Feasibility of dasatinib in children and adolescents with new or recurrent central nervous system germinoma

Abstract

Germinomas and embryonal carcinomas are central nervous system (CNS) germ cell tumors (GCT) that may overexpress the proto-oncogene c-KIT, a receptor tyrosine kinase, of which dasatinib is a potent inhibitor. This retrospective review presents the feasibility and tolerability of dasatinib administration in select patients with CNS germinoma. Between November 2008 and April 2010, six patients with newly diagnosed (n = 3) or recurrent (n = 3) CNS GCT were treated in an effort to avoid irradiation and/or delay recurrence. The daily doses administered were 100-170 mg/m(2) with mostly grade 1-2 toxicities. Dasatinib may play a role in future treatment strategies for CNS GCT.

Management of CNS germinoma

“…Dasatinib is a promising medication given its theoretical penetrance of the blood-brain barrier and its known KIT-inhibition. A recent feasibility pilot reviewed the use of Dasatinib in patients with newly diagnosed and recurrent germinoma [33][34][35][36]. No toxicities greater than grade 1 or 2 were reported other than in a patient with grade 3 anemia/neurtropenia in a patient with prior CSI.…”

“Not all that glitters is gold”: insights from the Far East and how to solve a conundrum

“…6 To date, however, studies using imatinib or dasatinb as novel therapeutic agents in progressive or relapsed GCT patients with inhibition of the Kit/Ras/Raf/mitogen-activated protein kinase (MAPK) and/or the Akt1/phosphatidylinositol-3 kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway have yielded disappointing results. 7,8 Using array-comparative genomic hybridization and either whole-exome or targeted sequencing, Takami and colleagues 1 undertook molecular analyses on 123 and 74 of the 190 cases (74 were analyzed for both), respectively. These relatively limited molecular analyses confirmed numerous chromosomal aberrations, some which were found to be independent markers of worse prognosis (2q, 8q gain, 5q, 9p/q, 13q, 15q loss).…”

Reflections on Preventive and Therapeutic Strategies on Metastatic Germinoma in Abdomen: A Case Report and Literature Review

“…For this patient, chemotherapy illustrated excellent therapeutic effect on abdominal germinoma since agents would reach effective plasma concentration much easier in abdomen which lack BBB. Meanwhile, exemption of radiotherapy could also refrain patients from the risk of radiation complications such as enteritis [15].Therefore, chemotherapy with etoposide and platinum comes to the priority and additional choices such as dasatinib, temozolomide and GEMOX (gemcitabine and oxaliplatin) can also be applied [16][17][18]. To date, remedy of agents for treating metastatic germinoma lack a de nite standard, and is probably dependent on factors such as age, serum markers, metastatic sites and sensitivity to platinum.…”