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
"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.