If You Have Penicillin Allergies, You Should Get Retested

Patients who have been diagnosed with penicillin allergies probably aren?t allergic to it anymore, according to a new finding. The allergy wears off over time, but most people live the rest of their lives believing they’re still allergic, and pay for more expensive, unnecessary medication.

by Samantha Olson? Release Date: November 9, 2014

Mayo Clinic Allergist Dr. Thanai Pongdee, and his team retested 384 patients and found 94 percent of them were not allergic. The patients were scheduled to undergo several different types of surgeries when they were tested. Pongdee said he expected they would find maybe half of the patients still allergic to penicillin, a common medical allergy. However, when almost all of the patients found they weren?t allergic, it more than confirmed a suspicion doctors had for a long time.

Test Tube Penicillin
Test Tube Image Courtesy of Shutterstock via RePubHub

“We knew that the majority of people who list penicillin as an allergy actually aren?t allergic when they are reevaluated, so if you can determine they are not, you can avoid using more toxic and more expensive antibiotics,” Pongdee told NBC News. “It doesn?t happen very often that a health care provider challenges the presumption that the patient is still allergic. Many don?t realize that this is something a person may lose over time.”

When a patient walks into the hospital, one of the first questions they?re asked is, “Are you allergic to any medications?” Ten percent of the population report they’re allergic to penicillin, making it the most commonly reported drug allergy, according to the American College of Allergy, Asthma & Immunology?(ACAAI). A patient with an allergy may develop hives, swelling, throat tightening, wheezing, coughing, and difficulty breathing. In severe cases, it can cause a patient to go into sudden anaphylactic shock, which will rapidly worsen and could become deadly.

Penicillin has been around since 1928, and has been used to treat a variety of conditions, such as strep throat, ear infection, or sinus infection. Penicillin is the base of many front-line drugs, and if you can?t take one of those, you?re often forced to take a more expensive alternative with more side effects.

When one Long Island mother, whose son was diagnosed with a penicillin allergy at the age of 8, was asked if she would have him retested, she said, “I definitely would. It would stop us from worrying because he doesn’t wear a bracelet. He broke out in a rash and hives after he was given amocycillin for his strep throat.”

In most cases their sensitivity to penicillin will lessen overtime and can be treated safely with the drug. It?s exciting news for patients with documented penicillin allergies because they can start receiving cheaper drugs, such as the generic penicillin-based amoxicillin used to fight bacterial infections. Most people are diagnosed when they are toddlers due to an adverse reaction, but then live the rest of their lives avoiding a drug allergy with unfounded fears.

?There are two issues: these patients are put on other antibiotics which [are] less effective and potentially have more side-effects,? Family Allergist Dr. James Sublett, the incoming president of the ACAAI told NBC News. ?The other is cost. A very commonly used substitute, for example Levaquin, is seven to eight times more expensive for a 10-day course than a similar course of generic Augmentin, a penicillin drug.?

(Reprinted with license and permission from Medical Daily)RePubHub Banner

 

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OncoTherapy Network Highlights National Breast Cancer Awareness Month

Breast Cancer RibbonEvery October, National Breast Cancer Awareness Month [3] is observed to help spread the word about early detection. While screening is an integral part of breast cancer prevention, treatment options for thousands of patients diagnosed each year with breast cancer continues to be a focal point in oncology.

UBM Medica US announced that OncoTherapyNetwork [1], a leading online community to help oncologists and other clinicians gain a better understanding of the newest information available regarding the use of targeted therapies and immunotherapies, discusses some of the latest research on breast cancer treatment [2].

The featured articles below discuss some of the most recent research findings, including potential treatment options for both HER2-positive and triple-negative breast cancers:

? Neoadjuvant Carboplatin Boosts Targeted Therapy Responses in Triple-Negative Breast Cancer
The addition of neoadjuvant carboplatin to a regimen of taxane-anthracycline chemotherapy and targeted therapy substantially increased pathological complete responses in patients with stage II/III triple-negative breast cancer [4] (but not in patients with HER2-positive disease).

