Retrospective Study Evaluating the Safety of Administering Pegfilgrastim on the Final Day of 5-Fluorouracil Continuous IV Infusion
Amber Draper, PharmD, BCOP
Oncology Clinical Pharmacy Specialist, GI Oncology
Clinical Coordinator, Oncology Pharmacy
Emory Healthcare, Winship Cancer Institute
5-Fluorouracil continuous intravenous infusion (5-FUCI) is administered as a 46-48 hour continuous IV infusion (CIVI), on an every two week schedule. It is administered along with oxaliplatin and/ or irinotecan in chemotherapeutic regimens used to treat gastro-intestinal (GI) malignancies, including colorectal, pancreatic and cholangiocarcinoma cancers. When 5-FU is administered concomitantly with oxaliplatin or irinotecan, neutropenia is more likely to occur and can lead to negative outcomes, such as treatment delays and hospitalization for febrile neutropenia (FN).1,2 In these scenarios, pegfilgrastim (Neulasta®) can be administered to maintain dose intensity and density in patients with GI malignancies experiencing neutropenia. However, the package insert (PI) recommends that pegfilgrastim not be administered 14 days before, or within 24 hours following, administration of cytotoxic chemotherapy.3 For this reason, some payors are unwilling to pay for administration of pegfilgrastim on the same day as 5-FUCI pump disconnect.
Following the currently approved indications, GI cancer patients would require an additional clinic visit for pegfilgrastim to be administered on day 4, the day after 5-FUCI pump disconnect. This is both cumbersome and costly for our patients. The pegfilgrastim on-body injector could circumvent this problem; however, we have seen many payors preferring biosimilar products that do not have a similar delivery system. The study reviewed here, “Retrospective study evaluating the safety of administering pegfilgrastim on the final day of 5-Fluorouracil continuous IV infusion,” attempts to determine the incidence of grade 3-4 neutropenia and FN when pegfilgrastim was administered on the final day of 5-FUCI.4
In this study, charts of 300 patients who received pegfilgrastim on the final day of 5-FUCI at two cancer centers were reviewed for demographics (age, race, gender), cancer diagnosis, stage of disease, chemotherapy regimen, number of prior therapies, and prior radiation therapy. FN risk factors were accessed for each patient based on the National Comprehensive Cancer Network (NCCN) Myeloid Growth Factors 2017 guidelines. For each chemotherapy cycle (14 days), the following data were collected: chemotherapy administration date, pegfilgrastim administration date, number of days between pegfilgrastim administration, and date of next chemotherapy cycle. The number of treatment delays and dose reductions for any reason were also collected per chemotherapy cycle. To assess for myelosuppression, the absolute neutrophil count on day 1 of each chemotherapy cycle was documented.
A total of 1845 chemotherapy cycles were evaluated. Out of 300 patients, three patients experienced grade 3 neutropenia (1%) and 2 experienced grade 4 neutropenia (0.7%) when pegfilgrastim was administered on the final day of 5-FUCI. The risk of FN and hospitalization occurring in a patient receiving pegfilgrastim on the final day of 5-FUCI was 0.7% (CI 0.001-0.024). Patients receiving pegfilgrastim on the final day of 5-FUCI had an absolute risk of experiencing a treatment delay or dose reduction due to grade 3 or 4 neutropenia of 1.3% and 1%, respectively.
Clinical guidelines and the PI recommend administration of pegfilgrastim 24-72 hours after the administration of chemotherapy. However, due to logistical challenges and related costs, same day administration on the final day of 5-FUCI infusion is often preferred by providers and patients.5,6 The results of this study demonstrated that rates of grade 3 and 4 neutropenia were low when pegfilgrastim was administered on the final day of 5-FUCI. Additionally, dose delays and reductions due to neutropenia were low when pegfilgrastim was administered on the same day as chemotherapy. These data suggest that administering pegfilgrastim on the final day of 46-48 hour 5-FUCI does not increase myelosuppression or FN episodes.
Several prospective and retrospective clinical trials have examined the efficacy and safety of administering pegfilgrastim on the same day as cytotoxic chemotherapy with contradictory results. However, GI malignancies treated with 5-FUCI were underrepresented in a majority of these trials. The results of this retrospective review of patients receiving 5-FUCI suggest that administering pegfilgrastim on the final day of 5-FUCI does not lead to an increase in myelosuppression or FN. Based on these results, same day administration may be feasible for this patient population; however, further studies are needed to confirm these findings.
- Andre T, Boni C, and Mounedji-Boudiaf L. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004; 350: 2343-51.
- Douillard JY, Cunningham D, and Roth AD. Irinotecan combined with fluorouracil compared with fluorouracil alone as first line treatment for metastatic colorectal cancer: a multicenter randomized trial. Lancet. 2000; 355: 1041-47.
- Neulasta (pegfilgrastim) [package insert]. California: Amgen Inc; 2017.
- Draper AS, Lafollette J, and Wu CS. Retrospective study evaluating the safety of administering pegfilgrastim on the final day of 5-fluorouracil continuous intravenous infusion. J Oncol Pharm Pract. 2020. doi:10.1177/1078155220945771 [published online ahead of print, 2020 Aug 6]
- Marion S, Tzivelekis S, and Darden C. Same day administration of pegfilgrastim following myelosuppresivve chemotherapy: clinical practice and provider rationale. Support Care Cancer. 2016; 24: 3889-3896.
- Hauber AB, Mange B, and Price MA. Administration options for pegfilgrastim prophylaxis: patient and physician preferences from a cross-sectional survey. Support Care Cancer. 2018; 26: 251-260.