SAN DIEGO—For women with ductal carcinoma in situ, it may be possible to deliver chemotherapy intraductally, thus providing a less toxic means of treatment, according to a feasibility study spearheaded by Susan Love, MD, of UCLA’s David Geffen School of Medicine. Dr. Love presented her research at the 2008 American Association for Cancer Research annual meeting (abstract LB-245).
“Having access to where cancer begins has great potential,” Dr. Love said. “This includes screening for markers in fluid and/or exfoliated cells, monitoring of risk, and intraductal prevention and treatment.” The research was done in conjunction with Chinese investigators from the Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing.
“The study was performed in China, where the standard of care includes a long preoperative hospital stay prior to mastectomy, which provided an opportunity for us to conduct this kind of study,” she explained.
The study included 31 women scheduled for mastectomy. Two drugs, pegylated liposomal doxorubicin (Doxil) (PLD) and carboplatin, were administered at three dose levels, with the highest dose (PLD 50 mg, carboplatin 300 mg) approximating the clinical intravenous dose. Two to 7 days prior to mastectomy, with the patient under local anesthesia, ducts to be treated were marked with dye, and the drugs were infused.
15 minutes to cannulate
In just 15 minutes, the investigators were able to consistently cannulate five to eight ducts with minimal discomfort to the patient. “The only adverse event related to the procedure was mild to moderate short-lived pain on initial instillation, ie, opening of the duct,” Dr. Love reported. Chemotherapy-related adverse events included mild nausea and vomiting after high-dose carboplatin, and erythema and tenderness after high-dose PLD.
Pharmacokinetic analyses showed that carboplatin entered the systemic circulation rapidly, which produced an early peak concentration and a short dwell time in the ducts. The area under the curve was consistent with expectations.
PLD had a delayed peak systemic concentration occurring 2 days post delivery. The peak concentration was about 20% of the expected concentration with intravenous delivery.
On pathologic exam, there was wide distribution of the drugs throughout the ductal system along with epithelial cell loss. Dye distribution showed that the drugs were successfully delivered in or near the cancer sites, although their effect on cancer cells could not be determined.
Dr. Love noted that she is a founder, board member and consultant with stock options in Windy Hill Medical, which funded the study.
The study was interesting but raised a number of questions, commented Judy Garber, MD, MPH, of Dana-Farber Cancer Institute.
“Dr. Love and colleagues have shown that they can cannulate ducts in women prior to mastectomy, and deliver PLD and carboplatin to the ducts with some systemic absorption. But this demonstration leads to two questions: How feasible is this approach overall, and in what settings would this approach be useful?” she said.
Dr. Garber suggested that intraductal chemotherapy might be applicable for women with very early breast cancer detected by ductal sampling without localization by imaging, or as a means of supplemental therapy for women with chemotherapy-sensitive breast cancer for whom the benefits of systemic adjuvant therapy are not justified.
However, she questioned whether ducts can be “reliably” cannulated, and whether one can be certain that the drug is being delivered to the tumor. Any future application “will very much depend on further proof of delivery and lack of toxicity, and demonstration of the actual effect on ductal epithelium,” Dr. Garber concluded.