Tag Archives: oxaliplatin

Access Pharma Commences European Phase II Study of ProLindac™ + Paclitaxel In Platinum-Sensitive Ovarian Cancer Patients

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Access Pharmaceuticals announces commencement of a Phase 2 combination trial for its second generation DACH-platinum cancer drug, ProLindac™ (formerly known as AP5346), in platinum-sensitive ovarian cancer patients. This trial is an open-label, Phase 2 study of ProLindac™ given intravenously with paclitaxel. The combination trial will be conducted in up to eight European participating centers.

Access Pharmaceuticals, Inc., a biopharmaceutical company leveraging its proprietary drug-delivery platforms to develop treatments in the areas of oncology, cancer supportive care and diabetes, announces commencement of a Phase 2 combination trial for its second generation DACH-platinum [the active part of the currently-marketed drug, oxaliplatin] cancer drug, ProLindac™ (formerly known as AP5346), in platinum-sensitive ovarian cancer patients. This trial is an open-label, Phase 2 study of ProLindac™ given intravenously with paclitaxel. The combination trial will be conducted in up to eight European participating centers.

“We are very pleased to be able to begin this trial, which will be the first of several ProLindac-based combination studies in a variety of indications,” said Prof. Esteban Cvitkovic, Vice Chairman Europe and Senior Director Clinical Oncology R&D, Access Pharmaceuticals, Inc. He continued, “The ambitious two-step design of the study will allow us to rapidly benchmark ProLindac/paclitaxel in a clinical setting where there is a clear need to establish an improved standard for long-term tumor responses. When treated using the current first-line combination of carboplatin/paclitaxel, more than half of patients with advanced ovarian cancer will relapse. There are very few second-line options. Approved agents for second-line and later therapy are currently focused primarily on the palliation of more resistant tumors. This lack of valid second-line options presents an opportunity to prove the role of ProLindac-based combinations in ovarian cancer.”

“After optimizing ProLindac’s scaled-up manufacturing process, we are pleased to be moving forward with its clinical development,” said Jeff Davis, President and CEO, Access Pharmaceuticals, Inc. He continued, “We think there is a significant clinical need and commercial opportunity for safer, more effective platinum drugs.”

Access Pharmaceuticals previously announced positive safety and efficacy results from its Phase 2 monotherapy clinical study of ProLindac™ in late-stage, heavily pretreated ovarian cancer patients. In this study, 66% of patients who received the highest dose achieved clinically meaningful disease stabilization according to RECIST [Response Evaluation Criteria in Solid Tumors] criteria, including sustained significant reductions in CA-125 (the established specific serum marker for ovarian cancer) observed in several patients. No patient in any dose group exhibited signs of acute neurotoxicity, which is a major adverse side-effect of the approved DACH platinum, Eloxatin®. ProLindac was very well tolerated, with only minor sporadic hematologic toxicity.

Access Pharmaceuticals is evaluating various indications where DACH platinum-based combinations have been proven active, such as hepatocarcinoma, biliary tree cancer and pancreatic cancer before deciding on an expanded Phase 2 program.

About ProLindac:

ProLindac™ is a novel DACH platinum prodrug that has completed a phase 2 monotherapy study in ovarian cancer patients. It is a polymer therapeutic that utilizes a safe, water-soluble nanoparticulate system to deliver DACH platinum to tumors, while reducing delivery to normal tissue, resulting in an increase in drug effectiveness and a significant decrease in toxic side-effects seen in the currently marketed DACH platinum, Eloxatin®.

For more information, please visit http://www.accesspharma.com/product-programs/prolindac/.

Source: Access Pharmaceuticals Commences ProLindac Phase 2 Combination Clinical Trial – Multicenter, Open-Label Trial to Target Platinum-Sensitive Ovarian-Cancer Patients, News Release, Access Pharmaceuticals, Inc., November 3, 2010.

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Researchers Identify “Missing Link” Underlying DNA Repair & Platinum Drug Resistance

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Researchers have discovered an enzyme crucial to a type of DNA repair that also causes resistance to a class of cancer drugs most commonly used against ovarian cancer.

Scientists from The University of Texas MD Anderson Cancer Center and the Life Sciences Institute of Zhejiang University in China report the discovery of the enzyme and its role in repairing DNA damage called “cross-linking” in the Science Express advance online publication of Science.

Junjie Chen, Ph.D., Professor and Chair, Department of Experimental Radiation Oncology, University of Texas M.D. Anderson Cancer Center

“This pathway that repairs cross-linking damage is a common factor in a variety of cancers, including breast cancer and especially in ovarian cancer. If the pathway is active, it undoes the therapeutic effect of cisplatin and similar therapies,” said co-corresponding author Junjie Chen, Ph.D., professor and chair of MD Anderson’s Department of Experimental Radiation Oncology.

