treatment approach that involves the administration of liposomal doxorubicin (Myocet,
investigational in the United States) and paclitaxel (Taxol), then heat
delivery to the tumor, appears to enhance the efficacy of the chemotherapy,
according to a study reported at the 38th Annual Meeting of the American
Society of Clinical Oncology (abstract 200). Lead investigator Kimberly
Blackwell, MD, a medical oncologist at Duke University Comprehensive Cancer
Center, called the results "impressive."
The phase I trial involved 21 stage IIB-III breast cancer
patients. Patients received four cycles every 3 weeks of liposomal doxorubicin
and paclitaxel, followed by 1 hour of hyperthermia via a phased array microwave
system. Doses escalated from liposomal doxorubicin 30 mg/m2
plus paclitaxel 100 mg/m2
up to 75/175 mg/m2.
While hyperthermia has long been known to boost the effects
of radiation therapy, its ability to enhance a tumor’s response to drugs
encased in liposomes is just being explored in humans.
The patients receive their chemotherapy, then are placed
face down on a table with their breast submerged in a sunken pool of water
through which microwave energy is delivered (see Figure).
The heat activates the agents, coaxing the doxorubicin out
of its liposomal coating to attack the tumor. The body’s normal tissues remain
unheated; therefore, the chemotherapy works preferentially at the tumor site
and affects normal tissue only gradually over 3 to 4 weeks, thus blunting the
"Encapsulating the chemotherapy inside of liposomes enables
us to deliver 30 times more chemotherapy to the tumor site than we normally
could, without too much toxicity," Dr. Blackwell said. "Heat also boosts the
drugs’ potency by interfering with mechanisms that control a cancer cell’s
ability to replicate."