Specifically, when patients had a tumor confined to one side, the physicians delivered the whole chemotherapy dose through the carotid artery on that side. However, Dr. Rasch’s team decided that if a patient’s tumor crossed the midline, they would split the chemotherapy dose in half, delivering 50% through each carotid artery.
Explore This IssueMarch 2007
Theoretically that could have led to undertreatment of the bulk of the disease, said Dr. Robbins, who discussed Dr. Rasch’s study during the ASTRO plenary session. First, most of these tumors would not be distributed equally on the two sides of the midline. Second, even for tumors that have a significant portion of their bulk across the midline from their point of origin, most of their blood supply will continue to come from the artery on the side where the disease originated.
A post-hoc subset analysis of patients in the trial may support that theory. Our analysis is not complete, but early results suggest that patients with a lateralized tumor and given unilateral infusions had better results, Dr. Robbins said. The interpretation of that observation is complicated, though, by the fact that unilateral tumors also tend to be smaller in volume than bilateral ones. And because tumor volume is known to affect the success of treatment in head and neck cancer, it is not immediately apparent whether the patients benefited from unilateral infusion or from smaller tumor size at the time of treatment.
In his own clinical experience, Dr. Robbins said that he treats 90% of his patients with a unilateral infusion, even if their disease has crossed the midline. Only when patients have a tumor spread nearly equally between the two sides would he use bilateral infusion. By contrast, approximately half of the patients in the Dutch trial were treated with bilateral infusion.
A number of us still believe this is a good way to treat patients, Dr. Robbins said. With that in mind, he and colleagues in the United States are currently designing a randomized controlled trial to test IA administration again. This time, however, the protocol will specify that unilateral infusion is to be used in most cases. The team will also look at tissue samples before and after treatment to determine how much drug is getting into the tissue and what effect it is having on the tumor.
In theory, IA delivery should lead to higher levels of drug in the tumor relative to IV doses. Because the drug is introduced in close proximity to the tumor, the diseased tissue is exposed to higher concentration of the agent, relative to what it would be exposed to with systemic IV delivery. Additionally, by pairing IA drug delivery with IV administration of sodium thiosulfate, which scavenges excess drug from the blood, physicians can give patients higher doses of the drug without risk of extensive side effects, as would be seen if such doses were delivered IV.