Endothelial and Astrocytic Support by Human Bone Marrow Stem Cell Grafts into Symptomatic ALS Mice towards Blood-Spinal Cord Barrier Repair.

Vascular pathology, including blood-CNS barrier (B-CNS-B) damage via endothelial cell (EC) degeneration, is a recently recognized hallmark of Amyotrophic Lateral Sclerosis (ALS) pathogenesis. B-CNS-B repair may be a new therapeutic approach for ALS. This study aimed to determine effects of transplanted unmodified human bone marrow CD34+ (hBM34+) cells into symptomatic G93A mice towards blood-spinal cord barrier (BSCB) repair.

The interactions of anti-cancer drugs approved in the last decade in the United States with membrane transporters.

Membrane transporters play a role in determining the absorption, distribution, metabolism and excretion of small molecule anticancer drugs and mediating chemosensitivity and resistance of tumor cells to these drugs. Our understanding of the influence of these transporters on the pharmacokinetics, clinical effectiveness and tolerability has considerably increased in the last decade. Therefore, determining the interaction of membrane transporters with small molecule anticancer drugs can facilitate the development of effective and safe treatments.

New era in drug interaction evaluation: US Food and Drug Administration update on CYP enzymes, transporters, and the guidance process.

Predicting clinically significant drug interactions during drug development is a challenge for the pharmaceutical industry and regulatory agencies. Since the publication of the US Food and Drug Administration's (FDA's) first in vitro and in vivo drug interaction guidance documents in 1997 and 1999, researchers and clinicians have gained a better understanding of drug interactions. This knowledge has enabled the FDA and the industry to progress and begin to overcome these challenges.

Vorinostat for treatment of cutaneous manifestations of advanced primary cutaneous T-cell lymphoma.

Purpose: To discuss vorinostat approval for treatment of cutaneous manifestations of advanced cutaneous T-cell lymphoma (CTCL).

Experimental Design: Data from 1 single-arm, open-label, multicenter pivotal trial and 11 other trials submitted to support the new drug application for vorinostat in the treatment of advanced primary CTCL were reviewed. The pivotal trial assessed responses by changes in overall skin disease score using a severity-weighted assessment tool (SWAT).

Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma.

Purpose: To describe the Food and Drug Administration (FDA) review and approval of sunitinib malate (Sutent). Sunitinib received regular approval for the treatment of gastrointestinal stromal tumor (GIST) after disease progression or intolerance to imatinib mesylate (Gleevec). Additionally, sunitinib received accelerated approval for the treatment of advanced renal cell carcinoma.

Topotecan in combination with cisplatin for the treatment of stage IVB, recurrent, or persistent cervical cancer.

Purpose: Topotecan, a camptothecin analog previously approved for the treatment of ovarian cancer and small-cell lung cancer, was granted regular approval by the US Food and Drug Administration (FDA) on June 14, 2006, for use in combination with cisplatin to treat women with stage IVB, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment with surgery and/or radiation therapy. The purpose of this summary is to review the database supporting this approval.

Experimental Design: In a randomized multicenter study enrolling 293 eligible patients, topotecan plus cisplatin (TC) was compared with cisplatin monotherapy.

Approval summary: nelarabine for the treatment of T-cell lymphoblastic leukemia/lymphoma.

Purpose: To describe the clinical studies, chemistry manufacturing and controls, and clinical pharmacology and toxicology that led to Food and Drug Administration approval of nelarabine (Arranon) for the treatment of T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma.

Experimental Design: Two phase 2 trials, one conducted in pediatric patients and the other in adult patients, were reviewed. The i.

Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes.

Purpose: This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome.

Approval summary: Docetaxel in combination with prednisone for the treatment of androgen-independent hormone-refractory prostate cancer.

Purpose: Docetaxel, a taxane previously approved for the treatment of breast cancer and non-small cell lung cancer, was approved by the United States Food and Drug Administration on May 19, 2004 for use in combination with prednisone for the treatment of metastatic androgen-independent (hormone-refractory) prostate cancer. The purpose of this summary is to review the database supporting this approval.

Experimental Design: In a randomized, global study enrolling 1,006 patients, two schedules of docetaxel were compared with mitoxantrone + prednisone as follows: MTZ q 3w, mitoxantrone 12 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; TXT q 3w, docetaxel 75 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; and TXT qw, docetaxel 30 mg/m2 days 1, 8, 15, 22, and 29 every 6 weeks + prednisone 5 mg twice a day for a total of 5 cycles.

United States Food and Drug Administration Drug Approval summary: Gefitinib (ZD1839; Iressa) tablets.

On May 5, 2003, gefitinib (Iressa; ZD1839) 250-mg tablets (AstraZeneca Inc.) received accelerated approval by the United States Food and Drug Administration as monotherapy for patients with locally advanced or metastatic non-small cell lung cancer after failure of both platinum-based and docetaxel chemotherapies. Information provided in this summary includes chemistry manufacturing and controls, clinical pharmacology, and clinical trial efficacy and safety results.