Research presented at the 37th annual meeting of
the American Society of Clinical Oncology
(ASCO)
in San Francisco showed that after long-term evaluation (at 5 years), the
cardiotoxic potential of the AT regimen (doxorubicin [Adriamycin], paclitaxel
[Taxol]) for breast cancer patients is low.
"Our findings confirm that congestive heart failure only
occurs during treatment and mainly in patients who are given doxorubicin for six
or more cycles. By contrast, the level of cardiotoxicity is very low in patients
who receive between four and six cycles of doxorubicin (up to a maximum dose of
360 mg/m2)," said presenter Pinuccia Valagussa of the Istituto Nazionale
Tumore, Milan, Italy, and lead author of the study. "This is an important
finding since we know that the majority of patients respond to the
doxorubicin/paclitaxel regimen within the first four cycles of treatment."
A total of 141 patients were enrolled in three trials conducted
at the Istituto Nazionale Tumori from 1993 to 1998. Patients were evaluated
every 3 months during therapy and subsequently every 12 months for up to
5 years (median: 52 months). All patients entering the trials were screened
for evidence of active heart disease, and only patients with left-ventricular
ejection fractions within the normal range, good blood pressure control, and no
history of significant heart disease were entered into these studies.
Cardiac Events Resolved After Treatment
The three studies found that although asymptomatic signs of
decreased cardiac function (as measured by left-ventricular ejection fraction)
increased progressively during treatment, these events resolved within an
average of 18 months after the completion of treatment. Congestive heart
failure occurred only during treatment and in a disproportionately high number
of patients (5 of 7) who received the highest cumulative dose of doxorubicin
(420 to 480 mg/m2).
"Doxorubicin and paclitaxel are highly active agents in the
treatment of advanced breast cancer. While early studies demonstrated a high
incidence of congestive heart failure due to a high dose of doxorubicin, more
recent trials limiting the dose of doxorubicin to 360 mg/m2
have not observed any increase in cardiotoxicity," said Dr. Valagussa.
In clinical practice, this means that up to six courses
of therapy with doxorubicin (60 mg/m2) and paclitaxel (175 mg/m2) by
3-hour infusion can be administered followed by paclitaxel monotherapy without
any significant
cardiac risk.
Doxorubicin and paclitaxel in combination are the most cytotoxic
agents in the treatment of metastatic breast cancer. Given their clinical
efficacy, relative non-cross-resistance, and differing mechanisms of action,
there is a clear rationale for combining these two agents in both advanced and
early-stage disease. In clinical trials, it has been found that up to 94% of
patients respond to this treatment regimen, and up to 30% of patients achieve a
complete response.
Other Study Confirms Findings
A study published in the Journal of Clinical Oncology by Jassem
et al (19:1707-1715, 2001) supported the findings observed at the Istituto
Nazionale Tumori. The AT regimen was found to be safe and well-tolerated and
resulted in no increase in the incidence of congestive heart failure. The study
also showed that paclitaxel in combination with doxorubicin significantly
improved survival and prolonged median time to disease progression in women with
metastatic breast cancer. The study compared the AT regimen with FAC
(fluorouracil, doxorubicin, cyclophosphamide [Cytoxan, Neosar]). Survival was
superior among patients receiving AT: 23.3 vs 18.3 months. Median time to
disease progression was also significantly superior in the AT arm: 8.3 vs
6.2 months.