Temozolomide Is a Potential Therapeutic Tool for Patients With Metastatic Pheochromocytoma/Paraganglioma—Case Report and Review of the Literature

Abstract

Context: Metastatic pheochromocytoma/paraganglioma (MPP) therapy mainly involves radionuclide therapy, chemotherapy, and targeted therapy. In recent years, temozolomide (TMZ) showed great promise in some MMP patients, especially those with SDHB germline mutation. We reported a patient with MPP who did not have any known germline genetic change and responded remarkably well to TMZ monotherapy.Case presentation: The patient was a 41-year-old woman with local and distant recurrence (soft tissues and bone metastases) of retroperitoneal paraganglioma. She suffered from dizziness, palpitation, sweating, weight loss and constipation, with the blood pressure fluctuating substantially from 130/100 mmHg to 190/120 mmHg, although she was on phenoxybenzamine and metoprolol medication. The patient showed clinical and radiological response after 3-cycle TMZ therapy. Upon 15 cycles of TMZ therapy, her symptoms were dramatically alleviated, urinary norepinephrine excretion decreased from 1,840 µg/24 h to 206 µg/24 h, and CT showed that the lesions further shrank. Molecular profiling of the tumor tissue of the patient revealed hypermethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter and a negative immunostaining for MGMT. Globally, only 26 cases of MPP treated with TMZ have been described so far. TMZ is effective, especially in patients with SDHB mutation, which can be explained by the silencing of MGMT expression as a consequence of MGMT promoter hypermethylation in SDHB-mutated tumors. Although, in general, patients with SDHB mutation or MGMT promoter hypermethylation have better response to TMZ, there are also exceptions. Severe side effects are uncommon, with only 17.4% patients experiencing Grade 3 toxicities, including lymphopenia, and hypertension. Tong et al. Temozolomide Is Effective for MPPConclusions: TMZ is effective and safe in MPP patients, and, it may work better on patients with SDHB-related MPP. Measurement of MGMT expression might help assess the tumor sensitivity to TMZ but this needs further systematic investigation.

The use of temozolomide in paediatric metastatic phaeochromocytoma/paraganglioma: A case report and literature review

“…Two small studies ( 19 , 20 ) and several case reports ( 23 ) have found temozolomide to be an effective chemotherapy in a number of patients with metastatic PPGL. Reported response to temozolomide was shown to be greater if the patient had a germline SDHB mutation ( 19 , 20 ).…”

Metastatic pheochromocytoma and paraganglioma: signs and symptoms related to catecholamine secretion

“…Several other studies reported on signs and symptoms in patients with mPPGLs, but comparative data including an appropriate group of patients without metastatic disease was also lacking [ 6 , 14 , 25 ]. Some studies, focusing on specific symptoms, found a higher proportion of patients with mPPGLs complaining of severe constipation compared to those without metastatic disease [ 26 – 28 ]. We could not confirm any difference in constipation between groups, though this complaint is likely associated with larger tumor burden and secretion of norepinephrine than in most of our patients.…”

Metastatic Pheochromocytomas and Abdominal Paragangliomas

“…It is used in neuroendocrine tumors, both as monotherapy and in combination with capecitabine ( 86-89 ). Several case reports have demonstrated that temozolomide also may be active in metastatic PPGLs ( 90 , 91 ). In a consecutive retrospective study, 15 patients with PPGLs, among whom 10 (67%) had SDHB mutation, were treated with temozolomide (median dose 172 mg/m 2 ) daily for 5 days every 28 days ( 70 ).…”