The development of a predictive model to estimate cardiotoxic risk for patients with metastatic breast cancer receiving anthracyclines.

BACKGROUND: Cardiac toxicity from anthracyclines (ACH) can lead to therapy discontinuation, hospitalization or congestive heart failure (CHF). Since such risk may vary by patient, we developed and tested a risk-prediction tool for cardiac toxicity in metastatic breast cancer (MBC) patients receiving chemotherapy with doxorubicin, either in its traditional (DOX) or pegylated liposomal (PLD) formulation.
METHODS: Data was obtained (n = 509) from a randomized clinical trial of MBC patients assigned either DOX (60 mg/m(2) every 3 weeks) or PLD (50 mg/m(2) every 4 weeks) (O'Brien Ann Oncol 15, 440-449, 2004). Patient, disease and treatment factors were identified for each cycle of therapy. Factors with a P-value of <or=0.25 with >or=grade 2 cardiac toxicity following a cycle were retained and included in a generalized estimating equations (GEE) regression model A risk scoring algorithm (range 0-62) was then developed from the final model.
RESULTS: Factors predictive of cardiac toxicity included an interaction effect between DOX and the number of cumulative cycles, patient age and weight, previous ACH exposure and poor performance status. A ROC analysis had an area under the curve (AUC) of 0.84 (95% CI: 0.79-0.89). A precycle risk score cutoff of >or=30 to <40 was identified to optimally balance sensitivity (58.5%) and specificity (89.0%). Patients with a score in a given cycle, within or above this threshold, would be considered at high risk for cardiac toxicity.
CONCLUSION: Our model provides patient specific risk information that could be helpful in assessing the risks and benefits of anthracyclines in the MBC patients.

RCT Entities:   Population Interventions Outcomes