Research presented at the 37th annual meeting ofthe American Society of Clinical Oncology
Research presented at the 37th annual meeting ofthe American Society of Clinical Oncology(ASCO) in San Francisco showed that after long-term evaluation (at 5 years), thecardiotoxic potential of the AT regimen (doxorubicin [Adriamycin], paclitaxel[Taxol]) for breast cancer patients is low.
"Our findings confirm that congestive heart failure onlyoccurs during treatment and mainly in patients who are given doxorubicin for sixor more cycles. By contrast, the level of cardiotoxicity is very low in patientswho receive between four and six cycles of doxorubicin (up to a maximum dose of360 mg/m2)," said presenter Pinuccia Valagussa of the Istituto NazionaleTumore, Milan, Italy, and lead author of the study. "This is an importantfinding since we know that the majority of patients respond to thedoxorubicin/paclitaxel regimen within the first four cycles of treatment."
A total of 141 patients were enrolled in three trials conductedat the Istituto Nazionale Tumori from 1993 to 1998. Patients were evaluatedevery 3 months during therapy and subsequently every 12 months for up to5 years (median: 52 months). All patients entering the trials were screenedfor evidence of active heart disease, and only patients with left-ventricularejection fractions within the normal range, good blood pressure control, and nohistory of significant heart disease were entered into these studies.
Cardiac Events Resolved After Treatment
The three studies found that although asymptomatic signs ofdecreased cardiac function (as measured by left-ventricular ejection fraction)increased progressively during treatment, these events resolved within anaverage of 18 months after the completion of treatment. Congestive heartfailure occurred only during treatment and in a disproportionately high numberof 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 thetreatment of advanced breast cancer. While early studies demonstrated a highincidence of congestive heart failure due to a high dose of doxorubicin, morerecent 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 coursesof therapy with doxorubicin (60 mg/m2) and paclitaxel (175 mg/m2) by3-hour infusion can be administered followed by paclitaxel monotherapy withoutany significantcardiac risk.
Doxorubicin and paclitaxel in combination are the most cytotoxicagents in the treatment of metastatic breast cancer. Given their clinicalefficacy, relative non-cross-resistance, and differing mechanisms of action,there is a clear rationale for combining these two agents in both advanced andearly-stage disease. In clinical trials, it has been found that up to 94% ofpatients respond to this treatment regimen, and up to 30% of patients achieve acomplete response.
Other Study Confirms Findings
A study published in the Journal of Clinical Oncology by Jassemet al (19:1707-1715, 2001) supported the findings observed at the IstitutoNazionale Tumori. The AT regimen was found to be safe and well-tolerated andresulted in no increase in the incidence of congestive heart failure. The studyalso showed that paclitaxel in combination with doxorubicin significantlyimproved survival and prolonged median time to disease progression in women withmetastatic breast cancer. The study compared the AT regimen with FAC(fluorouracil, doxorubicin, cyclophosphamide [Cytoxan, Neosar]). Survival wassuperior among patients receiving AT: 23.3 vs 18.3 months. Median time todisease progression was also significantly superior in the AT arm: 8.3 vs6.2 months.