(a monoclonal antibody conjugated to doxorubicin) plus docetaxel (Taxotere) was
well tolerated in patients with metastatic breast cancer or colorectal cancer
and showed objective responses, according to a phase II trial.
Lisle M. Nabell, MD, assistant professor of
hematology/oncology, University of Alabama, Birmingham, presented the results
at a poster session of the 38th Annual Meeting of the American Society of
Clinical Oncology (abstract 55).
The linking antibody of SGN-15 (chimeric BR96-doxorubicin,
Seattle Genetics) is directed at the Lewis Y antigen. Both breast and
colorectal tumors express the antigen. The agent is rapidly internalized.
Hydrazone cleavage releases the doxorubicin intracellularly. A 200-mg dose of SGN-15 delivers 6 mg
of doxorubicin directly to the tumor cells. "It’s biological targeting
at its best, if it works," Dr. Nabell said.
Preclinical trials indicated a synergy when SGN-15 was
combined with a taxane agent. A prior phase I study of the SGN-15/docetaxel
combination encountered unacceptable gastrointestinal (GI) toxicities. But
investigators at the University of Alabama decided to try a different dosing
schedule during a phase I trial in which 16 patients received escalating doses
of SGN-15 with a fixed dose of docetaxel.
The phase II study involved two cohorts of patients with
metastatic breast cancer or metastatic colorectal cancer. The results from each
cohort were analyzed separately. "The questions were, is the GI toxicity
acceptable and is it effective," Dr. Nabell said.
Eligibility for the study included metastatic disease, Lewis
Y antigen expression, and a life expectancy of greater than 3 months. Patients
were allowed to have been previously treated with chemotherapy for their
The 18 colorectal cancer patients ranged in age from 29 to
77 years (median, 58.5). Eleven were male. The 26 breast cancer patients
evaluated to date ranged in age from 35 to 78 years (median, 53.5). One was
male. Patients received weekly SGN-15 175 mg/m2
and docetaxel 30mg/m²
for 6 weeks, followed by a 2-week rest period.
Two patients in the colorectal cohort and six in the breast
cancer cohort experienced reversible grade 3 or greater nausea and vomiting. An
asymptomatic grade 3 or greater increase in lipase levels was seen in three
colorectal patients and two breast cancer patients.
Grade 3 or greater neutropenia occurred in one colorectal
cancer patient and two breast cancer patients. There was no grade 3 or higher
diarrhea, and only one case of grade 3 or higher mucositis (in a colorectal
Investigators saw an objective response in one colorectal
cancer patient and in three breast cancer patients, including one patient with
a 70% reduction in hepatic disease. Disease stabilization was seen in four
colorectal cancer patients and 6 breast cancer patients. The breast cancer
study continues to enroll patients.
"It’s a novel compound," Dr. Nabell said. "The idea that we
could deliver a drug intracellularly is provocative. But we have to wait until
the end of the phase II study to see if it warrants further evaluation in a
phase III trial."