Washington, DC Preliminary findings from a unique study with sunitinib suggest that it might be possible to tweak the dosage of chemotherapy drugs used to treat HIV-positive cancer patients to achieve therapeutic benefit. Given the type of drug cocktail patients use to treat their HIV, much more or considerably less chemotherapy may be warranted, say the researchers, part of the NCI-supported AIDS Malignancy Consortium (AMC). The trial design is being presented at the 2010 annual meeting of the American Society of Clinical Oncology (ASCO).
Researchers say the early analysis is important because it highlights the Catch 22 that many HIV-infected cancer patients face. "Cancer unrelated to AIDS is rapidly increasing in HIV-positive patients, yet many oncologists do not know how to treat these cancers, and these patients are also excluded from cancer clinical trials," says the study's lead investigator, John F. Deeken, M.D., a medical oncologist at Georgetown Lombardi Comprehensive Cancer Center.
"While such caution is understandable, it may be scientifically unjustified as well as fundamentally unfair, and this study is designed to help guide treatment for these patients," says Deeken, who will present updated data on June 7 during the Trials in Progress Poster Session ASCO.
For reasons that are unclear, cancers that are unrelated to HIV infection are growing at an alarming rate in these patients, compared to the general HIV-negative population, he says. These non-AIDS-defining cancers are also more aggressive, occur at younger ages, have higher rates of relapse and poorer outcomes, Deeken says. 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 developing lung or head and neck cancers, he says.
"A key challenge in treating these patients is that anti-HIV medicines are notorious for causing drug-drug interactions. Such interactions with anti-cancer chemotherapy drugs could lead to serious side effects and toxicities in patients," Deeken says.
This study is testing the safety of the chemotherapy drug sunitinib (Sutent) and has enrolled patients into two groups of HIV patients group 1: those using non-nuceleotide analog reverse transcription inhibitors (NNRTIs) in their drug cocktail and group 2: patients using ritonavir-based protease inhibitor cocktail therapy.
The AMC chose to study sunitinib because this oral medication was approved to treat kidney cancer, which is occurring at a higher rate among HIV patients, and is being studied in other cancer types that also affect these patients, such as lung and colorectal. The study is being sponsored by the Division of Cancer Treatment and Diagnosis, National Cancer Institute under a Clinical Trials Agreement with Pfizer, Inc for sunitinib.
Like many cancer drugs, sunitinib is a "prodrug" that requires the CYP450 family of enzymes in the liver to activate the drug for it to be effective. The drugs used in the first group are not known to inhibit the liver enzymes but agents used in the second group are known to inhibit enzyme activity, which means that cancer drugs that also use these enzymes could become too potent and therefore toxic, Deeken says.
Early findings from the nine patients enrolled to date indicate that the patients in the first group are tolerating standard sunitinib therapy. In fact, the HIV cocktail used by some in the first group may be inducing liver enzyme activity which suggests that higher doses of sunitinib might be warranted in these patients. It also appears that a low dose of sunitinib in the second group of patients is being highly activated, implying these patients could benefit from an even lower dose of chemotherapy.
The study will test the effects of different doses of sunitinib in participants, watching for toxicity as well as effectiveness.
"These are early days, but we hope the information we learn from this study will help these cancer patients get the therapy they want and need, as well as access to clinical trials of the newest agents," Deeken says.
|Contact: Karen Mallet|
Georgetown University Medical Center