The platinum-based chemotherapies such as cisplatin, carboplatin and oxaliplatin work by causing DNA cross-linking in cancer cells, which blocks their ability to divide and leads to cell death. Cross-linking occurs when one of the two strands of DNA in a cell branches out and links to the other strand.

Cisplatin and similar drugs are often initially effective against ovarian cancer, Chen said, but over time the disease becomes resistant and progresses.

Scientists have known that the protein complex known as FANCI–FANCD2 responds to DNA damage and repairs cross-linking, but the details of how the complex works have been unknown. “The breakthrough in this research is that we finally found an enzyme involved in the repair process,” Chen said.

The enzyme, which they named FAN1, appears to be a nuclease, which is capable of slicing through strands of DNA.

In a series of experiments, Chen and colleagues demonstrated how the protein complex summons FAN1, connects with the enzyme and moves it to the site of DNA cross-linking. They also showed that FAN1 cleaves branched DNA but leaves the normal, separate double-stranded DNA alone. Mutant versions of FAN1 were unable to slice branched DNA.

Like a lock and key

The researchers also demonstrated that FAN1 cannot get at DNA damage without being taken there by the FANCI-FANCD2 protein complex, which detects and moves to the damaged site. The complex recruits the FAN1 enzyme by acquiring a single ubiquitin molecule. FAN1 connects with the complex by binding to the ubiquitin site.

“It’s like a lock and key system, once they fit, FAN1 is recruited,” Chen said.

Analyzing the activity of this repair pathway could guide treatment for cancer patients, Chen said, with the platinum-based therapies used when the cross-linking repair mechanism is less active.

Scientists had shown previously that DNA repair was much less efficient when FANCI and FANCD2 lack the single ubiquitin. DNA response and damage-repair proteins can be recruited to damage sites by the proteins’ ubiquitin-binding domains. The team first identified a protein that had both a ubiquitin-binding domain and a known nuclease domain. When they treated cells with mitomycin C, which promotes DNA cross-linking, that protein, then known as KIAA1018, gathered at damage sites. This led them to the functional experiments that established its role in DNA repair.

They renamed the protein FAN1, short for Fanconi anemia-associated nuclease 1. The FANCI-FANCD2 complex is ubiquitinated by an Fanconi anemia (FA) core complex containing eight FA proteins. These genes and proteins were discovered during research of FA, a rare disease caused by mutations in 13 fanc genes that is characterized by congenital malformations, bone marrow failure, cancer and hypersensitivity to DNA cross-linking agents.

Chen said the FANCI-FANCD2 pathway also is associated with the BRCA1 and BRCA2 pathways, which are involved in homologous recombination repair. Scientists know that homologous recombination repair is also required for the repair of DNA cross-links, but the exact details remain to be resolved, Chen said. Mutations to BRCA1 and BRCA2 are known to raise a woman’s risk for ovarian and breast cancers and are found in about 5-10 percent of women with either disease.

Co-authors with Chen are co-first author Gargi Ghosal, Ph.D., and Jingsong Yuan, Ph.D., also of Experimental Radiation Oncology at MD Anderson; and co-corresponding author Jun Huang, Ph.D., co-first author Ting Liu, Ph.D., of the Life Sciences Institute of Zhejiang University in Hangzhou, China.

This research was funded by a grant from the U.S. National Institutes of Health and the Startup Fund at Zhejiang University.

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2009 ASCO Annual Meeting Highlights: Ovarian Cancer & Select General Issues

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The 2009 American Society of Clinical Oncology (ASCO) Annual Meeting was held in Orlando, Florida from May 29 through June 2, 2009.  We provide below select highlights from the 2009 ASCO Annual Meeting that relate to ovarian cancer and other general issues.

The 2009 American Society of Clinical Oncology (ASCO) Annual Meeting was held in Orlando, Florida from May 29 through June 2, 2009.  We provide below select highlights from the 2009 ASCO Annual Meeting that relate to ovarian cancer and other general issues. Learn more about How to Read a Medical Abstract in a Research Study.

Development Time of Cancer Clinical Trials Linked to Accrual Goals.

Physicians Need to Address Prescription Costs With Patients Who Participate In Clinical Trials.

Availability of Experimental Therapy Outside of Randomized Clinical Trials In Oncology.

ASCO Fertility Preservation Guidelines For Cancer Patients Not Widely Followed By Oncologists.

Ginger (Zindol®) Quells Cancer Patients’ Chemotherapy-Related Nausea.

Early Treatment of Recurrent Ovarian Cancer Based Upon Rising CA-125 Levels Does Not Increase Survival.