? Breast Cancer Vaccine Showing Promise in Women With HER2 Overexpression
Recent findings from a phase II randomized clinical trial demonstrates that a breast cancer vaccine known as GP2, may help at preventing disease recurrence in women with HER2 protein overexpression [5].

? Knockdown of CD24 May Enhance Efficacy of Targeted Agents in HER2-Positive Breast Cancer
Therapeutic targeting of CD24 may enhance the efficacy of targeted agents, such as trastuzumab and lapatinib, in treatment of human epidermal growth factor receptor 2 (HER2)-positive breast Cancer [6].

References:
1. www.oncotherapynetwork.com/?cid=pr10152014
2. www.oncotherapynetwork.com/breast-cancer-targets?cid=pr10152014

3. healthfinder.gov/nho/octobertoolkit.aspx
4. www.oncotherapynetwork.com/breast-cancer-targets/neoadjuvant-carboplatin-booststargeted-
therapy-responses-triple-negative-breast-cancer?cid=pr10152014
5. www.oncotherapynetwork.com/breast-cancer-targets/breast-cancer-vaccine-showingpromise-
women-her2-overexpression?cid=pr10152014
6. www.oncotherapynetwork.com/breast-cancer-targets/knockdown-cd24-may-enhanceefficacy-
targeted-agents-her2-positive-breast-cancer?cid=pr10152014
About UBM Medica US
Addressing today’s healthcare information needs, UBM Medica US, delivers strategic, integrated communications solutions and comprehensive reach — online, in print, via custom programs and live events. Improving the effectiveness of healthcare through information and education, UBM Medica US provides unbiased clinical, practical, and business information for physicians, providers and payers resulting in improved quality of care for patients around the world. Through journals, magazines, online communities, live and digital events, and other valuable resources, UBM Medica US also delivers comprehensive communication solutions for the pharmaceutical and related industries. Online communities include CancerNetwork.com, ConsultantLive.com, DiagnosticImaging.com, RheumatologyNetwork.com, OBGYN.net, PhysiciansPractice.com, PsychiatricTimes.com and SearchMedica.com. UBM Medica US is part of UBM Americas which, through a range of aligned interactive environments, both physical and digital ? increases business effectiveness for both customers and audiences through meaningful experiences, knowledge and connections.?For more information, visit www.UBMMedicaUS.com.

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(Reprinted with license and permission from PR Newswire.)

New Oncology Consortia Expand Translational Science Research Offerings

Criterium proudly announces our two newest Oncology Consortia Groups: ATOMIC (The Academic Thoracic Oncology Medical Investigator’s Consortium) focusing on Thoracic and Lung Cancers, and ABRCC (The Academic Breast Cancer Consortium), dedicated to Breast Cancer research. These new consortia consist of a collaboration of outstanding Cancer Research Consortia that deliver innovative research and unparalleled expertise. These two new consortia will join Criterium’s already successful AGICC (the Academic GI Cancer Consortium) directed by Dr. Wells Messersmith, established in 2008, and AMyC (the Academic Myeloma Consortium) established in 2010 with Dr. Brian G. M. Durie directing 3 high profile studies.

ALL Consortia Logos

All of Criterium’s Oncology Consortia specialize in translational research design to bring novel cancer therapies to market in accelerated time frames. “These new types of therapies allow cancer drugs to more effectively target only the destructive cancer cells, while allowing healthy cells to remain untouched, thereby providing a less toxic treatment, with better patient survival outcomes,” stated Dr. Jack Macdonald, the Senior Medical Consultant for the Oncology Consortia.

Dr. D. Ross Camidge MD PHD ATOMIC

Dr. D. Ross Camidge of the University of Colorado?s Cancer Center in Aurora, Colorado has been appointed as ATOMIC’s Director. “ATOMIC brings together a powerful mixture of mature thought leaders and the next generation of experts with the sole goal of designing and completing clinical trials that will change the way we do business in thoracic oncology for the better,” says Camidge.

