Impact of Primary Pegfilgrastim Prophylaxis on Relative Dose Intensity in Neoadjuvant/Adjuvant FEC-100 Chemotherapy

Abstract

Background/Aim: This study aimed was to clarify the impact of pegfilgrastim (PEG) 3.6 mg primary prophylaxis of febrile neutropenia (FN) on the average relative dose intensity (ARDI) of neoadjuvant/adjuvant FEC-100 for breast cancer. Materials and Methods: This retrospective, single-centre cohort study including 296 patients who received FEC-100 compared PEG and non-PEG groups. The PEG group received PEG 3.6 mg as a single subcutaneous injection in each study cycle. The primary endpoint was the ARDI of FEC-100. The secondary endpoints were patient percentage of ARDI≥85%, factors associated with ARDI≥85%, and reasons for reduced ARDI. Results: The PEG group showed significantly higher mean ARDI (95.6% versus 90.7%, p<0.001) and patient percentage of ARDI≥85% (93.0% versus 79.9%, p=0.001). PEG was significantly associated with ARDI≥85% (p=0.009). Neutropenia and FN, the main reasons for reduced ARDI, were significantly lower in the PEG group (p<0.05). Conclusion: Primary PEG 3.6 mg prophylaxis increased the ARDI of FEC-100.FEC-100 chemotherapy (fluorouracil, epirubicin, and cyclophosphamide) has been established as a standard neoadjuvant or adjuvant therapy for breast cancer (1-3) and is widely used in clinical practice (4, 5). In the phase II clinical study for FEC-100 chemotherapy in Japan, grade ≥3 neutropenia and febrile neutropenia (FN) occurred in 44% and 20% of patients, respectively, and dose reduction due to their toxicities was required in about 15% (6). Dose reduction and treatment delay due to toxicities affect relative dose intensity (RDI).In a comprehensive systematic review and meta-analysis of 17 randomised, controlled trials (RCTs), neutropenic events had a significant impact on RDI for patients receiving adjuvant anthracycline-based chemotherapy for early breast cancer. According to the results of this study, the decrease rate of RDI due to neutropenia was a mean of 8.9% and a median of 8.2%. Furthermore, of the patients with neutropenic events, 32% did not achieve an RDI of 85%, compared to 7% of patients in the group with no events (7). Bonadonna et al. (8) and Chirivella et al. (9) reported that patients who received an RDI≥85% have a significantly higher probability of survival. The French Adjuvant Study Group 05 Randomized Trial showed benefit in terms of disease-free survival and overall survival when the epirubicin dose was increased from 50 mg/m 2 to 100 mg/m 2 in FEC chemotherapy (10). Given the above results, maintaining RDI as high as possible might contribute greatly to survival.Updated guidelines from the American Society of Clinical Oncologists (ASCO) (11), the National Comprehensive Cancer Network (NCCN) (12), the European Organization for the Research and Treatment of Cancer (EORTC) (13), and the Japanese Society of Medical Oncology (JSMO) (14) recommend routine use of granulocyte colony-stimulating factors (G-CSF) for chemotherapy regimens with an FN risk ≥20%. For regimens with an FN risk of 10-20%, individual patient risk factors such as age and disease stage should be taken i...

Primary Prophylaxis of Febrile Neutropenia With Pegfilgrastim in Small-cell Lung Cancer Patients Receiving Amrubicin as Second-line Therapy

“…Inoue et al demonstrated in a randomized phase II trial comparing AMR with TOPO in patients with SCLC previously treated with platinum-containing chemotherapy that the median number of treatment cycles and median PFS in the AMR arm were 3 (range=1-7 months) and 3.5 months, respectively (5). Moreover, primary prophylaxis of PEG has been reported to increase relative dose intensity (RDI) of neoadjuvant/adjuvant FEC-100 (fluorouracil, epirubicin and cyclophosphamide) for breast cancer and to maintain RDI of carboplatin plus docetaxel or paclitaxel for ovarian cancer (21,22). Therefore, treatment continuation with primary prophylactic G-CSF support may have provided this improved efficacy in this study, but further large-scale studies are needed to elucidate them.…”

Evaluation of the Antiemetic Effect of Premedication Optimized by Pharmaceutical Support in Cisplatin Regimens

“…CINV control is an important factor in conducting antineoplastic chemotherapy. 10) As the regimen revision resulted in a decrease in metoclopramide use in the conventional dose group, the revision of the gastrointestinal surgery regimen was an effective pharmaceutical support measure to maintain the treatment intensity and not reduce the patient's QOL. In the Department of Gastroenterological Surgery, the proportion in the reduced dose group regarding antineoplastic agent was significantly higher in the former regimen group (p = 0.019).…”

“…When a patient with lower PS was treated with high-intensity and highly emetogenic antineoplastic agents, poor CINV control may have been associated with treatment interruption. 10) Therefore, attention must be paid to such incompatibilities. In particular, it has already been reported that CINV is more likely to occur in females than in males.…”

“…Moreover, Mann-Whitney U-test was applied to assess between-group differences in the number of metoclopramide injection administrations per rescue. In the analysis of metoclopramide injection, the dosage of the antineoplastic agent was a factor that affected CINV, 10) and the analysis was conducted after the dosage of the agent was classified into the conventional dose group and the reduced dose group. A statistical significance threshold of <5% was used in all analyses.…”

Clinical Outcomes of Secondary Prophylactic Granulocyte Colony-Stimulating Factors in Breast Cancer Patients at a Risk of Neutropenia with Doxorubicin and Cyclophosphamide-Based Chemotherapy

“…The American Society of Clinical Oncology (ASCO), the European Organization for Research and Treatment of Cancer (EORTC), and the National Comprehensive Cancer Network (NCCN) guidelines recommend using primary prophylactic granulocyte colony-stimulating factor (G-CSF) when the risk of FN is >20% for all planned cycles of treatment [11][12][13]. The prophylactic use of G-CSF contributes to successful remission from breast cancer by maintaining ≥ 85% of the planned relative dose intensity (RDI) of chemo-medications during chemotherapy [14][15][16][17]. Moreover, the ASCO, EORTC, and NCCN guidelines define AC-based chemotherapy as an intermediate-risk (10-20%) regimen regarding FN and recommend considering secondary prophylaxis with G-CSF [11][12][13].…”