Pegfilgrastim is a white blood cell growth factor with labeled use to decrease the incidence of infection (as manifested by febrile neutropenia), in patients with nonmyeloid malignancies receiving myelosuppressive cancer therapy associated with a clinically significant incidence of FN.1 The FDA label recommends administration starting at least 24 hours after the completion of chemotherapy.
To improve compliance and convenience for patients by not having to return 24 hours after chemotherapy for administration there is an interest in same day administration. A survey of physicians who administer pegfilgrastim reported that 31.6% were treated on a “same-day” schedule utilizing patient related considerations in the decision such as patient/caregiver travel distance and practice related consideration such as burden on the practice for next day administration as determining factors.2
Burris et al3 conducted a study to compare data on severe (grade 4) neutropenia duration and FN incidence in patients receiving chemotherapy with pegfilgrastim administered the same day or 24 hours after chemotherapy. These were similar, randomized, double-blind phase II noninferiority studies of patients with lymphoma or non–small-cell lung (NSCLC), breast, or ovarian cancer. Each study was analyzed separately. The primary end point in each study was cycle-1 severe neutropenia duration. Approximately 90 patients per study were randomly assigned at a ratio of 1:1 to receive pegfilgrastim 6 mg once per cycle on the day of chemotherapy or the day after (with placebo on the alternate day). In 4 studies, 272 patients received chemotherapy and 1 or more doses of pegfilgrastim (133 same day, 139 next day). Three studies (breast, lymphoma, NSCLC) enrolled an adequate number of patients for analysis. However, in the NSCLC study, the neutropenic rate was lower than expected (only 2 patients per arm experienced grade 4 neutropenia). In the breast cancer study, the mean cycle-1 severe neutropenia duration was 1.2 days (95% confidence limit [CL], 0.7 to 1.6) longer in the same-day compared with the next-day group (mean, 2.6 v 1.4 days). In the lymphoma study, the mean cycle-1 severe neutropenia duration was 0.9 days (95% CL, 0.3 to 1.4) longer in the same-day compared with the next-day group (mean, 2.1 v 1.2 days). In the breast and lymphoma studies, the ANC profile for same-day patients was earlier, deeper, and longer compared with that for next-day patients, although the results indicate that same-day administration was statistically noninferior to next-day administration according to neutropenia duration. The authors concluded that pegfilgrastim administered at least 24 hours after chemotherapy completion is recommended.
A retrospective study of patients who received chemotherapy and prophylactic same-day or next-day pegfilgrastim found that in cycle 1, 117 patients received same-day pegfilgrastim and 180 patients received next-day pegfilgrastim. FN episodes in cycle 1 occurred in 6.0% versus 6.7% of patients with same-day versus next-day pegfilgrastim, respectively (p = 0.814). Across all cycles, 8.5 and 9.4% of patients experienced >/=1 FN episode after same-day versus next-day pegfilgrastim, respectively (p = 0.793). In the breast cancer patient subgroup, FN occurred 3.2% of same-day pegfilgrastim cycles versus 1.8% of next-day pegfilgrastim cycles (p = 0.938). The authors reached the conclusion that there was no significant difference between same-day and next-day pegfilgrastim administration.4
McBride et. al.5 looked at 93 patients who received 460 cycles of CHOP-like chemotherapy. The incidence of FN and grade 3/4 chemotherapy-induced neutropenia was 5% and 16.5%, respectively. In 401 cycles, pegfilgrastim was administered same-day versus 12 cycles next-day. FN occurred in 17 cycles versus 0 cycles (p = 1.00) and grade 3/4 chemotherapy-induced neutropenia in 65 cycles (16.2%) versus 1 cycle (16.7%; p = 1.00) with same-day versus next-day pegfilgrastim administration, respectively. They concluded that pegfilgrastim may be safely administered on the same day as chemotherapy in patients with lymphoma receiving CHOP-like chemotherapy.
A systematic literature review evaluated the relative merits of same-day versus next-day dosing of pegfilgrastim. A broad Ovid MEDLINE® and Embase® literature search was conducted that examined all publications indexed before May 9, 2016, that compared same-day versus next-day pegfilgrastim administration. The first part of the systematic literature search identified 1736 publications. After elimination of duplicates, title/abstract screening was conducted on 1440 records, and full text review was conducted on 449 publications. Eleven publications met all criteria and are included in this systematic review; of these, 4 included data from randomized or single arm prospective studies, and 7 were retrospective studies. In most studies included in this review and across a variety of tumor types, administration of pegfilgrastim at least 24 h after myelosuppressive chemotherapy resulted in improved patient outcomes. The authors concluded that data from multiple publications supports administration of pegfilgrastim at least 1 day after chemotherapy.6
A small study of 46 patients were treated for the following malignancies: 35 (76%) epithelial ovarian, 6 (13%) primary peritoneal, and 5 (11.0%) ovarian germ cell or stromal cell carcinoma. All patients met the current guidelines of using CSF for prophylaxis against FN. A total of 269 cycles of chemotherapy were administered. All patients received pegfilgrastim within 1 hour of the completion of chemotherapy administration. Grade 1 or 2 neutropenia developed in 10 cycles (3.7%), and the mean ANC was 4926/uL (range, 1,293-24,300). No patients had febrile neutropenic episodes, hospitalizations, or antibiotic use secondary to neutropenia, nor did they have dose reductions or chemotherapy delays due to neutropenia. The authors felt that administration of pegfilgrastim on the same day as myelosuppressive chemotherapy in patients with ovarian or primary peritoneal cancer may be a convenient, safe, and effective approach.7
Whitworth et.al.8 sought to compare the safety and efficacy of day 1 pegfilgrastim administration to day 2 administration in patients with gynecologic malignancies. They retrospectively evaluated patients receiving both chemotherapy and pegfilgrastim from June 1, 2006, to August 31, 2007, for a gynecologic malignancy. After administration of chemotherapy, all patients either received 6 mg of pegfilgrastim subcutaneously on day 1 or day 2. 1226 administrations of pegfilgrastim in 230 patients were identified. 490 administrations of pegfilgrastim were given on day 1 compared to 736 on day 2. 70% of patients had ovarian cancer with a median age of 64 years (range 15-88). 79% of patients had stage III, IV, or recurrent disease and 67% were undergoing primary chemotherapy. The most common chemotherapy was docetaxel/carboplatin (53%) followed by paclitaxel/carboplatin (19%). The mean ANC nadir was 4810/mm(3) in the day 1 cohort compared to 4212/mm(3) in the day 2 cohort (p=.004). The incidence of Grade 3/4 neutropenia was similar in both groups (4.9% in day 1 vs. 5.7% in day 2; p=.63). Grade 3/4 febrile neutropenia was uncommon in both cohorts (0 episodes vs. 3 episodes; p=.41). Treatment delays were similar in both cohorts (5.9% vs. 7.5%; p=.35). Dose modifications were also similar in both cohorts (2.8% vs. 5.3%; p=.06). Their conclusion was that day 1 administration of pegfilgrastim is as effective as day 2 administration in the prevention of neutropenia in patients with gynecologic malignancies.