Preliminary findings from a study with sunitinib reported at the ASCO Annual Meeting 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, said the researchers, part of the NCI-supported AIDS Malignancy Consortium.
The lead investigator, John F. Deeken, MD, a medical oncologist at Georgetown Lombardi Comprehensive Cancer Center, said in a news release that 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,” he said.
“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.”
For reasons still unclear, cancers that are unrelated to HIV infection are growing at an alarming rate in these patients, compared with the general HIV-negative population, he noted. These non-AIDS-defining cancers are also more aggressive, occur at younger ages, have higher rates of relapse, and result in poorer outcomes. For example, HIV patients are 13 to 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.
“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,” Dr. Deeken said.
The study, included in ASCO's first-ever Trials in Progress Poster Session, is testing the safety of sunitinib and has enrolled HIV patients into two groups: Those using non-nuceleotide analog reverse transcription inhibitors in their drug cocktail; and those using ritonavir-based protease inhibitor cocktail therapy.
The news release explains that the Consortium 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 NCI's Division of Cancer Treatment and Diagnosis under a Clinical Trials Agreement with Pfizer for sunitinib.
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, Dr. Deeken said.
Early findings from the nine patients enrolled to date indicate that the patients in the first group are tolerating standard sunitinib therapy, he reported. 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 that 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 have access to clinical trials of the newest agents,” Dr. Deeken said.
The AIDS Malignancy Clinical Trials Consortium, which includes approximately 37 clinical trials sites worldwide, is an NCI-supported clinical trials group funded in 1995 to support innovative trials for AIDS-related cancers. Sites that have enrolled patients in this NCI-funded study include Georgetown, Beth Israel/Deaconess Medical Center, the University of Pennsylvania, Virginia Mason Medical Center, and Washington University in St. Louis.