BACKGROUND The primary objective of this study was to evaluate the biochemical effects of gefitinib on its target signal-transduction pathways in patients with recurrent epithelial ovarian cancer ...(EOC). The secondary objectives included assessing clinical activity and toxicity and determining the association between biochemical and clinical outcomes. METHODS Twenty-four heavily pretreated patients with EOC who had good end-organ function and performance status and who had measurable disease received gefitinib 500 mg daily. Prospectively planned core-needle tumor biopsies were obtained before treatment and after 4 weeks. Protein expression of total and phosphorylated (p) epidermal growth factor receptor (EGFR), protein kinase B (AKT), and extracellular regulated kinase (ERK) was quantified in microdissected tumor cells using tissue lysate array proteomics. RESULTS All tumor samples had detectable levels of EGFR and p-EGFR. A decrease in the quantity of both EGFR and p-EGFR was observed with gefitinib therapy in >50% of patients. This was not associated with clinical benefit, nor were responses observed. However, trends for increased gastrointestinal and skin toxicity were observed with greater phosphorylation or quantities of EGFR, ERK, and AKT in tumor samples (P .05). Gefitinib had limited clinical activity as monotherapy despite documented target inhibition. CONCLUSIONS The results from this study demonstrated that gefitinib inhibited the phosphorylation of EGFR in EOC tumor cells, providing proof of target in a clinical setting. Combinatorial therapy with molecular therapeutics against complementary targets may prove successful. Cancer 2007. Published 2007 by the American Cancer Society.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To review the current status of large phase academic clinical trials for women with ovarian cancer, address cross-cutting issues, and identify promising areas for future collaboration.
In May 2009, ...the Gynecologic Cancer Intergroup, which represents 19 Cooperative Groups conducting trials for women with gynecologic cancer, and the US National Cancer Institute convened a Clinical Trials Planning Meeting.
The topics covered included the impact of new developments in cancer biology upon molecular targets and novel agents, pharmacogenomics, advances in imaging, the potential benefit of diet and exercise to reduce the risk of recurrence, academic partnership with industry, statistical considerations for phases 2 and 3 trials, trial end points, and symptom benefit and health-related quality-of-life issues. The clinical trials discussed spanned the spectrum of ovarian cancer from initial diagnosis, staging, and cytoreductive surgery to consolidation chemotherapy, and treatment of recurrent disease.
Ongoing and effective collaboration with industry, government, and patients aims to ensure that the most important scientific questions can be answered rapidly. We encourage women with ovarian cancer and their oncologists to consider participation in the academic clinical trials conducted by the member groups of the Gynecologic Cancer Intergroup.
Determinants of Implementation Effectiveness Helfrich, Christian D; Weiner, Bryan J; McKinney, Martha M ...
Medical care research and review,
06/2007, Volume:
64, Issue:
3
Journal Article
Peer reviewed
Many innovations in the health sector are complex, requiring coordinated use by multiple organizational members to achieve benefits. Often, complex innovations are adopted with great anticipation ...only to fail during implementation. The health services literature provides limited conceptual guidance to researchers and practitioners about implementation of complex innovations. In the present study, we adapt an organizational framework of innovation implementation developed and validated in a manufacturing selling and explore the extent to which it aptly characterizes implementation in health sector organizations. Through comparative case studies of four cancer clinical research networks, we illustrate how this conceptual framework captures key determinants of the implementation of new programs in cancer prevention and control (CP/C) research and helps explain observed differences in implementation effectiveness. Key determinants include management support and innovation-values fit, which contribute to an organizational "climate" for implementation. We explore the implications for researchers and managers. PUBLICATION ABSTRACT
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this ...level may identify cancers earlier than standard 6-12 monthly CA125>35U/mL.
Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject’s baseline, which triggered transvaginal ultrasound. Specificity and PPV were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls.
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