Abstract
Background:Vincristine (VCR) is a commonly utilized chemotherapy agent for the treatment of pediatric cancers including leukemia, lymphoma, and various solid tumors. Vincristine interferes with microtubule formation impeding the proper division of cancer cells. Although VCR is an effective and potent chemotherapy drug its use requires careful monitoring due to potentially harmful side effects. The FDA label for VCR states that fever is a possible side effect. In pediatric oncology patients, a febrile event is considered a medical emergency and prompts a sepsis workup often involving hospitalization and an infectious disease workup. Reports on vincristine-induced fever in literature remain minimal with true incidence still unknown. This study sought to determine the incidence of non-infectious fever following vincristine administration and to compare this rate to that of other chemotherapeutic agents.
Methods: To determine the prevalence of vincristine-induced fevers in a significant patient population we collaborated with the Clinical Research Institute at Texas Tech University Health Sciences Center on an IRB approved retrospective chart review. Pediatric patients included children and adolescents (0-17 years old) in Lubbock, TX who received chemotherapy for a cancer diagnosis between January 2017 and August 2024. Fever was defined as a single recorded temperature at or exceeding 100.4 degrees Fahrenheit. Fever occurring within 48 hours of chemotherapy administration, with a negative infectious workup, was considered chemotherapy related. For each defined fever, the preceding 48-hour chemotherapy regimen was categorized as (1) vincristine-related, (2) other chemotherapy-related, or (3) vincristine and other chemotherapy-related. The proportion of fever events attributable to each category was compared using Fisher's exact test. Following data collection fever scores were calculated using methods outlined by Ammann, RA. et al. (2010) to predict the risk of adverse events in pediatric oncology patients who experience fever and neutropenia. A two-sided p-value less than 0.05 was considered statistically significant. Statistical analysis was performed using R 4.3.2.
Results: The analysis included 168 pediatric patients from two local treatment centers who fit inclusion criteria. The study comprised of 70 female and 98 male patients with a mean age of 6.9 years at initial cancer diagnosis. Leukemia was the most common diagnosis, occurring in 54% of patients, followed by the other solid tumors (19%), sarcoma (9.5%), neuroblastoma/kidney (8.9%), and brain/spine tumors (8.9%). A total of 132 patients (79%) received vincristine during treatment. Over the study period, 21 non-infectious fever events were identified. The distribution of these fever events was analyzed based on the preceding chemotherapy exposure. Of the 21 events, 3 (14%) occurred within 48 hours of vincristine monotherapy, 12 (57%) followed multidrug chemotherapy with vincristine and 6 (29%) occurred following chemotherapy administration excluding vincristine. No statistically significant difference was found in the proportion of fevers attributed to vincristine-containing versus non-vincristine containing treatments (p-value greater than 0.9 using Fisher's exact test). Fever scores between patients who did and did not receive vincristine were statistically insignificant (p=0.90).
Conclusions: In this retrospective analysis of pediatric oncology patients, vincristine administration was not associated with an increased rate of non-infectious febrile events compared to other chemotherapy agents. Our data supports the current standard of care, which includes a thorough and urgent workup for an infectious etiology for any fever event. Expansion of the patient population across multiple treatment centers is warranted to further define the incidence of vincristine-induced fever and better inform the management of fever in this pediatric patient population.
