Procarbazine, Lomustine and Vincristine Toxicity in Low-Grade Gliomas

Background: Procarbazine, lomustine, and vincristine (PCV) significantly improve survival outcomes in LGG (low-grade gliomas). Administration of PCV to LGG patients increased tremendously over the past years as it went from 2 patients per year between 2005 and 2012 to 23 patients in 2015 only in our centre. However, serious hematological and non-hematological adverse events may occur. The purpose of this study was to evaluate the toxicity of PCV and its clinical relevance in our practice. Methods: We retrospectively reviewed the charts of 57 patients with LGG who received PCV at the Centre hospitalier de l’Université de Montréal between 1 January 2005 and 27 July 2016. Results: Procarbazine, lomustine, and vincristine were associated with severe hematological toxicity as clinically significant grade 3 anemia, neutropenia, and thrombocytopenia occurred in 7%, 10%, and 28% of patients, respectively. Other frequent adverse events such as the increase of liver enzymes, cutaneous rash, neurotoxicity, and vomiting occurred in 65%, 26%, 60%, and 40% of patients, respectively. Patients with prophylactic trimethoprim/sulfamethoxazole had more grade 3 hematological toxicity with PCV, especially anemia (p = 0.040) and thrombocytopenia (p = 0.003) but we found no increase in PCV toxicity in patients on concurrent anticonvulsants. Patients with grade 3 neutropenia had a significantly lower survival (median survival 44.0 months vs. 114.0 months, p = 0.001). Patients who were given PCV at diagnosis had more grade 3 anemia than those who received it at subsequent lines of treatment (p = 0.042). Conclusion: Procarbazine, lomustine, and vincristine increase survival in LGG but were also associated with major hematologic, hepatic, neurologic, and cutaneous toxicity. Anti-Pneumocystis jiroveci pneumonia (PJP) prophylaxis, but not anticonvulsants, enhances hematologic toxicity.