Also from the University of Colorado is Dr. Peter Kabos, Dr Peter Kabos MD ABRCCthe newly named Director for ABRCC. “ABRCC is an academic consortium formed for the new era of clinical trial design and implementation. Our goal is to rapidly translate advances in breast cancer research into targeted therapies that will benefit our patients,” states Kabos. Both bring an exceptional set of credentials in advanced research and organizational skills to the collaboration.

The Consortia Model for research and development in pharmaceuticals utilizes translational science methodologies to streamline cancer research. The Consortia rosters are presently represented by Key Opinion Leaders (KOLs) and Top Investigators at 24 of the most prestigious institutions in the USA. In this way, Criterium brings together these physician-scientists into highly effective and productive new drug development entities. To learn more, please visit: www.CriteriumInc.com/OCC.php

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Cancer Leaves a Common Fingerprint on DNA

Chemical alterations to genes appear key to tumor development
by Shawna Williams, Johns Hopkins Medicine – Release Date: August 26, 2014
(Displayed with permission from redOrbit.com – 2014 redOrbit)

Fast Facts:

  • Alterations to chemicals attached to DNA, known as epigenetic changes, affect how genes do their work and have been linked to colon cancer.
  • A new study of six different cancer types found distinctive epigenetic changes in all of them.
  • Conclusion: Epigenetic changes are key to cancer development.
DNA Image Courtesy of Thinkstock via RePubHub
DNA Image Courtesy of Thinkstock via RePubHub

Regardless of their stage or type, cancers appear to share a telltale signature of widespread changes to the so-called epigenome, according to a team of researchers. In a study of a broad variety of cancers, published online in Genome Medicine on Aug. 26, the investigators say they have found widespread and distinctive changes to chemical marks known as methyl groups attached to DNA. Those marks help govern whether genes are turned “on” or “off”, and ultimately how the cell behaves. Such reversible chemical marks on DNA are known as epigenetic, and together they make up the epigenome.

“Regardless of the type of solid tumor, the pattern of methylation is much different on the genomes of cancerous cells than in healthy cells,” says Andrew Feinberg, M.D., M.P.H., a professor of medicine, molecular biology and genetics, oncology, and biostatistics at the Johns Hopkins University School of Medicine. Feinberg led the new study along with Rafael Irizarry, Ph.D., a professor of biostatics at Harvard University and the Dana-Farber Cancer Institute. “These changes happen very early in tumor formation, and we think they enable tumor cells to adapt to changes in their environment and thrive by quickly turning their genes on or off,” Feinberg says.

Feinberg, along with Johns Hopkins University School of Medicine oncology professor Bert Vogelstein, M.D., first identified abnormal methylation in some cancers in 1983. Since then, Feinberg?s and other research groups have found other cancer-associated changes in epigenetic marks. But only recently, says Feinberg, did researchers gain the tools needed to find out just how widespread these changes are.

For their study, the research team took DNA samples from breast, colon, lung, thyroid and pancreas tumors, and from healthy tissue, and analyzed methylation patterns on the DNA. “All of the tumors had big blocks of DNA where the methylation was randomized in cancer, leading to loss of methylation over big chunks and gain of methylation in smaller regions,” says Winston Timp, Ph.D., an assistant professor of biomedical engineering at Johns Hopkins. “The changes arise early in cancer development, suggesting that they could conspire with genetic mutations to aid cancer development,” he says.

The overall effect, Feinberg says, appears to be that cancers can easily turn genes “on” or “off” as needed. For example, they often switch off genes that cause dangerous cells to self-destruct while switching on genes that are normally only used very early in development and that enable cancers to spread and invade healthy tissue. “They have a toolbox that their healthy neighbors lack, and that gives them a competitive advantage,” Feinberg says.

“These insights into the cancer epigenome could provide a foundation for development of early screening or preventive treatment for cancer,” Timp says, suggesting that the distinctive methylation “fingerprint” could potentially be used to tell early-stage cancers apart from other, harmless growths. Even better, he says, would be to find a way to prevent the transition to a cancerous fingerprint from happening at all.

Other authors on the paper are Hector Corrada Bravo of the University of Maryland, College Park, and Oliver G. McDonald, Michael Goggins, Chris Umbricht and Martha Zeiger, all of The Johns Hopkins University.

