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Am J Clin Oncol. 2008 Aug;31(4):369-74. doi: 10.1097/COC.0b013e318165c01d.

Identifying patients at high risk for neutropenic complications during chemotherapy for metastatic breast cancer with doxorubicin or pegylated liposomal doxorubicin: the development of a prediction model.

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Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.



To develop a cycle-based risk prediction model for neutropenic complications (NC) during chemotherapy with doxorubicin (DOX) or a pegylated liposomal formulation (PLD) for patients with metastatic breast cancer (MBC).


Data analyzed was from a phase III, randomized clinical trial of DOX (60 mg/m(2) every 3 weeks) or PLD (50 mg/m(2) every 4 weeks) for the first line therapy for MBC (n = 509) (O'Brien et al, Ann Oncol. 2004;15:440-449). NC were defined as an absolute neutrophil count < or =1.5 x 10(9) cells/L (ie, > or =grade II) before the next cycle, febrile neutropenia or neutropenia with a documented infection. Patient and hematologic factors potentially associated with NC were evaluated. Factors with a P value of < or =0.25 within a cycle were included in a generalized estimating equations regression model. Using backward elimination, we derived a risk scoring algorithm (range 0-63) from the final reduced model.


Risk factors retained in the model included poor performance status, absolute neutrophil count < or =2.0 x 10(9) cells/L in the previous cycle, the first cycle of chemotherapy, DOX versus PLD and advanced age. A precycle risk score from > or =25 to <40 for a given patient was identified as being the optimal threshold for sensitivity (58.0%) and specificity (78.7%). Patients with a score at or beyond this threshold would be considered at high risk for developing NC in later cycles.


The use of this model may enhance patient care by targeting preventative therapies (eg, granulocyte colony stimulating factor or PLD) to those MBC patients most likely to experience NC during anthracycline-based chemotherapy.

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