Bortezomib-induced skin eruption

Bortezomib (Velcad) is a proteasome inhibitor recently developed and mainly used for the treatment of multiple myeloma. Bortezomib represents a novel class of drugs functioning as proteasome inhibitors. Skin complications of bortezomib treatment are very frequent but poorly characterized. We describe the case of a patient who developed erythematous and edematous plaques after treatment with bortezomib. This case illustrates one of the potential reactions associated with bortezomib administration and underlines the need to recognize and report cutaneous side effects of this new drug

Etude de l'activité antifongique in vitro d'une suspension à base de nystatine destinée aux soins de bouche de patients cancéreux = Potency assay in vitro of fungistatical preparations with nystatin for mouthcare of cancer patients

Le muguet est une affection fréquente chez les patients cancéreux. Elle influence négativement la qualité de vie du patient en rendant difficile l'acte de manger et de parler. Une suspension pour les soins de bouche, à base de nystatine et vitamines, est utilisée dans nos hôpitaux sous le nom de « suspension CESCO »: elle a donné des résultats cliniquement intéressants en prévenant ou en diminuant l'infection mycosique. Dans ce travail sont rapportés les résultats d'une étude de l'activité antifongique in vitro de notre préparation. Des échantillons de cette suspension ont été stockés à 4 °C pendant un mois durant lequel l'activité antifongique sur Candida albicans et Saccharomyces cerevisiae a été testée une fois par semaine après dissolution dans du diméthylformamide (DMF). Étonnamment, l'activité de la suspension augmente pendant les deux premières semaines de stockage. Pendant cette période, on a également noté que l'activité d'une concentration de 100 UI/ml était supérieure à celle de 180 UI/ml. Nous émettons l'hypothèse que les différentes vitamines présentes dans la suspension agissent soit en neutralisant la nystatine (vitamines B 1 , B2, B6 et C), soit, au contraire, en protégeant l'antibiotique d'une oxydation (vitamines A, C et E). Ces vitamines se dégradent à des vitesses différentes, ce qui induit les variations au niveau de l'activité antifongique de la nystatine. Toutefois, ces variations d'activité restent de faible amplitude jusqu'à 21 jours de stockage. En pratique, les suspensions aqueuses utilisées ne contiennent gu'une faible fraction de nystatine dissoute. Testés in vitro, sans solubilisation par le DMF, tous les échantillons de la suspension ont manifesté une activité fongistatique similaire à l'égard de Candida albicans. L'action fongicide est faible, mais elle augmente lors de contacts répétés entre les levures et la suspension (ce qui éguivaudrait à prolonger le temps de contact). Ces résultats semblent çonfirmer l'observation clinique qu'un rinçage fréquent et régulier de la cavité buccale est efficace dans la prévention du muguet. Une formule galénique permettant de prolonger le contact entre la nystatine et les muqueuses pourrait apporter un bénéfice supplémentaire

Les bisphosphonates en oncologie: incertitudes et controverses en 2007 [Bisphosphonates in oncology: update 2007]

Bisphosphonates prevent bone complications induced by cancer. Their low toxicity promoted their extensive use supported by different international recommendations. However the prescription of these therapies is now seriously questioned because of their late and severe toxicity, the osteonecrosis of the jaw, and the growing efficiency of the oncologic therapies. No monitoring method is now available for bisphosphonates therapy. Therefore only a stricter selection of the patients, based on established and well-proven indications, as well as limitation of the administration durations could maintain an adequate risk/benefit ratio

A Multi-Center Phase II Study (SAKK 36/06) of Single Agent Everolimus (RAD001) In Patients with Relapsed or Refractory Mantle Cell Lymphoma