Body Mass Index (BMI) Should Be Taken Into Account When Assessing A Cancer Patient’s Vitamin D Status.

Extreme Drug Resistance (EDR) Assay Results Do Not Independently Predict Or Alter The Outcomes of Patients With Epithelial Ovarian Cancer Who Are Treated With Optimal Cytoreductive Surgery Followed By Platinum & Taxane Combination Chemotherapy in Either a Primary or Recurrent Setting.

Systematic Review Of Past Study Results For Use of Cytoreductive Surgery Combined With Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

Preliminary Results From Phase II Study of Oxaliplatin+Docetaxel+Bevacizumab As First Line Treatment of Advanced Ovarian Cancer Show 62% Overall Response Rate & 70% One-Year Progression Free Survival.

Combined Weekly Docetaxel + Gemcitabine In Relapsed Ovarian Cancer & Peritoneal Cancer Produces 59% Overall Response Rate.

A Phase II Trial of Irinotecan & Oral Etoposide Chemotherapy in Recurrent Ovarian Cancer Patients Produces 47% Overall Response Rate & 81% Clinical Benefit Rate.

Weekly Bevacizumab & Pegylated Liposomal Doxorubicin Produce 55% Clinical Benefit Rate In Progressing/Recurrent Ovarian Cancer Patients.

Phase II Study of Belotecan (CKD-602)+ Carboplatin Demonstrates 53% Overall Response Rate in Recurrent Ovarian Cancer Patients.

Single Agent Voreloxin Produces 11% Overall Response Rate & 52% Disease Control Rate in Phase II Study Involving Women with Platinum-Resistant Ovarian Cancer.

A Phase II Study of Patupilone In Patients With Platinum Refractory/Resistant Ovarian, Primary Fallopian, or Peritoneal Cancer Produces 48% Clinical Benefit Rate.

Trabectedin (Yondelis®) + Pegylated Liposomal Doxorubicin (PLD) Produces Better Response Than PLD Alone.

M.D. Anderson Cancer Center Finds Anti-VEGF Therapy Is Highly Effective In Patients With Ovarian Granulosa Cell Tumors.

M.D. Anderson Cancer Center Finds That Increased Angiogenesis Is A Significant Predictor Of Poor Clinical Outcome In Patients With Sex-Cord Stromal Tumors; Suggests Anti-Angiogenesis Therapy is Warranted For This Subtype of Ovarian Cancer.

ZYBRESTAT™ (Combretastatin A-4 phosphate) Produces 32% Confirmed Partial Response Rate (RR) in Evaluable Patients With Platinum Resistant Ovarian Cancer (25% RR if total enrolled patients used as denominator).

ASSIST-5 Trial of TELCYTA® + Pegylated Liposomal Doxorubicin Produces 12% Response Rate (With One Complete Response) in Patients With Platinum Refractory and Resistant Ovarian Cancer.

Two Studies Provide Contradictory Data for Use of Carboplatin + Pegylated Liposomal Doxorubicin in Ovarian Cancer

OGX-427 Treatment Demonstrates Safety, Evidence of Declines in Circulating Tumor Cells and Reductions in Tumor Markers in a Phase I Cancer Trial, Including 60% Response Rate (Based Upon Declining CA125) For Ovarian Cancer Patients.

Maintenance BIBF 1120 Could Delay Disease Progression in Recurrent Ovarian Cancer.

Oral PARP Inhibitor Olaparib (AZD2281) Effective Against BRCA-Deficient Advanced Ovarian Cancer.

Carfilzomib (PX-171-007) Produces Stable Disease For 4+ Months In One Ovarian Cancer Patient Who Failed Under Four Previous Treatment Lines – Phase II Solid Tumor Trial.

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About The American Society of Clinical Oncology

The American Society of Clinical Oncology is a non-profit organization founded in 1964 with the overarching goals of improving cancer care and prevention. More than 27,000 oncology practitioners belong to ASCO, representing all oncology disciplines and subspecialties. Members include physicians and health-care professionals in all levels of the practice of oncology. To view 2009 ASCO Annual Meeting presentation abstracts, click here.  To view 2009 ASCO Annual Meeting presentation abstracts regarding ovarian cancer, click here.  To view ASCO ovarian cancer information, click here.

About Cancer.Net

Cancer.Net, formerly People Living With Cancer (PLWC), brings the expertise and resources of the American Society of Clinical Oncology (ASCO), the voice of the world’s cancer physicians, to people living with cancer and those who care for and care about them. ASCO is composed of more than 27,000 oncologists globally who are the leaders in advancing cancer care. All the information and content on Cancer.Net was developed and approved by the cancer doctors who are members of ASCO, making Cancer.Net the most up-to-date and trusted resource for cancer information on the Internet. Cancer.Net is made possible by The ASCO Cancer Foundation, which provides support for cutting-edge cancer research, professional education, and patient information.

