Flores, I.Q., & Ershler, W. (2009). Managing neutropenia in older patients with cancer receiving chemotherapy in a community setting. Clinical Journal of Oncology Nursing, 14, 81–86.

The purpose of the study was to compare the use of pegfilgratim in all chemotherapy cycles with pegfilgrastim use at the clinician’s discretion for the reduction of febrile neutropenia, grade 3 or 4 neutropenia, dose delay, dose reduction, hospitalization, antibiotic use, and infections in older adults with cancer.

Study period was June 2002 to Nov 2004.

Older adults with cancer of the breast, ovary, lung, or aggressive non-Hodgkin lymphoma (NHL) were randomized to pegfilgrastim (subcutaneous injection 6 mg one time per cycle 24 hours after chemotherapy completion staring with cycle one) or secondary prophylaxis with pegfilgrastim (subcutaneous injection 6 mg one time per cycle 24 hours after chemotherapy completion staring after cycle one at physician’s discretion [discretion may be in response to severe neutropenia, netropenia-related events during chemotherapy, dose delays, dose reductions, or no changes in dose or timing]).

• The total sample size was 852.
• All participants were aged 65 years and older.
• The amount of women was 548; the amount of men was 304.
• Key disease characteristics were lung, breast, or ovarian cancer or aggressive NHL.
• In the solid tumor and NHL groups, each of the following age groups were comprised of 33% of the patients: 65–69 years old, 70–74 years old, and 75 years and older.
• 90% were Caucasian and 90% had an ECOG score of 0 or 1.
• The majority of all patients were diagnosed with disease stage III or IV.

• Multi-site  
• Outpatient setting  
• Community cancer centers nationwide

• The phase of care was active treatment
• Application was for elderly care

Phase IV, open-label, randomized, multicenter, community-based trial

• Febrile neutropenia 
• Grade 3 neutropenia
• Chemotherapy regimen
• Solid tumor type
• Pegfilgrastin administered
• Dose delay, dose reduction, hospitalization, and antibiotic use

701 patients with solid tumors. Fifteen were excluded, making the sample size 686 (343 in the pegfilgrastim arm, 343 in the physician discretion arm). Those who completed the study in each arm was 198 in the pegfilgrastim arm  and 175 in the physician discretion arm. Forty-two percent of patients in the discretion arm received pegfilgrastim, most often for grade 3 or 4 neutropenia. There were 151 patients with NHL. Five were excluded, making the sample size 146 (73 in the pegfilgrastim arm, 73 in the physician discretion arm). Thirty-eight patients in each arm completed the study. In the discretion arm, 64% received pegfilgratim.
 

Febrile neutropenia was lower in the all-cycle pegfilgrastim arm compared to the discretion arm, with a 60% reduction in incidence of febrile neutropenia for patients with solid tumors (p = 0.001) and 59% reduction of febrile neutropenia for patients with NHL (p = 0.004). Grade 4 febrile neutropenia was 22% for patients with solid tumors and 75% for patients with NHL in the all-cycle pegfilgrastim arm compared to 58% for patients with solid tumors and 86% for patients with NHL in the discretion arm. Rates of febrile neutropenia in the first cycle for patients with solid tumors were 3%, and 7% for NHL patients in the all-cycle pegfilgrastim arm compared to 7% for solid tumors and 25% for NHL patients in the discretion arm.

Overall, for patients with solid tumors, the all-cycle pegfilgrastim arm had lower rates of grade 3 or 4 neutropenia, dose delays, dose reductions, decreased hospitalizations, and decreased antibiotic use compared to the discretion arm; and similarly for patients with NHL with the exceptions of higher rates of dose delay and dose reductions in the all-cycle pegfilgrastim arm. None of these findings were statistically significant.
 

The most serious adverse event related to pegfilgrastim use was bone pain (12%) in the solid tumor group and in the NHL group (9%) for those receiving all-cycle pegfilgrastim compared to 5% and 4%, respectively, for the discretion arm.

Pegfilgrastin use in older adults undergoing chemotherapy for cancer of the lung, breast, or ovary, or for NHL is safe and effective with use starting in the first cycle for the reduction of febrile neutropenia, grade 3 or 4 neutropenia, febrile neutropenia-related hospitalizations, and antibiotic use. Dose delay and dose reduction were shown to be increased for patients with NHL who received pegfilgrastin at all cycles compared to physician discretion, which may be due to increased use of pegfilgrastin through physician discretion in this population. In addition, due to the use of pegfilgrastin by physician discretion as the comparison group and the unknown information about frequency of dosing in the discretion arm outside of the majority beginning pegfilgrastin treatment following a grade 3 or 4 febrile neutropenic event, coupled with limited statistically significant outcomes, it is difficult to have a definitive conclusion based on these findings. Clinically, however, the outcomes do appear favorable towards use of pegfilgrastin beginning with the first cycle.

• This study was funded by Amgen, the manufacturer of pegfilgrastim, and the study was not blinded. 
• The use of pegfilgrastim for neutropenia and related adverse events in patients with other types of malignancies were not evaluated in this study.
• Fewer patients with NHL were able to be randomized to the discretion arm since physicians often wanted pegfilgrastim started early in these patients due to known neutropenic outcomes.
• In addition, this article was a replication of the article by Balducci et al. (2007), which was the original report of the findings; therefore, this article published two years after the original does not add to the knowledge of efficacy of use of pegfilgrastim.

The administration of pegfilgrastin starting with the first cycle of chemotherapy may reduce neutropenic events and related complications in older adults with cancer. Nurses can be at the forefront of advocating for this therapy, administering it, and monitoring patients for effective outcomes and/or adverse events.