The study was funded by the National Human Genome Research Institute (grant number HG003223), the National Cancer Institute (grant number CA054358), the National Institute of General Medical Sciences (grant numbers GM083084 and GM103552) and the National Center for Research Resources (grant number RR021967).

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Advantages and Challenges of Conducting Clinical Research in South Africa

Get To Know The South African Healthcare System

The South African healthcare system consists of public healthcare, which is financed and managed by the South African government, and private healthcare, which is primarily funded by health insurance and private direct fee for service payments. Private healthcare consumes more than 50% of total healthcare spending in South Africa, but only services about 20% of the population able to afford health insurance or direct funding of their healthcare needs.

South Africa Flag RoundThe Attraction of South Africa as Clinical Research Destination

South Africa is classified internationally as a developing country and is often viewed by the less-informed as a poorly developed African country. This is far from the truth.? South Africa has a long history of conducting clinical research; this translates to interest of the medical profession in furthering their knowledge and remaining at the cutting edge of medical development. This is a good indication of the pool of experienced clinical research staff available for research, which is growing and developing as the research environment changes over the years. Clinical research experience is of paramount importance in the South African research environment: it is a regulatory requirement that investigators may only participate as principal investigator after having participated in at least two different clinical trials as a sub-investigator.

A Sophisticated Infrastructure and Clinical Trial Support System

South Africa has a sophisticated infrastructure and clinical trial support system available. Laboratory support to process and analyze blood and tissue samples is readily available in all the large metropolitan cities in South Africa. Most, if not all, of the major laboratories have a clinical trial division that specifically caters for the clinical trial environment, and usually have some partnership/working relationship with the large multinational analytical laboratories. All FREEPIK Medical Imagesthe clinical laboratories are audited and accredited by SANAS. These facilities meet all of the international standard requirements.

Product Depots with Strict Control Mechanisms in Place

As South Africa is located quite a distance from the major manufacturing facilities in the USA, Europe and Asia, investigational product depots are often used to import and distribute clinical trial products to site. These facilities adhere to all international packaging and manufacturing (GMP) and clinical trial requirements (GCP). As they generally receive, store, and distribute clinical trial investigational product for a number of different studies and companies, they have very strict control mechanisms in place to ensure confidentiality and safety of clinical trial product. They are able to manage all types of investigational product at all temperature ranges.

Interested in more in-depth information on this topic? Download our complete article from the May 2014 Journal for Clinical Studies:

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The New Treatment Paradigm in Cancer Research

Dr J S Macdonald MDDr. John S. Macdonald
Senior Consultant for The Oncology Consortia of CRITERIUM, INC.

In the past, typical anti-cancer systemic therapies that worked, albeit poorly, did so by killing cancer cells only slightly better than they killed normal cells. There were relatively few of these drugs and they were given to patients with all kinds of cancers. This toxic therapy could be depended upon to make patients sick all the time while rarely making cancers significantly improve.? To effectively develop these new treatments, clinical investigators must not only be excellent physicians but also be first rate molecular and cellular biologists.

CHEMOTHERAPEUTIC AGENTS KILL MORE CELLS THAN THEY SHOULD
The classic chemotherapeutic agents are relatively non specific toxins that function by killing or at least seriously injuring cells. These agents cause significant toxicity to patients because all or most of the cells in the body are injured by these drugs. A successful chemotherapeutic agent kills cancer cells a little better than it kills normal cells.

CHEMOTHERAPY MAKING A CANCER COMPLETELY DISAPPEAR IS RARE
One of the real negative aspects of chemotherapy is that all patients receiving a drug experience toxicity which may be life threatening, but only a minority of patients with cancer will actually have treatment make the tumor regress. Having chemotherapy make a cancer completely disappear with treatment with the therapy producing a CR or complete response, is rare. The final phase III trials required to show that a new treatment is equal to or superior to a standard therapy, require hundreds of patients most of whom will be made sick by the therapy but not get any anti-tumor benefit.

