Case study 132.1
RJ is a 55-year-old postmenopausal woman who was diagnosed with breast cancer 5 years ago. Mammography revealed a 2 × 1.5 cm mass in the right breast with microcalcifications. Core biopsies of the right breast confirmed an invasive ductal carcinoma, nuclear grade 3, estrogen and progesterone receptor negative (ER−/PR−) and HER-2neu negative. Her past medical history includes no comorbid illnesses. RJ underwent a mastectomy with sentinel lymph node biopsy. She was diagnosed with stage IIB (T2N0M0) hormone-receptor-negative, HER2-negative breast cancer, or “triple-negative” disease. After mastectomy, she received four cycles of dose-dense adjuvant doxorubicin and cyclophosphamide with granulocyte colony-stimulating factor (G-CSF) support followed by four cycles of paclitaxel. She was out of work for 4 months during treatment but did not experience any episodes of febrile neutropenia or dose delays. Two months ago, she began experiencing pain in her hip. A bone scan was performed that indicated a suspicious area of uptake in her lumbar spine, which was confirmed by X-rays. Computed tomography (CT) scan revealed multiple liver lesions, and a biopsy confirmed recurrent breast cancer (ER−/PR). She was initiated on paclitaxel every 3 weeks and has since progressed through treatment. An oncologist is now recommending a new chemotherapy regimen with a breast cancer chemotherapy regimen that has an estimated rate of febrile neutropenia of less than 20%.
• Is filgrastim (G-CSF) or peg-filgrastim (peg-G-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF) (the three colony-stimulating factors (CSFs) that are approved by the US Food and Drug Administration (FDA)) required following the first cycle of this chemotherapy?
For women receiving dos-dense adjuvant breast cancer chemotherapy, guidelines from the American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Center, and European Organization for the Research and Treatment of Cancer recommend G-CSF support for primary prophylaxis for this patient. ASCO guidelines from 1996, 1997, and 2000 recommended that CSFs should be given in a prophylactic setting if the risk for febrile neutropenia is greater than 40%. In 2006, updated guidelines from ASCO lowered the pivot point for CSF use in conjunction with chemotherapy regimens that have rates of chemotherapy-induced febrile neutropenia of 20% or greater. This was based on a randomized clinical trial that randomized patients with breast cancer to receive pegfilgrastim or no G-CSF after docetaxel 100 mg/2 every 3 weeks for four cycles. The incidence of febrile neutropenia (1% vs. 17%) and hospitalization for febrile neutropenia (1% vs. 14%) was reduced by >90% with pegfilgrastim (P < 0.001).
• The patient does develop febrile neutropenia following the first cycle of chemotherapy. She is admitted to the hospital, and broad-spectrum antibiotics are initiated. Should she receive G-CSF, peg-G-CSF, or GM-CSF in addition to the antibiotics?
A data synthesis of 13 trials that compared CSFs plus antibiotics versus antibiotics alone for treatment of established febrile neutropenia indicates that CSFs reduced hospital stays and neutropenia, and had a marginally significant improvement in reducing infection-related mortality (OR: 0.51; 95% CI: 0.26–1.00). However, the potentially beneficial effect was reduced when one low-quality trial that included patients with acute myeloid leukemia was excluded in the sensitivity analysis; also, the study found that administration of CSFs did not improve overall mortality. In practice, a CSF is rarely administered with antibiotics among cancer patients with chemotherapy-induced febrile neutropenia and is generally not recommended.
• The patient is successfully treated for febrile neutropenia and is discharged from the hospital after three days. Her white blood cell count is now 3000 cells/mm3, and she is due for cycle 2, day 1 of the same regimen. Should she receive the same dosages that were administered in cycle 1 with support by a CSF (termed secondary prophylaxis)?
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