Drug and Alcohol Rehabilitation: Brentuximab Vedotin.

Brentuximab vedotin.

Filed under: Drug and Alcohol Rehabilitation

Clin Cancer Res. 2012 Nov 15;
Deng C, Pan B, O’Connor OA

Brentuximab vedotin (SGN-35), an intravenously administered CD30-specific antibody-drug conjugate, has recently been approved by the U.S. Food and Drug Administration for two indications, including (1) patients with Hodgkin’s lymphoma (HL) relapsing after autologous stem cell transplantation (ASCT), or after two multi-drug regimens in HL patients who are not candidates for ASCT; and (2) patients with systemic anaplastic large cell lymphoma (ALCL) who failed at least one prior multi-drug chemotherapy regimen. HL and ALCL patients treated with brentuximab vedotin demonstrated markedly high response rates for a single agent, exceeding 70% and 80% for HL and ALCL, respectively. The complete response rate was equally as impressive, at 34% and 57% for HL and ALCL, respectively. These and results from many upcoming clinical trials, where brentuximab vedotin is being investigated in the frontline setting, promise to profoundly change how we manage the CD30 positive lymphoproliferative malignancies. The mechanism of action, preclinical antitumor activity, and clinical activity of brentuximab vedotin against HL, ALCL, and other CD30 expressing lymphoma are reviewed.
HubMed – drug

Targeted Delivery of Paclitaxel to EphA2-Expressing Cancer Cells.

Filed under: Drug and Alcohol Rehabilitation

Clin Cancer Res. 2012 Nov 15;
Wang S, Noberini R, Stebbins JL, Das SK, Zhang Z, Wu B, Mitra S, Billet S, Fernandez A, Bhowmick NA, Kitada S, Fisher P, Pasquale EB, Pellecchia M

PURPOSE: YSA is an EphA2-targeting peptide that effectively delivers anti-cancer agents to prostate cancer tumors (1). Here, we report on how we increased the drug-like properties of this delivery system. EXPERIMENTAL DESIGN: By introducing non-natural amino acids, we have designed two new EphA2 targeting peptides: YNH, where norleucine and homoserine replace the two methionine residues of YSA, and dYNH, where a D-tyrosine replaces the L-tyrosine at the first position of the YNH peptide. We describe the details of the synthesis of YNH and dYNH paclitaxel conjugates (YNH-PTX and dYNH-PTX) and their characterization in cells and in vivo. RESULTS: dYNH-PTX showed improved stability in mouse serum and significantly reduced tumor size in a prostate cancer xenograft model and also reduced tumor vasculature in a syngeneic orthotopic allograft mouse model of renal cancer compared to vehicle or paclitaxel treatments. CONCLUSION: This study reveals that targeting EphA2 with dYNH drug conjugates could represent an effective way to deliver anti-cancer agents to a variety of tumor types. Translational Relevance: Overexpression of the EphA2 positively correlates with tumor malignancy and poor prognosis. For this reason, EphA2 is an attractive target for cancer cell specific drug delivery. In this study, we report on the development of dYNH, an EphA2 targeting peptide that when coupled to paclitaxel (PTX) has favorable pharmacological properties and possesses powerful anti-tumor activity in vivo. dYNH-PTX may allow for an expanded therapeutic index of paclitaxel as well as precluding the need for complex formulations and long infusion times.
HubMed – drug

Pharmacokinetic Interactions Between the HCV Protease Inhibitor Boceprevir and Ritonavir-Boosted HIV-1 Protease Inhibitors Atazanavir, Darunavir, and Lopinavir.

Filed under: Drug and Alcohol Rehabilitation

Clin Infect Dis. 2012 Nov 15;
Hulskotte EG, Feng HP, Xuan F, van Zutven MG, Treitel MA, Hughes EA, O’Mara E, Youngberg SP, Wagner JA, Butterton JR

Background.?Boceprevir represents a new treatment option for hepatitis C (HCV)-infected patients, including those with HCV/human immunodeficiency virus (HIV) coinfection; however, little is known about pharmacokinetic interactions between boceprevir and antiretroviral drugs.Methods.?A randomized, open-label study to assess the pharmacokinetic interactions between boceprevir and ritonavir-boosted protease inhibitors (PI/r) was conducted in 39 healthy adults. Subjects received boceprevir (800 mg, three times daily) for 6 days and then received PI/r as follows: atazanavir (ATV) 300 mg once daily, lopinavir (LPV) 400 mg twice daily, or darunavir (DRV) 600 mg twice daily, each with ritonavir (RTV) 100 mg on days 10-31, plus concomitant boceprevir on days 25-31.Results.?Boceprevir decreased the exposure of all PI/r, with AUC(0-last) geometric mean ratios (GMR [90% confidence interval]) of 0.65 (0.55-0.78) for ATV/r; 0.66 (0.60-0.72) for LPV/r, and 0.56 (0.51-0.61) for DRV/r. Coadministration with boceprevir decreased RTV AUC(?) by 22%-36%. ATV/r did not significantly affect boceprevir exposure, but boceprevir AUC(?) was reduced by 45% and 32% when coadministered with LPV/r and DRV/r, respectively. Overall, treatments were well tolerated with no unexpected adverse events.Conclusions.?Concomitant administration of boceprevir with PI/r resulted in reduced exposures of PI and boceprevir. These drug-drug interactions may reduce the effectiveness of PI/r and/or boceprevir when coadministered.
HubMed – drug

Dick Batchelor – Social-service workers, clients rally to decry funding cuts – Dozens of social-service workers and their clients rallied in Orlando on Friday to warn of “Draconian” legislative cuts targeting state-funded programs for mental health , drug and alcohol rehabilitation, foster children and those with disabilities… www.orlandosentinel.com

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