CLASSIC CHEMOTHERAPY PRODUCES UNWANTED ADDITIONAL EFFECTS
Finally since classic chemotherapy agents are toxins they may produce late effects such as second cancers and major organ (bone marrow, kidney, liver, lung, etc.) damage in patients who receive treatment and or cured of their original cancers. So the bottom line with classic chemo is that these are agents that are always toxic, rarely curative, require hundreds of patients on clinical trials to demonstrate efficacy and may result in serious late effects.

Recently this paradigm of toxic relatively ineffective cancer therapies is changing. Because of increased knowledge of molecular biology and molecular genetics, more specific targeted therapies that are less toxic to normal cells are being developed. Some dramatic improvements in survival have been reported with such treatments.

IN TARGETED THERAPIES, ONLY CANCER CELLS ARE DAMAGED
AND NORMAL CELLS ARE SPARED

The key factors that make targeted cancer therapies and immunotherapy different from and in theory superior to chemotherapy are that these treatments dependent upon specific anti-tumor effects. In other words in the ideal situation only? the cancer cells are injured or killed with a targeted approach or an immunotherapy approach. Thus if a target exists only in tumor cells or is over expressed in tumor cells, then a targeted therapy only affects the cancer cell and does minimal if any damage to normal cells. Ideally the result is tumor death and no normal cell toxicity. Likewise with immunotherapy, the only cells damaged would be the cells (tumor cells) carrying the antigen or marker that the immune system recognizes. Again the result is that cancer cells are damaged and normal cells are spared.

TARGETED THERAPIES ARE MORE EFFICIENT AND LESS TOXIC
The factor to keep in mind is that the clinical development of more targeted therapies should clearly be much more efficient than development of chemotherapy. Only patients with the specific target are entered in clinical trials so the likelihood of benefit is increased. Targeted or immunotherapeutic treatments may be active against the tumor at dose levels that are minimally toxic. Thus small targeted relatively non toxic trials may be used in development of newer approaches to cancer treatment.

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Multiple Myeloma Compound Gets Orphan Drug Status

Dr J S Macdonald MDDr. John S. Macdonald
Senior Consultant for The Academic GI Cancer Consultant Consortium (AGICC) & The Academic Myeloma Consortium (AMyC) of The Oncology Consortia of CRITERIUM, INC.

The US Food and Drug Administration has granted orphan drug status to an experimental compound for multiple myeloma known as KRN5500.

This is the second orphan drug designation for KRN5500, which is a novel, intravenous, nonopioid, nonnarcotic compound in phase 2 clinical development by DARA BioSciences.

Earlier this year, KRN5500 received orphan status for the treatment of chemotherapy-induced neuropathic pain refractory to conventional analgesics in patients with cancer.

“It is noteworthy in this regard that up to 20% of myeloma patients have intrinsic peripheral neuropathy, an incidence that increases to the range of 75% in patients treated with neurotoxic drugs such as thalidomide or bortezomib,” said David J. Drutz, MD, chief executive officer and chief medical officer of DARA BioSciences, in a statement.

In 2011, KRN5500 was granted a fast-track designation, a process designed to facilitate development and to expedite the review of drugs to treat serious conditions and fill an unmet medical need.FDA-Logo

The therapeutic potential of KRN5500 has been demonstrated in vitro and in vivo. The agent, which is a spicamycin derivative, exhibits antimyeloma effects by impairing both myeloma cells and osteoclasts, the company reports.

The orphan drug designation is “an important step toward the potential treatment of multiple myeloma and one of its major complications,” Dr. Drutz said. It will also help in the company’s “ongoing pursuit of partnering opportunities to assist in funding the clinical advancement and development pathway of KRN5500.”

Dr. John S. Macdonald comments on this important FDA decision…
“The fast tracking of this spicamycin derivative recognizes an agent that not only possesses anti cancer (multiple myeloma) activity likely to be beneficial in patients resistant to standard treatment, but also has the potential to decrease a very serious complication of myeloma, bone fractures because it inhibits osteoclast activity.”

SOURCE: Original article by Megan Brooks for MedScape – http://www.medscape.com/viewarticle/826882

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Immune Manipulation in Cancer Treatment: From Wishful Thinking to Tumors Shrinking

Colin Weekes MD PHD AGICCDr. Colin D. Weekes, Ph.D, PI at UC Denver for The Academic GI Cancer Consultant Consortium (AGICC) of The Oncology Consortia of CRITERIUM, INC.

