Adult medulloblastoma: multiagent chemotherapy with cisplatinum and etoposide: a single institutional experience

Abstract

In 1991, a prospective phase II trial was initiated to evaluate the efficacy of treatment for adults with medulloblastoma (MB). After surgery, patients were staged with a neuroradiologic examination of the brain and neuroaxis and by cerebrospinal fluid cytology. All patients received three cycles of upfront cisplatinum (cisplatinum) and etoposide (VP16) chemotherapy followed by cranio-spinal radiation therapy. The current article reports on the long-term results from that trial. After a median follow-up of 14.9 years, among a total of 28 adults with MB, the overall progression-free survival and overall survival (OS) rates at 5 years were 57.6 and 80%, respectively. The median OS for the whole group of patients was 11.3 years. The observed toxicity was mainly hematological, with leukopenia and thrombocytopenia (16% of grades 3 and 4). In summary, in our small series of patients, the role of combination administration of CDDP + VP16 started before the initiation of radiotherapy in reducing recurrences, particularly distant recurrences, remains unclear. To know whether adding chemotherapy to craniospinal radiation in adult therapy increases relapse-free and overall survival, we must await the results of a larger randomized controlled clinical trial.

MiR-584-5p potentiates vincristine and radiation response by inducing spindle defects and DNA damage in medulloblastoma

“…11 ). Since adverse side effects of VCR and IR are also known to be proportional to dosing 11 , 43 , our results suggest that if used as a therapeutic, miR-584-5p not only can inhibit high-risk MB growth but also can lower the VCR and radiation dose (and hence lower the associated toxic effects) required to kill MB cells.…”

“…For example, craniospinal exposure of 35.5 Gy followed by up to 54-Gy radiation boosts to the posterior fossa leads to severe neurocognitive deficits, chronic neuropathy, and chronic hypopituitarism as well as secondary malignancies 8 . Similarly, vincristine (VCR)—a microtubule-interfering chemotherapeutic agent routinely administered as a radiotherapy adjuvant to both high-risk and average-risk MB patients 9 , 10 —causes cumulative dose-dependent neurotoxicity that includes, but is not limited to, sensorimotor and autonomic neuropathy, hearing loss, mononeuropathy, and seizures 11 . Those facts underline the importance of identifying new targets that can serve as more effective and less toxic therapeutics to treat MB.…”

Pleomorphism and drug resistant cancer stem cells are characteristic of aggressive primary meningioma cell lines

“…Cisplatin and etoposide are standard chemotherapeutic agents for many tumors. Both drugs alone, in combination with each other, or in combination with other drugs were found to be effective in adult and pediatric patients with low and high grade gliomas [14–17]. These drugs are not primarily cell cycle affected, thus they could potentially be useful for the slow growing meningioma cells [18].…”

Radiotherapy for adult medulloblastoma: Long term result from a single institution. A review of prognostic factors and why we do need a multi-institutional cooperative program

“…Another Italian prospective study 25 published in 2011 included 28 adult patients treated between 1991 and 2001 with surgery, 3 cycles of upfront chemotherapy with cisplatinum and VP16 followed by craniospinal radiotherapy. Compared to Brandes et al, in this study the patients were treated with the same schedule (CHT + RT) irrespective of their risk class.…”