BJMO - volume 11, issue 6, october 2017
P. Frères MD, C. Gennigens MD, PhD, D. Martin MD, PhD, G. Jerusalem MD, PhD
Leptomeningeal carcinomatosis (LC), or neoplastic meningitis, is a disastrous complication of advanced cancer. This disease occurs in approximately 5% of patients with solid tumour and results from the dissemination of tumour cells from the cerebral spinal fluid (CSF) flow throughout the entire central nervous system (CNS). LC is characterized by multiple and fluctuant neurologic symptoms and signs. Useful tests for the diagnosis include magnetic resonance imaging (MRI) and CSF analysis. Unfortunately, the diagnosis remains challenging due to pleomorphic symptoms and false negative results of diagnostic procedures. For most patients, the aim of the treatment is to control symptoms, by using targeted radiotherapy and corticosteroids. More aggressive therapeutic approaches, such as intrathecal (IT) or systemic chemotherapy, should be restricted to highly selected and good-risk patients. Moreover, only few randomized clinical trials are available in the field and studies using more recent targeted therapies or immunotherapy should always be considered in these patients, as outcome with standard of care is disappointing.
(BELG J MED ONCOL 2017;11(6):259–264)Read more
BJMO - volume 10, issue 4, july 2016
P. Frères MD, L. Lousberg MD, G. Jerusalem MD, PhD
Dysregulation of the cell cycle is a classic hallmark of cancer. Cell cycle control by the inhibition of cyclin-dependent protein kinases represents new options for anticancer therapy. Abemaciclib (LY2835219), ribociclib (LEE011) and palbociclib (PD0332991) are selective oral inhibitors of CDK4/6 and are largely under evaluation in clinical trials in the field of breast cancer. In an open-label, randomised phase II study (PALOMA-1/TRIO-18 trial), the combination of palbociclib and letrozole, compared to letrozole alone, significantly prolongs progression-free survival of patients suffering from ER positive HER2 negative advanced breast cancer and who had not received any systemic treatment for their advanced disease. More recently, it has also been shown that palbociclib combined with fulvestrant resulted in longer progressionfree survival than fulvestrant alone in patients presenting ER positive HER2 negative advanced breast cancer and who had progression of disease during endocrine therapy. The toxicity profile of palbociclib is manageable. The most common grade 3 or 4 adverse events include neutropenia, anaemia, thrombocytopenia and fatigue. Toxicity related permanent discontinuation is unusual. Additional phase III data evaluating CDK4/6 inhibitors in patients with endocrine sensitive disease or after failure of previous endocrine therapy are expected in the very near future. Impact of CDK4/6 inhibitors on overall survival and the role of CDK4/6 inhibitors in the adjuvant or neoadjuvant setting are under evaluation. More treatment options are now evaluable for patients with ER positive HER2 negative advanced breast cancer. Optimal sequence of the available therapies remains unknown. Unfortunately, no trials have been designed to answer this important question.
(BELG J MED ONCOL 2016;10(4):132–138)Read more