Righting a Wrong in Cancer Treatment

June 9, 2010

Oncologist John Deeken, MD, was a bit mystified. Four HIV-positive patients with head and neck cancer came to him for treatment, but he couldn’t find any guidance from research studies as to the best agents to use. That’s because, he discovered, HIV-positive cancer patients are, almost as a rule, excluded from cancer clinical trials.

That doesn’t make sense, he thought, because cancer unrelated to HIV/AIDS is reaching epidemic proportions in people infected with the virus.

For reasons that are unclear, non-AIDS-defining cancers are on the rise. They are also more aggressive, occur at younger ages, have higher rates of relapse and poorer outcomes, compared to the HIV-negative population. For example, HIV patients are 13-31 times more likely to develop Hodgkin’s lymphoma, they have a seven times higher rate of developing liver cancer, and three times the rate of getting lung or head and neck cancers, he says.

Deeken didn’t know those statistics then, but he does now. While attending to his patients, he learned that many physicians do not know how to treat cancers in HIV-positive patients, given that they are taking multiple medications, and that some think treatment is a waste since these patients will die of AIDS in any case. That latter concern isn’t true, of course, he says, because today’s antiretroviral drugs allow those with HIV to have a near-normal lifespan.

And while concern about drug-drug interactions in cancer treatment is understandable, it may be scientifically unjustified, Deeken says. “How would one know? There haven’t been any studies looking at this and consequently, there are no standard approaches or guidelines to treat non-AIDS related cancers in these patients,” he says.

Most of all, Deeken had the sense that it wasn’t fair that HIV-positive patients were excluded from cancer clinical trials. “Cancer patients, whether or not they have HIV, want to be part of clinical studies, to receive the newest therapies, live as long as they can, and help future patients,” he says. “We don’t put enough people on these trials in any case, and here we are excluding a whole class of people for no good reason.”

So Deeken decided to get involved. Exercising his expertise in clinical pharmacology (the science of how drugs are metabolized in the body), he did his own research and put four head-and-neck cancer patients on the chemotherapy drug cisplatin. They did well.

And Deeken helped Georgetown University and the Georgeown Lombardi Comprehensive Cancer Center join the AIDS Malignancy Consortium, a long established NCI-cooperative group that has led research into the etiology and treatment of AIDS-defining cancers such as Kaposi’s sarcoma, and is now active in investigating the causes of cancers that appear to have little to do with HIV infection. He now heads a nationwide study that is the first to test new chemotherapy drugs in HIV-positive patients who have so-called non-AIDS defining cancers.

The design of that study will be discussed in early June at the 2010 annual meeting of the American Society of Clinical Oncology in a new session designed to highlight clinical trials in progress. Preliminary findings from this clinical trial suggest that it might be possible to adjust the dosage of chemotherapy drugs used to treat HIV-positive cancer patients to achieve therapeutic benefit. Given the type of drug cocktail patients use for HIV, much more or considerably less chemotherapy may be warranted, Deeken says.

The question the team investigated is if a family of metabolizing enzymes in the liver causes cancer drugs in patients already using HIV medications to be too potent, and thus toxic, or too weak, and thus ineffective. They tested the new chemotherapy sunitinib (Sutent) but half of all cancer drugs use the same enzymes to either activate or metabolize and inactivate the agents.

Early findings suggest that patients who are treated with a cocktail of agents that use non-nuceleoside reverse transcription inhibitors (NNRTIs) to treat HIV may need more cancer chemotherapy because these liver enzymes seem to be induced and have higher activity. On the other hand, patients being treated with a Ritonavir-based protease inhibitor cocktail therapy appear to need less chemotherapy. That’s because these HIV agents block the activity of the liver enzymes, so “normal” levels of sunitinib and similar chemotherapy drugs may be too potent and cause unwanted side effects.

The study is in its early days, but progress is palpable, says Deeken. Hopefully, the findings will suggest the best doses for this and other cancer therapies in the future, and provide insight into whether one anti-HIV regimen will work better or not, he says. “This is what science does. It asks and answers questions that matter to people – whether or not they have a viral infection.”

James Dunn agrees. A resident of Washington D.C – an area hard hit by HIV - Dunn is HIV-positive and a cancer survivor. He has served with community advisory boards, including two at GUMC, and knows that people like him are kept out from the latest advances. “To exclude them is to prevent some of the most needy people from participating and benefitting from research, and that is a shame,” he says. “We are losing a wealth of knowledge and benefits to the community.”

Author: Renee Twombly, GUMC Communications