Temozolomide duration and secondary hematological neoplasms: A literature review and implications for patients with neuroendocrine neoplasms

Abstract

Evidence-based recommendations for the optimal duration and sequencing of temozolomide-based treatments in advanced neuroendocrine neoplasms are lacking.Here, we conducted a systematic review of the literature for a descriptive analysis of temozolomide-associated myelodysplasias and leukemias to guide treatment planning. A database search of PubMed and Embase was conducted to identify case reports and/or case series reporting secondary myelodysplasias or leukemias in the setting of temozolomide therapy. Key data items extracted from the studies were the temozolomide dose and duration, latency to hematological disorder, type of secondary malignancy and cytogenetics. Reported cases were summarized graphically. A total of 16 studies with 27 patient cases of therapy-related hematologic neoplasms were identified, all of which were case reports or case series. The median treatment duration and cumulative dose were 19 months and 18,000 mg/m 2 , respectively.Most patients (21/27) were diagnosed on, or after, 12 months, while only one patient was diagnosed before 6 months of treatment. Most of the patients were diagnosed, while still on treatment with temozolomide. Graphically, cases clustered around a cumulative dose of 10,000 to 30,000 mg/m 2 and a latency period of 10 to 40 months which translates to an approximate treatment duration of 12.5 to 37.5 months.Taken together, most reported treatment-related hematological neoplasms appear to develop on or beyond the 12-month mark, while patients are still on treatment with temozolomide. For patients with neuroendocrine neoplasms, where sequencing of multiple therapies is important, we suggest an approach to optimizing treatment duration by establishing disease response at 6 months before continuing further treatment and restricting treatment to or establishing closer vigilance beyond 12 months.

Epstein-barr Virus Negative Primary Central Nervous System Lymphoma Developed after Treatment of Glioblastoma: A Case Report

“… 13 ) According to the study by Park et al, secondary hematological malignancy occurred frequently with a cumulative dose of 18,000 mg/m 2 and within 19 months of treatment duration. 14 ) It is well-known that temozolomide causes lymphopenia as part of myelotoxicity, and previous research indicates that the incidence of severe lymphopenia was 31.6% and that treatment-related lymphopenia is strongly correlated with poor overall survival, low response rate, and recurrences. 15 ) Furthermore, lymphopenia was reported to be a biomarker of impaired host immunity and a decreased low absolute lymphocyte count was a poor prognostic factor for patients with lymphoma and other cancers.…”