Schering-Plough Corp announced results from a phase III study that showed maintenance chemotherapy with pegylated liposomal doxorubicin hydrochloride (Doxil, marketed in Canada and Europe as Caelyx) significantly prolonged time to progression (TTP) in patients with metastatic breast cancer with infrequent and manageable clinical toxicity after first-line chemotherapy. These data were presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

"While standard chemotherapy has proven effective for patients with metastatic breast cancer, their response is short-lived and the time to progression is brief," said Emilio Alba, MD, professor at Hospital U. Virgen de la Victoria, in Malaga, Spain, and lead investigator for the study. "The results from this study showed a significantly improved time to progression (13.2 months) in patients treated with Caelyx vs the observational arm (10.2 months)."

The Spanish Cooperative Group, Grupo Espanol de Investigacion en Cancer de Mama (GEICAM) conducted the multicenter, phase III study at seven different sites throughout Spain. Of the 288 patients with metastatic breast cancer registered for the trial, 155 subjects who had responded to initial therapy or had stable disease were randomized either to receive liposomal doxorubicin or to observation.

Study Design and Findings

Patients receiving therapy were given a regimen of the drug at 40 mg/m²once every 4 weeks for six cycles of therapy. Patients in the doxorubicin arm experienced a median improvement in time to progression of 3 months (13.2 vs 10.2 months in the observational arm; P = .0005).

The patients enrolled in the study had a median age of 57 years, and had adequate bone marrow, renal, hepatic, and cardiac function. These patients had experienced either complete response, partial response, or had stable disease. Patients received induction chemotherapy with three cycles of an anthracycline followed by three cycles of a taxane, and were then randomly assigned to either the liposomal doxorubicin therapy or the observation arm.

The incidence of nausea/vomiting and alopecia were low and manageable; 21% of patients experienced grade 1 or 2 nausea/vomiting, and 29% experienced alopecia. Importantly, neither clinically relevant left-ventricular ejection fraction nor clinical congestive heart failure was observed.

Further Evaluation Indicated

"The study results are promising and suggest the potential value of Caelyx in the management of metastatic breast cancer," said Robert J. Spiegel, MD, chief medical officer and senior vice president, Schering-Plough Research Institute. "Further evaluation is indicated to confirm that Caelyx is effective and safe for select metastatic breast cancer patients who are at increased cardiac risk."