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View the Table of Contents for the September 1 issue of Clinical Cancer Research.
Buckstein et al. Page 5190
Buckstein et al. assessed response, toxicity and biomarkers of angiogenesis to low-dose cyclophosphamide (50 mg orally once daily) and high-dose celecoxib (400 mg orally twice daily) in 32 adult patients with relapsed or refractory aggressive non-Hodgkin’s lymphoma in a multicenter phase II prospective study. The overall best response rate was 37%, and 22% achieved stable disease. The median overall and progression-free survivals were 14.4 and 4.7 months, respectively. Circulating endothelial cells and their precursors (CECs and CEPs) declined in responders. This regimen was well-tolerated palliative chemotherapy and suggests that this combination may be working to inhibit angiogenesis, pending validation in a larger trial.
Lippman et al. Page 5242
Raloxifene, a selective estrogen receptor modulator, has been associated with a reduced risk of breast cancer in postmenopausal women. Lippman et al. explored the effect of up to 8 years of raloxifene on breast cancer risk in postmenopausal women with osteoporosis, grouped by expected risk of breast cancer based on age, age at menopause, body mass index, family history, serum estradiol level, prior estrogen therapy, bone mass/vertebral fracture status, and 5-year predicted risk of breast cancer. Raloxifene therapy was associated with a reduced risk of invasive breast cancer in postmenopausal women irrespective of the presence/absence of risk factors for breast cancer.
Ogura et al. Page 5216
The importance of actin proteins in tumor cells, stromal cells, and peritoneal cells has emerged as a fascinating and somewhat unexpected result of microarray studies. Ogura et al. demonstrated that adenovirus-mediated Calponin h1 (CNh1)-gene therapy against peritoneal dissemination of ovarian cancer is effective bifunctionally—that is, through inhibitory effects on the infected peritoneal cell layers that suppress cancer invasion and, secondly, through direct antitumor effects against invasion and growth properties of cancer cells. Since intraperitoneal administration of CNh1-adenovirus enhanced the therapeutic effect of paclitaxel without an increase in side effects, it appears to be clinically useful, especially in combination with conventional postoperative chemotherapy.
Yee et al. Page 5165
LBH589 is a novel cinnamic hydroxamic acid analog histone deacetylase inhibitor. Yee et al. conducted a Phase I study in patients with refractory hematologic malignancies. LBH589 was administered intravenously as a 30-minute infusion on days 1-7 of a 21-day cycle. Asymptomatic reversible QTcF prolongation was dose-limiting at the 11.5 and 14.0 mg/m2 dose levels. In 8 of 11 patients with peripheral blasts, transient reductions occurred with a rebound following the 7-day treatment period, and significant acetylation increases were observed in some cells, including B-cells and blasts. The consistent transient antileukemic and biologic effects observed encourage the development of an oral LBH589 preparation.