29.09.2015

Ovarian cancer clinical trials md anderson

Vaccine Delays Recurrence in Ovarian Cancer: In a phase II open-label clinical trial, maintenance therapy with Vigil, an autologous tumor cell vaccine, resulted in a delay in disease progression in late-stage ovarian cancer patients. Bevacizumab Added to Chemotherapy Improves Progression-Free Survival in Ovarian Cancer: The Gynecologic Oncology Group 213 trial demonstrated that adding bevacizumab to paclitaxel and carboplatin improved progression-free survival in 674 women with recurrent, platinum-sensitive ovarian cancer. Olaparib Beneficial in Heavily Pretreated Advanced Ovarian Cancer Patients With BRCA Mutations: A pooled analysis from six prospective clinical trials found that patients with relapsed ovarian, fallopian tube, or peritoneal cancer with germline BRCA mutations had a 36% overall response rate with olaparib monotherapy. Varying Ovarian Cancer Survival Outcomes Among Asian and Caucasian Patients: Asians enrolled in phase III epithelial ovarian cancer clinical trials had prolonged survival compared with Caucasian patients. High Pretreatment Circulating Tumor Cell (CTC) Count Associated With Higher Survival in Cervical Cancer: Advanced cervical cancer patients who had higher numbers of CTCs prior to treatment with chemotherapy plus bevacizumab in the Gynecologic Oncology Group 240 phase III clinical trial had higher overall survival.
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Each year, more than 91,700 new cases of gynecologic malignancies are diagnosed in the United States, and more than 28,000 women lose their lives to gynecologic cancer.[1] Until recently, treatment paradigms in gynecologic oncology have mainly included a combination of radical surgery, cytotoxic chemotherapy (CT), and radiation therapy. The past year saw the approval of the humanized anti-VEGF antibody bevacizumab for two indications in gynecologic oncology.
In the last 8 decades, theories regarding carcinogenesis have progressed to include numerous pathways by which cells achieve immortality. Angiogenesis has been studied in depth, with the VEGF pathway having received the most attention because of its central role in regulation. Platelet-derived growth factor (PDGF) and FGF are parts of another key regulatory pathway in angiogenesis.
The epidermal growth factor (EGF) pathway is another potential target in the angiogenesis pathway. The Src nonreceptor kinase family directly interfaces with the VEGF axis and plays an important role in cell adhesion and survival in both normal cells and cancer cells. Finally, vascular disrupting agents (VDA), a class of tubulin destabilizers and flavonoids, are some of the newest non-chemotherapeutic options; VDAs target aberrant vascularization and are being studied in the setting of ovarian cancer.
For instance, she and her team have always known the immune system was a primary line of defense against infections, viruses, parasites and the like. Panos Konstantinopoulos, MD, PhDDana-Farber Cancer Institute scientists have shed new light on why some ovarian cancers don’t respond to or learn to evade standard chemotherapy and targeted drugs. Ovarian Cancer Research Fund (OCRF) and the Ovarian Cancer National Alliance (OCNA) have led the way in advocacy, research and support for patients and their families for over 22 years.
We wish everyone going through this terrible illness courage, determination, conviction and hope.
The trial included 31 patients who either received the vaccine (n = 20) or did not (n = 11).
The 273 patients included in the analysis had all been previously treated with chemotherapy. Bevacizumab was recently approved for use in advanced cervical cancer and platinum-resistant ovarian cancer. Angiogenesis, the recruitment of new blood vessels from the pre-existing vascular matrix, is now a well-established prerequisite for tumor progression.
In August 2014, the US Food and Drug Administration (FDA) approved bevacizumab for the treatment of advanced cervical cancer, the first gynecologic cancer for which an anti-angiogenic agent has demonstrated an advantage in overall survival (OS).


