Doxil improves TTP in breast ca

ASCO—After first-line treatment with chemotherapy for metastatic breast cancer, maintenance therapy with pegylated liposomal doxorubicin (Doxil) may significantly improve time to progression (TTP), according to a multicenter phase III study from the Spanish Cooperative group GEICAM reported at the 43rd Annual Meeting of the American Society of Clinical Oncology (abstract 1007).

"The cardiotoxic effects of anthracyclines are of concern. Liposomal doxorubicin has shown comparable efficacy to conventional anthracyclines, but less cardiotoxicity," said lead investigator Emilio Alba, MD, of the Hospital Universitario Virgen de la Victoria, Malaga, Spain.

In the GEICAM 2001-01 trial, 155 patients who responded or had stable disease after chemotherapy with three cycles of an anthracycline followed by three cycles of a taxane were randomized to maintenance therapy with pegylated liposomal doxorubicin (PLD), 40 mg/m² once every 4 weeks for six cycles, or to observation. The study population did not include patients with grade 2 or higher cardiac dysfunction.

Patients in the experimental arm received a median of six cycles of maintenance PLD, and 50% completed all planned cycles; 20% discontinued because of toxicity.

PLD maintenance was associated with a significant improvement in disease-free survival. The time from randomization to disease progression was 8.38 months for the PLD maintenance arm vs 5.06 months for the observation arm, for a 46% reduced risk of recurrence (P = .0006). Time from initial induction treatment to disease progression was 13.2 months vs 10.2 months, for a 47% reduced risk of recurrence (P = .0005).

In the first 6 months after randomization, 28 patients on PLD maintenance therapy progressed, compared with 48 in the observation arm, while 30 patients in the PLD arm and 18 in the observation arm progressed during the following 18 months. "This finding suggests that the main treatment effect occurs during the administration of this drug," Dr. Alba said.

As expected, toxicity was greater on the PLD arm but was mostly grade 1-2. Neutropenia grade 3-4 was seen in 12% of treatment patients, compared with no patients in the observation arm; however, only 2.6% of PLD patients developed febrile neutropenia. No patients developed grade 3-4 anemia.

Grade 3-4 nonhematologic toxicity was rare with PLD; there was no grade 3-4 alopecia or nausea/vomiting; 3% of PLD patients had grade 3-4 fatigue, 4% had hand-foot syndrome, and 5% had mucositis. There was no grade 3-4 nonhematologic toxicity on the observation arm.

Only two patients (3%) on PLD had a drop in left ventricular ejection fraction of less than 50%; no cases occurred with observation. A decrease of 10% or more was seen in 6% and 1%, respectively.

"Toxicity is infrequent and manageable, and cardiotoxicity has not been relevant," Dr. Alba said.

He concluded that maintenance therapy with PLD is a good therapeutic option in patients with metastatic breast cancer who are stable after first-line treatment, since it significantly prolongs time to progression.

"Based on these results, adding PLD as maintenance will become the standard arm on future GEICAM studies," Dr. Alba said.

Martine Piccart, MD, PhD, of the Institut Jules Bordet, Brussels, Belgium, commented, "I don't think this is a new standard of care unless you see a survival benefit, and I discourage you from adopting it as the next standard."

Dr. Alba responded, "This is not for everyone. For future GEICAM trials, this will be our standard, but it is too early to say whether it should be the global standard."