Counterpoint: Chemosensitivity Assays for Recurrent Ovarian Cancer

2011 ◽  
Vol 9 (1) ◽  
pp. 121-124 ◽  
Author(s):  
Maurie Markman
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Recurrent Ovarian Cancer ◽  
Evidence Based ◽  
Chemosensitivity Assay ◽  
Reliable Evidence ◽  
In Vitro Chemosensitivity ◽  
Frequent Use ◽  
Chemosensitivity Assays

Unfortunately, no reliable evidence-based data have shown any in vitro chemosensitivity assay strategy to be clinically useful in the management of recurrent ovarian cancer, despite frequent use. Several clinical trials have been proposed with the potential to support or refute the relevance of these approaches.

scholarly journals Point: Chemosensitivity Assays Have a Role in the Management of Recurrent Ovarian Cancer

2011 ◽  
Vol 9 (1) ◽  
pp. 115-120 ◽  
Author(s):  
Julian C. Schink ◽  
Larry J. Copeland
Keyword(s):  
Ovarian Cancer ◽  
Response Rate ◽  
Clinical Information ◽  
Recurrent Ovarian Cancer ◽  
Retrospective Data ◽  
Cooperative Group ◽  
Chemosensitivity Assay ◽  
The Past ◽  
Chemosensitivity Assays ◽  
Better Than

In this era of personalized medicine, patients with recurrent ovarian cancer deserve better than the 25% response rate that is associated with drugs selected based on clinical information alone. In the past decade, marked laboratory improvements have enabled chemosensitivity assay testing to yield a 0.70 correlation with response, and to accurately predict progression-free and overall survival. Compelling retrospective data supporting the use of this technology cannot be ignored while waiting for a cooperative group to test whether chemosensitivity assay should be used to direct salvage therapy.

scholarly journals Matrix Drug Screen Identifies Synergistic Drug Combinations to Augment SMAC Mimetic Activity in Ovarian Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3784
Author(s):  
Anne M. Noonan ◽  
Amanda Cousins ◽  
David Anderson ◽  
Kristen P. Zeligs ◽  
Kristen Bunch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Throughput Screening ◽  
Therapeutic Potential ◽  
Single Agent ◽  
Recurrent Ovarian Cancer ◽  
Drug Combinations ◽  
Smac Mimetic ◽  
Synergistic Drug Combinations

Inhibitor of apoptosis (IAP) proteins are frequently upregulated in ovarian cancer, resulting in the evasion of apoptosis and enhanced cellular survival. Birinapant, a synthetic second mitochondrial activator of caspases (SMAC) mimetic, suppresses the functions of IAP proteins in order to enhance apoptotic pathways and facilitate tumor death. Despite on-target activity, however, pre-clinical trials of single-agent birinapant have exhibited minimal activity in the recurrent ovarian cancer setting. To augment the therapeutic potential of birinapant, we utilized a high-throughput screening matrix to identify synergistic drug combinations. Of those combinations identified, birinapant plus docetaxel was selected for further evaluation, given its remarkable synergy both in vitro and in vivo. We showed that this synergy results from multiple convergent pathways to include increased caspase activation, docetaxel-mediated TNF-α upregulation, alternative NF-kB signaling, and birinapant-induced microtubule stabilization. These findings provide a rationale for the integration of birinapant and docetaxel in a phase 2 clinical trial for recurrent ovarian cancer where treatment options are often limited and minimally effective.

In vitro chemosensitivity assay for patients with gynecologic sarcoma.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. e20513-e20513
Author(s):  
A. Santin ◽  
J. Varughese ◽  
J. Lea
Keyword(s):  
Chemosensitivity Assay ◽  
In Vitro Chemosensitivity

A novel autologous oxidized whole-tumor antigen vaccine therapy for recurrent ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5023-5023
Author(s):  
Lana Kandalaft
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Dendritic Cell ◽  
Tumor Antigen ◽  
Ovarian Tumor ◽  
Recurrent Ovarian Cancer ◽  
Normal Donor ◽  
Tumor Lysate ◽  
Cell Responses