However, multiple pathways are currently under investigation and hold tremendous promise for the future treatment of gynecologic malignancies (Figure 1). Experiments with c-MET inhibition in vivo have been shown to decrease peritoneal dissemination of ovarian cancer cells and to inhibit ascites formation.[19] Rilotumumab, a monoclonal HGF antibody, is currently undergoing phase II investigation for recurrent EOC (NCT01039207). The downstream effects of Eph receptor signaling include activation of integrins and other focal adhesion–associated proteins. Notch proteins are cell surface protein receptors normally involved in transmitting growth signals to those cells undergoing physiologic cell fate changes. Everolimus, an mTOR inhibitor, has been studied in multiple phase II trials in gynecologic malignancies. While agents like bevacizumab target the recruitment of new vasculature to the periphery of tumors, VDAs act at the level of endothelial cells to limit tumor perfusion, causing tumor necrosis from within. The talent of these teams is unmatched, and among the many reasons they’re leading the charge to end cancer globally. Their position was to help the immune system recognize cancer in the body where it shouldn’t be, and then mount a response specific to that cancer. They help fuel our research, clinical trials and treatment breakthroughs for millions of patients. As of January 2016, we are pleased to announce we are joining together to form Ovarian Cancer Research Fund Alliance (OCRFA), the largest global organization dedicated to advancing ovarian cancer research while supporting women and their families. The overall survival advantage bevacizumab confers in advanced cervical cancer prompted a paradigm shift in the standard of care for this disease. Growth factors such as fibroblast growth factor (FGF), vascular endothelial cell growth factor (VEGF), and angiopoietin-1 (Ang1) are upregulated to stimulate angiogenesis, while downregulation of endogenous protein inhibitors (thrombospondin 1 and interferon) disrupts the balance of physiologic angiogenesis.
In November 2014, recurrent platinum-resistant ovarian cancer became an approved indication for bevacizumab. Although a specific role in carcinogenesis has not been clarified, the role of Eph receptors in intercellular communication is likely their contribution to the cancer–somatic cell interface of the tumor microenvironment and represents another potential therapeutic target. In the angiogenic cancer microenvironment, they have been associated with vessel maturation, pericyte recruitment, and vascular branching.
Results from Gynecologic Oncology Group (GOG) 186I (NCT01305213), a phase II trial utilizing the VDA fosbretabulin tromethamine in combination with bevacizumab in patients with recurrent or persistent ovarian cancer, were recently presented at the International Gynecologic Cancer Society 2014 Annual Meeting.
Because such tumors can’t repair damage to their DNA effectively, are vulnerable to platinum-based chemotherapy agents and newer targeted drugs called PARP inhibitors that shred the tumors’ DNA molecules.While these drugs are often effective, a substantial number of patients don’t respond to them or become resistant to the drugs, reducing their long-term survival.
Within the group of patients treated with bevacizumab, the hazard ratio (HR) for death for pre-treatment CTC counts was 0.9. Because many other therapeutic options are available, and because of the heterogeneity of ovarian malignancies, the best combination of chemotherapeutics and bevacizumab has yet to be determined; studies are on-going. These events are influenced by and activate other molecular pathways, including phosphatidylinositol 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK),[2] and therapies are now available that target these pathocellular processes.
Cervical and ovarian carcinogenesis employ different pathways to achieve cellular immortalization, and this has a significant bearing on the evidence supporting the use of anti-angiogenic agents in the two malignancies.
Trebananib plus carboplatin and paclitaxel chemotherapy (CT) as first-line treatment for advanced ovarian cancer is currently being evaluated in TRINOVA-3 (NCT01493505), which recently closed to accrual. A small-molecule inhibitor of VEGFR and EGFR, vandetanib, was created to address EGFR-mediated anti-VEGF resistance and is currently under investigation in combination with docetaxel for recurrent ovarian cancer (NCT00872989).


The Notch pathway has also been implicated in the physiologic response to loss of VEGF signaling, and thus may participate in tumor adaptation to VEGF inhibitors.[21,22] Currently, a phase II trial evaluating RO4929097, an oral gamma secretase inhibitor, is being evaluated in platinum-resistant recurrent ovarian cancer (NCT01175343). It was these other malignancies, like lung, breast, and ovarian, that really helped them hone in on directing the immune system to fight cancer. One way that BRCA1 and 2 -mutant ovarian tumors outwit treatment is by gaining additional mutations that restore their molecular DNA-repair pathways.In the new research, however, senior authors Dipanjan Chowdhury, PhD and Panos Konstantinopoulos, MD, PhD of Dana-Farber Cancer Institute discovered a different resistance mechanism that that doesn’t involve acquiring new mutations. The plan was for her to do six rounds, then a final high dose round before undergoing a stem-cell transplant.
The utility of bevacizumab in uterine cancer has not been consistently demonstrated; current studies are limited to early-phase clinical trials.
The use of anti-angiogenesis in uterine cancer is currently still undergoing more basic investigation, with clinical trials in earlier stages.
A combined approach using inhibition of both Notch and VEGF may hold promise in the future treatment of patients with gynecologic cancers. The avoidance of side effects commonly associated with cytotoxic chemotherapy makes this an attractive alternative for this patient population. Instead, the ovarian cancer cells turn off one of two competing DNA repair pathways and turn on another pathway, known as homologous recombination (HR) that enables the tumor to resist platinum drugs and PARP inhibitors. Other anti-angiogenic agents, including oral therapies for cervical and ovarian cancers, are under investigation; this therapeutic class of drugs appears promising. The purpose of this paper is to provide a review of site-specific treatment options that involve the targeting of angiogenesis in gynecologic malignancies.
However, in November, she began getting sicker and sicker and it was discovered the cancer had returned to her abdomen. A phase III randomized controlled clinical trial of carboplatin and paclitaxel alone or in combination with bevacizumab followed by bevacizumab and secondary cytoreductive surgery in platinum-sensitive, recurrent ovarian, peritoneal primary and fallopian tube cancer (Gynecologic Oncology Group 0213).
Next, they looked for an association between increased levels of miR-622 and outcomes of ovarian cancer patients represented in a database compiled by The Cancer Genome Atlas project (TGCA). We took her by medivac to MD Anderson Cancer Center in Houston in hopes of undergoing a surgery there to remove the new cancer and have heated chemotherapy administered directly to her abdomen.
Instead, they’re believed to belong to an ancient system for regulating genes in plants and animals.
The human genome contains an estimated 2,500 miRNAs, whose importance only became clear beginning in the early 2000s. Moreover, “miR-622 may be a promising target for augmenting response to PARP inhibitors and platinum chemotherapy for these tumors,” according to the researchers.Konstantinopoulos is a medical oncologist in the Susan F. Smith Center for Women’s Cancers at Dana-Farber, and Chowdhury is in the department of radiation oncology at Dana-Farber.First author is Young Eun Choi is a postdoctoral fellow in the Chowdhury laboratory. Funding for study comes from Department of Defense Ovarian Cancer Academy Award W81XWH-10-1-0585, NCI grant R01CA142698-07 and the Deborah and Robert First Foundation. Differences in presentation and survival of Asians versus Caucasians with ovarian cancer: A Gynecologic Oncology Group ancillary study of 7914 patients.



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