Cancer.Net provides timely, oncologist-approved information to help patients and families make informed health-care decisions. All content is subject to a formal peer-review process by the Cancer.Net Editorial Board, composed of more than 150 medical, surgical, radiation, and pediatric oncologists, oncology nurses, social workers, and patient advocates. In addition, ASCO editorial staff reviews the content for easy readability. Cancer.Net content is reviewed on an annual basis or as needed.

To view Cancer.Net ovarian cancer information, click here.

Learn more about How to Read a Medical Abstract in a Research Study, Cancer.Net.

2009 Society of Gynecologic Oncologists Annual Meeting Ovarian Cancer Highlights

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From February 5th through 8th, 2009, the Society of Gynecologic Oncologists’ (SGO) held its 40th Annual Meeting on Women’s Cancer in San Antonio, Texas. The meeting, viewed as the preeminent scientific and educational conference for women’s cancer care specialists, featured more than 350 scientific oral and poster presentations as well as educational sessions dealing with advances in the care and treatment of women’s cancers.

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From February 5th through 8th, 2009, the Society of Gynecologic Oncologists‘ (SGO)  held its 40th Annual Meeting on Women’s Cancer in San Antonio, Texas.  The meeting, viewed as the preeminent scientific and educational conference for women’s cancer care specialists, featured more than 350 scientific oral and poster presentations as well as educational sessions dealing with advances in the care and treatment of women’s cancers.  Several important presentations relating to ovarian cancer were made during the meeting and are highlighted below:

  • SGO: IVF Confers Slight Long-Term Risk of Ovarian Cancer, by Charles Bankhead, Medical News from SGO: Society of Gynecologic Oncologists Meeting, February 6, 2009 [Presentation Source:  Burger C, et al; The risk of borderline and invasive ovarian tumors after ovarian stimulation for in vitro fertilization in a large Dutch cohort after 15 years of follow-up, SGO 2009; 112(Suppl 1): Abstract 6].
  • SGO: Optimal Surgery Holds Benefits in Ovarian Cancer with Upper Abdominal Disease, by Charles Bankhead, Medical News from SGO: Society of Gynecologic Oncologists Meeting, February 6, 2009 [Presentation Source:  Zivanovic O, et al; Upper abdominal disease cephalad to the greater omentum and the impact on progression-free survival in patients with stage IIIC ovarian cancer;  SGO 2009; 112(Suppl 1): Abstract 1].
  • SGO: Rectovaginal Nodules Predict Bowel Perforation Risk with Bevacizumab, by Charles Bankhead, Medical News from SGO: Society of Gynecologic Oncologists Meeting, February 9, 2009 [Presentation Source:  Richardson DL, et al; Which factors predict bowel complications in patients with recurrent epithelial ovarian cancer being treated with bevacizumab? SGO 2009; 112(Suppl 1): Abstract 41].
  • Low Completion Rates for GOG 172 Intraperitoneal Chemotherapy Regimen: See Aletti G, et al Intraperitoneal chemotherapy for ovarian cancer: Exploring the “dark side” of the moon” SGO 2009; 112(Suppl 1): Abstract 40 (Source:  SGO: Few Ovarian Cancer Patients Tolerate Intraperitoneal Regimen, by Charles Bankhead, Medical News from SGO: Society of Gynecologic Oncologists Meeting, February 11, 2009).
  • Vermillion Presents Critical Data From Its OVA1 Clinical Trial, Vermillion Inc. News Release, February 10, 2009 [Presentation based upon a study entitled, A biomarker panel for distinguishing between malignant and benign ovarian tumors, which was co-authored by Fred Ueland, MD, Associate Professor of Gynecologic Oncology at the University of Kentucky and Principal Investigator of the OVA1 clinical trial, and Zhen Zhang, PhD, Associate Professor of Pathology at the Johns Hopkins University School of Medicine as well as Vermillion scientists].

About the Society of Gynecologic Oncologists

The SGO is a national medical specialty organization of physicians who are trained in the comprehensive management of women with malignancies of the reproductive tract. Its purpose is to improve the care of women with gynecologic cancer by encouraging research, disseminating knowledge which will raise the standards of practice in the prevention and treatment of gynecologic malignancies, and cooperating with other organizations interested in women’s health care, oncology and related fields. The Society’s membership, totaling more than 1280, is primarily comprised of gynecologic oncologists, as well as other related medical specialists including medical oncologists, radiation oncologists and pathologists. SGO members provide multidisciplinary cancer treatment including chemotherapy, radiation therapy, surgery and supportive care. More information on the SGO can be found at http://www.sgo.org.