Temozolomide safe in patients with renal dysfunction, study claims

USA: Patients with severe renal impairment, defined as an eGFR < 36 mL/min/1.73m2, experience hematologic toxicity comparable to that of patients with normal renal function, says an article published in the Journal of Neuro-Oncology.

The major chemotherapy agent used to treat high grade astrocytoma is temozolomide (TMZ), a cytotoxic DNA alkylating agent. Since methylhydrazine, the primary alkylator, is not recovered in urine, renal function is not anticipated to have an impact on clearance. According to the TMZ prescribing instructions, people with impaired renal function (eGFR 36 mL/min/1.73 m2) have not had their pharmacokinetics examined. In order to assess the safety of delivering TMZ at full dosage, Kayla Garzio and team reviewed clinical data with TMZ in patients with compromised renal function.

This study's main goal was to describe the frequency and severity of thrombocytopenia in people who received TMZ for high-grade gliomas (HGG) or primary CNS lymphomas (PCNSL) and had eGFR levels below < 60/min/1.73 m2. The frequency and intensity of neutropenia, lymphopenia hepatotoxicity, and the total number of TMZ cycles were secondary objectives. To find instances for this investigation, medical records of patients with HGG or PCNSL treated with TMZ between October 1, 2016, and September 30, 2019 were obtained.

The key findings of this study were:

1. For this study, 32 patients were eligible. 38/39 cycles (97%) of the seven patients with eGFR < 36 mL/min/1.73m2 were finished without grade 3–4 thrombocytopenia.

2. Grade 3-4 lymphopenia occurred in 5 cycles (15%) while grade 3-4 neutropenia occurred in no individuals.

3. One patient stopped taking TMZ seven days before the end of the radiation treatment because of thrombocytopenia.

In conclusion, due to a paucity of information and cautions against usage in the package insert, it may have been previously advised, restricted, or avoided to administer TMZ to this patient population. Our institution's experience suggests that individuals with eGFR < 36 mL/min/1.73m2 can receive TMZ with a side effect profile that is comparable to that of people without renal impairment. However, it is suggested that blood counts and chemistries be monitored cautiously.

Reference: 

Garzio, K., McElroy, K., Grossman, S., Holdhoff, M., Ozer, B., & Yankulina, O. (2022). Safety of temozolomide use in adult patients with renal dysfunction. In Journal of Neuro-Oncology. Springer Science and Business Media LLC. https://doi.org/10.1007/s11060-022-04098-1