Tenofovir disoproxil fumarate discontinuation for renal outcomes: any room for treatment personalization?

Tenofovir disoproxil fumarate (TDF) is a very effective antiviral drug that has been associated with tubular dysfunction. The aim of this study was to analyze the demographic, pharmacokinetic, and pharmacogenetic variables associated with TDF discontinuation for renal outcomes in stable HIV-positive patients using multivariable analyses. Three hundred and four patients were included (73% male, with median age and eCrCl of 45.3 years and 90.9 mL/min, respectively). After a median follow-up of 28.3 months, 27 patients discontinued TDF for renal adverse events [persistent urinary abnormalities (n = 21) or eCrCl < 60 mL/min (n = 6)] providing an incidence of 3.77 events per 100 patient-year. The probability of TDF discontinuation was higher with several features (male gender, older age, not Caucasians ancestry, absence of intravenous drug abuse, protease inhibitors, previous indinavir, HCV-positivity, lower CD4 cell count, detectable HIV-RNA, lower eCrCl, spot-urine proteinuria) and higher tenofovir concentrations but not genetic variants. Tenofovir plasma concentrations were prognostic of TDF discontinuation for renal adverse events suggesting that dose-adjustment may be warranted for long-term safety.

DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) is an effective regimen for peripheral blood stem cell collection in multiple myeloma.

DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) has proved to be an effective salvage therapy for refractory-relapsed MM patients. Little is known, however, about its potential as mobilizing therapy. The aim of this study was to evaluate the efficacy of DCEP in mobilizing PBSC and to define its toxicity. Fifty-five MM patients received DCEP followed by G-CSF as part of high-dose programs including autologous transplantation. At the time of mobilization, 40 patients had previously received VAD only, and 15 alkylating agents. Mobilization was successful (minimum number of CD34(+) cells 2 x 10(6)/kg) in 48/55 patients (87%), and 41/55 patients (75%) collected >4 x 10(6)/kg CD34(+) cells. Of the seven patients who did not mobilize stem cells, five (71%) had been previously exposed to alkylating agents. The median number of CD34(+) cells harvested was 5.8 x 10(6)/kg (range 2.1-22.4). There was no treatment-related mortality. The side-effects of DCEP were always tolerable. No neutropenia <1000/microl nor thrombocytopenia <50,000/microl were observed. No patient required transfusion as a consequence of therapy, or hospitalization for septic complications. In conclusion, DCEP, in addition to its demonstrated anti-tumor activity, is an effective regimen for mobilizing peripheral blood progenitor cells in myeloma patients, with little or no side-effects. These properties render DCEP a useful regimen for the debulking and mobilization phase of high-dose programs for multiple myeloma.

[Acute cardiotoxicity from 5-fluorouracil: un underestimated toxicity]. / Cardiotossicità acuta da 5-fluorouracile: una tossicità sottovalutata.

The most common toxicity in clinical trials with 5-FU, in mono or polychemotherapy, is stomatitis, diarrhea, hand-foot syndrome. In this case report, the 5-fluorouracil (5-FU) cardiotoxicity, an uncommon 5-FU-related toxicity, has been investigated. Cardiotoxicity reports are uncommon because the problem is not well known. This study is also a review of the recent literature and it recommend to take care in prescribing chemotherapy to patients with heart disease history.

[Effects of PGE1 (alprostadil alpha-cyclodestrin) in a case of probable paraneoplastic thrombocytopenic purpura]. / Effetti della PGE1 (alprostadil alpha-ciclodestrina) in un caso di porpora trombocitopenica verosimilmente paraneoplastica.

The authors report the case of a severely vasculopathic patient with pulmonary mediastinal tumour who presented, probably on a paraneoplastic basis, the onset of severe thrombocytopenic purpura persisting for several months. The syndrome was not classifiable in any of the forms known to the authors and was completely resolved by treatment with PGE1 (alprostadil-alpha-cyclodextrine (Prostavasin, Schwarz Pharma).