Evaluating Omission of Granulocyte Colony-stimulating Factors in Breast Cancer Patients Receiving Paclitaxel Portion of Dose-dense Adriamycin-cyclophosphamide and Paclitaxel Chemotherapy

Optimal curative chemotherapy treatment in the early-stage setting for breast cancer patients can reduce the risk of recurrence and result in improvement in breast cancer survival. The pivotal Cancer and Leukemia Group B (CALGB) 9741 clinical trial demonstrated improved efficacy from administering 4 cycles of adriamycin and cyclophosphamide (AC) followed by 4 cycles of paclitaxel using a dose-dense schedule every 2-weeks instead of every 3 weeks in patients with high-risk early-stage breast cancer. It has since become a widely accepted standard care treatment option. Granulocyte colony-stimulating factor (G-CSF) such as filgrastim (FIL) and pegfilgrastim (PEG) are key supportive medications used with the dose-dense regimen to facilitate timely recovery of neutrophil count before the next cycle of treatment. However, G-CSF is associated with increased bone pain after chemotherapy (up to 40%) and drug-induced fever, which can result in additional clinical or emergency room visits. Clinicians have questioned if primary prophylactic G-CSF use is necessary with paclitaxel in the dose-dense regimen and the risk of hematological toxicity, such as the risk of low neutrophils and the risk of infection is lower with paclitaxel. Results from two retrospective studies suggest that it is safe and feasible to omit G-CSF during the paclitaxel portion of the DD-AC/T regimen. Based on the current trial data, there is a stong suggestion that it is safe, feasible and likely preferable to omit G-CSF during the paclitaxel portion of DD-AC/T chemotherapy. Given the majority of chemotherapy dose delays are related to issues such as bone pain (from G-CSF and paclitaxel) and peripheral neuropathy (from paclitaxel), and this may even be exacerbated by the use of G-CSF, it is anticipated that omitting G-CSF during paclitaxel chemotherapy may improve completion rates while improving health related quality of life (HR-QoL). Therefore, the researchers propose a randomized study to further evaluate patient-reported bone pain and HR-QoL from the omission of primary prophylactic G-CSF use during the paclitaxel portion of DD-AC/T chemotherapy while demonstrating supportive evidence that omitting G-CSF is safe and feasible.

• Patient-reported bone pain across all paclitaxel cycles [Time frame: After each of the paclitaxel chemotherapy cycles (each cycle is 14 days)]
• Peak bone pain experienced [Time frame: Days 1 to 5 of the each of the paclitaxel chemotherapy cycles (each cycle is 14 days)]
• Patient health-related quality of life [Time frame: Through study completion, average of 12 weeks]
• Rates of completion of 4 cycles of paclitaxel [Time frame: Through study completion, average of 12 weeks]
• Dose-intensity of paclitaxel chemotherapy [Time frame: Through study completion, average of 12 weeks]
• Incidence of febrile neutropenia/neutropenia [Time frame: Through study completion, average of 12 weeks]
• Incidence of treatment-related hospitalizations/ER visits [Time frame: Through study completion, average of 12 weeks]
• Healthcare resource utilization: Emergency Room Visits [Time frame: Through study completion, average of 12 weeks]
• Healthcare resource utilization: Planned and Unplanned Provider Visits [Time frame: Through study completion, average of 12 weeks]
• Healthcare resource utilization: Phone Calls and Emails [Time frame: Through study completion, average of 12 weeks]
• Cost-effectiveness ratios [Time frame: Through study completion, average of 12 weeks]
• Incidence of chemotherapy-related mortality [Time frame: Through study completion, average of 12 weeks]