5023 Background: Despite surgical and chemotherapeutic advances, the death rate from ovarian cancer has not changed. We report here an enhanced dendritic cell vaccine platform developed for clinical testing. Furthermore we report the application of this novel platform comprising of dendritic cell (DC)-based autologous whole tumor antigen vaccination in a pilot study of patients with recurrent ovarian cancer. Methods: To determine the optimal tumor lysate preparation for loading DCs, ovarian tumor lines were prepared by HOCl-oxidation, UVB-irradiation or freeze and thaw. Normal donor DCs were evaluated for tumor lysate uptake, cytokine and chemokine productions and phenotype. The optimal lysate preparation, was used in a phase I study where five patients with recurrent ovarian cancer with available tumor lysate from secondary debulking surgery underwent intranodal vaccination with OC-DC, an autologous DC preparation pulsed with HOCL oxidized autologous tumor cells. Feasibility, safety, and biological and clinical efficacy were evaluated. Results: Normal donor DCs pulsed with HOCl-oxidized tumor lines demonstrated the highest tumor lysate uptake, matured efficiently after LPS and IFN-gamma stimulation, and produced higher levels of proinflammatory cytokines and chemokines. In vitro, these lysates loaded DCs primed T cell responses against ovarian tumor associated antigens and effectively expanded against tumor specific T cells from donors and patients. Therapy was feasible and well tolerated in all subjects. Vaccination with OC-DC produced limited grade 1 toxicities and elicited tumor-specific T cell responses. Moreover specific HLA-A2-restricted responses were documented following vaccination and HER-2/neu specific T cells were expanded following 10 days of in vitro culture. Patients exhibiting immune response demonstrated clinical benefit including two patients who demonstrated remission inversion on vaccine maintenance. Conclusions: We developed a DC-HOCl oxidized whole tumor lysate vaccine which was safe and well-tolerated by patients. The vaccine was highly proinflammatory and elicited cellular and humoral anti-tumor responses establishing a platform for immune-combinatorial therapy.

Clinical Trials in Recurrent Ovarian Cancer

2011 ◽  
Vol 21 (4) ◽  
pp. 771-775 ◽  
Author(s):  
Michael Friedlander ◽  
Edward Trimble ◽  
Anna Tinker ◽  
David Alberts ◽  
Elisabeth Avall-Lundqvist ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Gynecologic Cancer ◽  
Recurrent Ovarian Cancer ◽  
Consensus Conference ◽  
Ca 125 ◽  
Therapeutic Approaches ◽  
Cooperative Research ◽  
International Consensus

The 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup was held in Vancouver, Canada, in June 2010. Representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. Group C, 1 of the 3 discussion groups, examined recurrent ovarian cancer, and we report the consensus reached regarding 4 questions. These included the following: (1) What is the role of cytoreductive surgery for recurrent ovarian cancer? (2) How do we define distinct patient populations in need of specific therapeutic approaches? (3) Should end points for trials with recurrent disease vary from those of first-line trials? (4) Is CA-125 progression alone sufficient for entry/eligibility into clinical trials?

scholarly journals The Impact of Pegylated Liposomal Doxorubicin in Recurrent Ovarian Cancer : An Updated Meta-Analysis of Randomized Clinical Trials

2021 ◽  
Author(s):  
Xin-Ru Li ◽  
Yi Zhu ◽  
Guo-Nan Zhang ◽  
Jian-Ming Huang ◽  
Li-Xia Pei
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Side Effects ◽  
Confidence Level ◽  
Liposomal Doxorubicin ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Pegylated Liposomal Doxorubicin ◽  
Recurrent Ovarian Cancer ◽  
Cochrane Library

