Resolving Myelosuppression with Modafinil in the Treatment of Metastatic Pheochromocytoma and Paraganglioma: A Single Case Study

Temozolomide (TMZ) is an effective treatment option for patients with metastatic Pheochromocytoma and Paraganglioma (mPPGL), but it carries a risk of severe myelosuppression. In this single case study, a 19-year-old male patient receiving TMZ and Sunitinib (SUN) combination therapy developed severe thrombocytopenia and neutropenia after the first dose of the second cycle of TMZ. Following the initiation of Modafinil treatment without traditional supportive treatments, a rapid and significant improvement in platelet and neutrophil levels was observed. The patient remained asymptomatic during this period, and did not require blood product transfusions. In the next cycle, the combination of TMZ and Modafinil was administered, with the addition of Vincristine (VCR). The patient remained asymptomatic throughout the cycle, and platelet counts did not decrease during the combination of Modafinil and TMZ. This suggests that modafinil may increase thrombopoietin (TPO) production by suppressing proinflammatory cytokines such as TNF-α and IL-6. This case is noteworthy as it is the first reported case in the literature of modafinil improving chemotherapy-induced myelosuppression. The findings suggest that modafinil may be a potential agent for reducing hematological toxicities. However, since this observation is based on a single case, more comprehensive preclinical and clinical studies are needed to confirm its effect.