Moving forward with actionable therapeutic targets and opportunities in endometrial cancer:NCI clinical trials planning meeting report on identifying key genes and molecular pathways for targeted endometrial cancer trials

The incidence and mortality rates from endometrial cancer are increasing. There have been no new drugs approved for the treatment of endometrial cancer in decades. The National Cancer Institute, Gynecologic Cancer Steering Committee identified the integration of molecular and/or histologic stratification into endometrial cancer management as a top strategic priority. Based on this, they convened a group of experts to review the molecular data in this disease. Here we report on the actionable opportunities and therapeutic directions identified for incorporation into future clinical trials

Randomized Trial of Intravenous Versus Intraperitoneal Chemotherapy Plus Bevacizumab in Advanced Ovarian Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study

PURPOSE: To evaluate the impact of two different intraperitoneal (IP) chemotherapy regimens on progression-free survival (PFS) among women with newly diagnosed advanced ovarian carcinoma. METHODS: Eligible patients were randomly assigned to six cycles of IV paclitaxel 80 mg/m(2) once per week with intravenous (IV) carboplatin area under the curve 6 (IV carboplatin) versus IV paclitaxel 80 mg/m(2) once per week with IP carboplatin area under the curve 6 (IP carboplatin) versus once every 3 weeks IV paclitaxel 135 mg/m(2) over 3 hours day 1, IP cisplatin 75 mg/m(2) day 2, and IP paclitaxel 60 mg/m(2) day 8 (IP cisplatin). All participants received bevacizumab 15 mg/kg IV every 3 weeks in cycles 2 to 22. RESULTS: A total of 1,560 participants were enrolled and had 84.8 months of follow-up. The median PFS duration was 24.9 months in the IV carboplatin arm, 27.4 months in the IP carboplatin arm, and 26.2 months in the IP cisplatin arm. For the subgroup of 1,380 patients with stage II/III and residual disease of 1 cm or less, median PFS was 26.9 (IV-carboplatin), 28.7 (IP-carboplatin), and 27.8 months (IP cisplatin), respectively. Median PFS for patients with stage II/III and no residual disease was 35.9, 38.8, and 35.5 months, respectively. Median overall survival for all enrolled was 75.5, 78.9, and 72.9 months, respectively, and median overall survival for stage II/III with no gross residual disease was 98.8 months, 104.8 months, and not reached. Mean patient-reported Functional Assessment of Cancer Therapy neurotoxicity scores (Gynecologic Oncology Group) were similar for all arms, but the mean Trial Outcome Index of the Functional Assessment of Cancer Therapy-Ovary scores during chemotherapy were statistically worse in the IP cisplatin arm. CONCLUSION: Compared with the IV carboplatin reference arm, the duration of PFS was not significantly increased with either IP regimen when combined with bevacizumab and was better tolerated than IP cisplatin.National Cancer Institute (NCI) [U10 CA180822, U10 CA180868]; NCI [UG1 CA189867]; NSC [704865]; IND [7921]6 month embargo; published online 19 April 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Racial Differences in Clinical Outcomes From Metastatic Breast Cancer: A Pooled Analysis of CALGB 9342 and 9840—Cancer and Leukemia Group B

African American women are more likely to be diagnosed with metastatic breast cancer at the time of presentation than whites, and have shorter survival once diagnosed. This study examines racial differences in clinical outcomes in the setting of two large cooperative group randomized clinical trials

A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.

PURPOSE: Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer. PATIENTS AND METHODS: Patients received either G+C (guadecitabine 30 mg/m2 s.c. once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS). RESULTS: Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs. 9.1 weeks in the G+C and TC groups, respectively; P = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; P = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group. CONCLUSIONS: Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection

Expedition inspiration consensus 2001

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44209/1/10549_2004_Article_357949.pd

Preclinical discovery of candidate genes to guide pharmacogenetics during phase I development: the example of the novel anticancer agent ABT-751

ABT-751, a novel orally available antitubulin agent, is mainly eliminated as inactive glucuronide (ABT-751G) and sulfate (ABT-751S) conjugates. We performed a pharmacogenetic investigation of ABT-751 pharmacokinetics using in-vitro data to guide the selection of genes for genotyping in a phase I trial of ABT-751

VIBRATIONAL SPECTRA OF THE PERFLUOROCYCLOPROPENYL CATION: A POTENTIAL FUNCTION FOR THIS SUBSTANCE AND RELATED CATIONS

$^{1}$ N.C. Craig, R.K.-Y. Lai, L.G. Matus, J.H. Miller, and S.L. Palfrey, J. Am. Chem. Soc. 102, 38 (1980). $^{2}$ N.C. Craig, R.K.-Y. Lai, K.W. Penfield, and I.W. Levin, J. Phys. Chem. 84, 899 (1980).Author Institution: Department of Chemistry, Oberlin CollegeThe perfluorocyclopropenyl cation, $[FIGURE]$, is the product of the reaction of perfluorocyclopropene with Lewis acids, such as $BF_{3}$. From infrared spectra of the solid compounds, $C_{3}F_{3}^{+}BF_{4}^{-}$ and $C_{3}F{_{3}}^{+}SbF{_{6}}^{-}$, and from Raman spectra of $C_{3}F_{3}^{+}BF_{4}^{-}$ in solution in sulfur dioxide we have observed all but one of the spectroscopically active fundamentals of the $C_{3}F_{3}^{+}$ cation which has $D_{3h}$ symmetry. An overlay normal coordinate calculation for the monofluorocation, the $difluoracation,^{2}$ and the perfluorocation has led to a complete assignment of the fundamentals of the $C_{3}F_{3}^{+}$ cation. With calculated values in parentheses this assignment is (in $cm^{-1}$): $(a_{1}') 2013, 751; (a_{2}') (800); (e') (1589, 998, 287; (a_{2}'')(250); (e'') 640$. A discussion will be included of the effect of fluorine substitution on the CC stretching force constants