Abstract Background: Pegylated Liposomal Doxorubicin (PLD) could improve the survival rate of patients with recurrent ovarian cancer in previous meta-analysis studies. The aim of the present meta-analysis was to further update the role of PLD in the treatment of recurrent ovarian cancer.Methods: Literature search was performed by using the electronic databases Medicine, EMBASE, Web of Science, and Cochrane library until 27 July 2020. We only restricted the randomized clinical trials. Study specific hazard ratios and 95% confidence level (HR/95% CI), risk ratios and 95% confidence level (RR/95% CI), were pooled using a random effect model. Results: 10 studies (12 trials) were included after screening of 940 articles. We categorized the eligible studies into two groups: the doublet regimens (four trials, 1767 patients) resulted that PLD plus carboplatin(carbo) provided superior progression free survival (PFS) (HR, 0.85; 95% CI, 0.74-0.97) and similar overall survival (OS) (HR, 1.00; 95% CI, 0.88-1.14) compared PAC plus carbo. PLD plus carboplatin was associated with significantly more anemia and Thrombocytopenia, other side effects well-tolerated. In platin resistant patients, the monotherapy regimens (eight trials, 1980 patients) resulted that PLD had similar PFS (HR, 1.02; 95% CI, 0.90–1.16) and OS (HR, 0.88; 95% CI, 0.77–1.01) to other monotherapies. PLD alone was more associated with mucositis/stomatitis and hand-foot syndrome, other side effects well-tolerated.Conclusion: In platinum-sensitive recurrent ovarian cancer, PLD plus carbo is more effective than PAC plus carbo. In platinum-resistant or refractory recurrent ovarian cancer, PLD has similar survival to others monotherapies. For side effects, PLD plus carbo or monotherapy chemotherapy both were well-tolerated.

scholarly journals Stenoparib, an Inhibitor of Cellular Poly(ADP-Ribose) Polymerase, Blocks Replication of the SARS-CoV-2 and HCoV-NL63 Human Coronaviruses In Vitro

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nathan E. Stone ◽  
Sierra A. Jaramillo ◽  
Ashley N. Jones ◽  
Adam J. Vazquez ◽  
Madison Martz ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Viral Replication ◽  
Phase Ii ◽  
Parp Inhibitor ◽  
Target Range ◽  
Phase Ii Clinical Trials ◽  
Human Coronaviruses ◽  
Respiratory Coronavirus

ABSTRACT By late 2020, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had caused tens of millions of infections and over 1 million deaths worldwide. A protective vaccine and more effective therapeutics are urgently needed. We evaluated a new poly(ADP-ribose) polymerase (PARP) inhibitor, stenoparib, that recently advanced to phase II clinical trials for treatment of ovarian cancer, for activity against human respiratory coronaviruses, including SARS-CoV-2, in vitro. Stenoparib exhibits dose-dependent suppression of SARS-CoV-2 multiplication and spread in Vero E6 monkey kidney and Calu-3 human lung adenocarcinoma cells. Stenoparib was also strongly inhibitory to the human seasonal respiratory coronavirus HCoV-NL63. Compared to remdesivir, which inhibits viral replication downstream of cell entry, stenoparib impedes entry and postentry processes, as determined by time-of-addition (TOA) experiments. Moreover, a 10 μM dosage of stenoparib—below the approximated 25.5 μM half-maximally effective concentration (EC50)—combined with 0.5 μM remdesivir suppressed coronavirus growth by more than 90%, indicating a potentially synergistic effect for this drug combination. Stenoparib as a stand-alone or as part of combinatorial therapy with remdesivir should be a valuable addition to the arsenal against COVID-19. IMPORTANCE New therapeutics are urgently needed in the fight against COVID-19. Repurposing drugs that are either already approved for human use or are in advanced stages of the approval process can facilitate more rapid advances toward this goal. The PARP inhibitor stenoparib may be such a drug, as it is currently in phase II clinical trials for the treatment of ovarian cancer and its safety and dosage in humans have already been established. Our results indicate that stenoparib possesses strong antiviral activity against SARS-CoV-2 and other coronaviruses in vitro. This activity appears to be based on multiple modes of action, where both pre-entry and postentry viral replication processes are impeded. This may provide a therapeutic advantage over many current options that have a narrower target range. Moreover, our results suggest that stenoparib and remdesivir in combination may be especially potent against coronavirus infection.

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