Introduction: Mantle cell lymphoma (MCL) accounts for 6% of all B-cell lymphomas and remains incurable for most patients. Those who relapse after first line therapy or hematopoietic stem cell transplantation have a dismal prognosis with short response duration after salvage therapy. On a molecular level, MCL is characterised by the translocation t[11;14] leading to Cyclin D1 overexpression. Cyclin D1 is downstream of the mammalian target of rapamycin (mTOR) kinase and can be effectively blocked by mTOR inhibitors such as temsirolimus. We set out to define the single agent activity of the orally available mTOR inhibitor everolimus (RAD001) in a prospective, multi-centre trial in patients with relapsed or refractory MCL (NCT00516412). The study was performed in collaboration with the EU-MCL network. Methods: Eligible patients with histologically/cytologically confirmed relapsed (not more than 3 prior lines of systemic treatment) or refractory MCL received everolimus 10 mg orally daily on day 1 - 28 of each cycle (4 weeks) for 6 cycles or until disease progression. The primary endpoint was the best objective response with adverse reactions, time to progression (TTP), time to treatment failure, response duration and molecular response as secondary endpoints. A response rate of 10% was considered uninteresting and, conversely, promising if 30%. The required sample size was 35 pts using the Simon's optimal two-stage design with 90% power and 5% significance. Results: A total of 36 patients with 35 evaluable patients from 19 centers were enrolled between August 2007 and January 2010. The median age was 69.4 years (range 40.1 to 84.9 years), with 22 males and 13 females. Thirty patients presented with relapsed and 5 with refractory MCL with a median of two prior therapies. Treatment was generally well tolerated with anemia (11%), thrombocytopenia (11%), neutropenia (8%), diarrhea (3%) and fatigue (3%) being the most frequent complications of CTC grade III or higher. Eighteen patients received 6 or more cycles of everolimus treatment. The objective response rate was 20% (95% CI: 8-37%) with 2 CR, 5 PR, 17 SD, and 11 PD. At a median follow-up of 6 months, TTP was 5.45 months (95% CI: 2.8-8.2 months) for the entire population and 10.6 months for the 18 patients receiving 6 or more cycles of treatment. Conclusion: This study demonstrates that single agent everolimus 10 mg once daily orally is well tolerated. The null hypothesis of inactivity could be rejected indicating a moderate anti-lymphoma activity in relapsed/refractory MCL. Further studies of either everolimus in combination with chemotherapy or as single agent for maintenance treatment are warranted in MCL

A multicenter phase II study (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma

Introduction: Mantle cell lymphoma (MCL) accounts for 6% of all B-cell lymphomas and is in most cases an incurable disease. It is characterized by the translocation t(11;14) leading to Cyclin D1 over-expression. Cyclin D1 is downstream of the mammalian target of rapamycin (mTOR) threonine kinase and can be effectively blocked by mTOR inhibitors. We set out to define the single agent activity of the orally available mTOR inhibitor everolimus in a prospective, multicentre trial in patients with relapsed or refractory MCL (NCT00516412).Methods: Eligible patients with confirmed relapsed or refractory MCL received everolimus 10 mg for 28 days (one cycle) for a total of 6 cycles or until disease progression. The primary endpoint was the best objective response (OR) with adverse reactions, time to progression (TTP), time to treatment failure, response duration and molecular response as secondary endpoints.Results: A total of 36 patients with 35 evaluable patients at a median age of 69 years (range 40 to 85 years) from 19 centers were enrolled between August 2007 and January 2010. Treatment was generally well tolerated with anemia (11%), thrombocytopenia (11%), neutropenia (8%), diarrhea (3%) and fatigue (3%) being the most frequent complications of CTC grade 3 or higher. The OR rate was 20% (95% CI: 8-37%) with 2 complete remissions (CR) and 5 partial response (PR), stable disease (SD) 48% and progression disease (PD) 28%. At a median follow-up of 6 months, TTP was 5.45 months (95% CI: 2.8-8.2 months) for the entire population and 10.6 months for the 18 patients receiving 6 or more cycles of treatment. Three patients achieved a lasting complete molecular response when assessed in the peripheral blood.Conclusion: This study demonstrates that single agent everolimus is well tolerated and has anti-lymphoma activity including lasting molecular responses. Further studies of everolimus either in combination with chemotherapy or as single agent for maintenance treatment are warranted in MCL