Cardiotoxicity with Combination Doxorubicin/Paclitaxel (AT) Is Reversible, Rare With 6 Cycles

MILAN, Italy--The cardiotoxicity seen in preliminary studies of bolus doxorubicin (Adriamycin) plus 3-hour paclitaxel (Taxol) (AT) proved to be reversible and mostly confined to patients who received more than 6 cycles of therapy, according to follow-up data presented at the ASCO meeting.

"These follow-up data indicate that effects on myocardial contractility are reversible after the end of AT and confirm that limiting the total dose of doxorubicin to 360 mg/m² (6 cycles of AT) significantly decreases the risk of congestive heart failure," Pinuccia Valagussa, of the Istituto Nazionale Tumori, Milan, reported at a poster session.

Of the 49 women with metastatic breast carcinoma enrolled in the study, 48 were continuously followed for a median of 42 months (range, 7 to 54 months). The AT regimen was planned for 8 cycles in the first 25 women (to a maximum doxorubicin dose of 480 mg/m²) and for 6 cycles in the last 24 patients (to a maximum doxorubicin dose of 360 mg/m²). Thirty-six women received additional paclitaxel alone (175 to 200 mg/m²) for a median of 5 cycles.

High Response Rate

Response rate was 94%, including 18 complete responses (38%) and 26 partial responses (55%) in the 47 evaluable patients.

Echographic monitoring of heart contractility showed a decrease of left ventricular ejection fraction (LVEF) from baseline of 59% to 51% after completion of therapy (P < .001). The decrease was statistically significant in patients receiving 8 cycles of AT but not in those receiving 6 cycles.

Improvement of LVEF was observed after the end of therapy, and LVEF after a median of 24 months (58%) was similar to that before AT (59%) in 25 evaluable patients.

Seven women (14%) developed congestive heart failure (CHF) within 12 months from the start of AT (median, 8 months). Six were in the group receiving 8 cycles (24.6%) and only one in the group receiving 6 cycles of AT (4.6%).

"LVEF measured before CHF never decreased more than 11% and did not predict for subsequent CHF," Ms. Valagussa said. "All patients who developed CHF responded to diuretics and digoxin, and none died of CHF."

Ms. Valagussa said that after a median follow-up of 42 months, the data indicate good long-term therapeutic activity of AT in patients previously untreated with chemotherapy, with 38% of patients still alive, 9 progression-free, and 5 in continuous unmaintained remission.

"The antitumor activity and cardiac safety profile for doses of AT up to 360 mg/m² of doxorubicin justify the conduct of ongoing adjuvant/neoadjuvant studies of the combination," she concluded.