from getting these drugs, but there should be different levels of intensity and attention to the potential side effects based on what we know about hypertension and cardiovascular disease,” Maitland said.
The new guidelines should serve clinicians well as scientists continue to look for the exact mechanism by which blocking angiogenesis leads to hypertension and seek biomarkers that predict the severity of side effects in patients. Understanding those processes will help physicians individualize the type and dose of angiogenesis inhibitor given to each patient, further reducing toxicity and broadening the patient pool eligible to be helped by the drugs.
“Those studies are not going to change therapy, but based on what they find, they may be able to perfect therapy and make it better,” Bakris said. “This drug class has great potential for altering the natural history of many cancers. With this guidance, all physicians involved in the care of a cancer patient will be aware of monitoring blood pressure and signs of kidney injury and will know what to do if such problems arise.”
Maitland ML, Bakris GL, Black HR, Chen HX, Durand JB, Elliott WJ, Ivy SP, Leier CV, Lindenfeld J, Liu G, Remick SC, Steingart R, Tang WH, & Cardiovascular Toxicities Panel, Convened by the Angiogenesis Task Force of the National Cancer Institute Investigational Drug Steering Committee (2010). Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. Journal of the National Cancer Institute, 102 (9), 596-604 PMID: 20351338