The Holy Grail of cancer therapy has been to cause tumors in patients to disappear with minimal adverse effects on normal tissues. It has been clear, in concept, that one way to achieve this end would be to use the specificity implicit in the human immune system to recognize and destroy cancer cells while sparing normal cells.

Over the last 40 years there have been many attempts to stimulate the immune system in cancer patients in the hope that the this nonspecific stimulation would cause the immune system to recognize and destroy cancer cells. The literature is peppered with trials using non-specific immune stimulating adjuvants like BCG (Bacillus Calmette Guerin). Although some studies suggested some traces of antitumor activity, the overall assessment was negative. Dramatic and clinically meaningful responses didn’t occur. Other approaches to stimulate immunity by infusing patients with cells thought to have antitumor activity using auto and allogeneic stem cell transfer were both toxic and clinically disappointing. The adoptive transfer lymphoid cells, which had been ‘educated’ in vitro to recognize and destroy patient’s cancers (IL2/LAK and TIL infusions) tended to be very toxic. Although significant responses occurred, they were rare and were obtained with toxic side effects that were frequently very severe.

Recently, there have been examples of more significant, more specific and more sophisticated Chemistry behind cancer researchimmune manipulation that may be the leading edge of immune therapies that will be widely applicable to patients with cancer. What may be a ‘breakthrough strategy’ of immune manipulation in cancer has been demonstrated in melanoma. The FDA recently approved the monoclonal antibody Ipilimumab for use in patients with metastatic melanoma. This therapy is unique because its mechanism of action is to increase T-cell antitumor activity by blocking factors suppressing T-cell antitumor activity. Thus the intrinsic antitumor immunity in patients is allowed to function and results in meaningful clinical results (improved survival). Ipilimumab has the capability of producing autoimmunity since it blocks suppression of immune activity. However, clinical toxicity seems manageable. Other types of cancer may benefit from Ipilimumab or therapies with a similar mechanism of action.

The second example of a very intriguing immune manipulation in cancer has been reported this week from Rosenberg and colleagues work at the NCI. This group has been studying Adoptive Cell Transfer (ACT) in patients with metastatic cancer for the last 35 years. ACT, although frequently very toxic especially when given with high dose interleukin-2 (IL2), occasionally resulted in tumor regression. Rosenberg’s group now report results in a patient with metastatic bile duct carcinoma who had had very meaningful tumor responses to ACT using a subset of TIL (Tumor Infiltrating Lymphocytes) selected to be cytotoxic to cancer cells carrying a mutation, ERBB2, of an ERBB2 interacting protein. Toxicity of ACT in this setting is manageable and the patient’s performance status after therapy is excellent.

So why be excited about Ipilimumab and the admittedly, very early results of the newest iteration of ACT from the NCI group? First, the use of immunotherapy may be able to circumvent inherent chemotherapy resistance. Secondly one can imagine that ACT with specific tumorcidal T-cells might combine very nicely with Ipilimumab like agents which enhance T-cell mediated tumor cell death. Further evaluation of this strategy may warrant further testing.

Maybe, indeed, we are leaving the age of wishful thinking and are closing in on a new age of tumor shrinkage in the immune therapy of cancer.

For more information on the consortia model for drug development in oncology trials, please visit our webpage for AGICC and AMyC.

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A Novel Drug for Treatment of Necrotizing Soft-Tissue Infections

Criterium, Inc., a full-service CRO is proud to be the CRO of record as the supplier of services and support for this important trial. Further study details are provided by the pharmaceutical development sponsor, AtoxBio Ltd. on ClinicalTrials.gov

Clincial Trial Results ReportA complete article detailing the trial and its current progress was highlighted in JAMA’s April 2014 issue in print and online (http://archsurg.jamanetwork.com/article.aspx?articleid=1859986). This is a study to evaluate the safety and pharmacokinetics profile of different doses of AB-103 administered to patients diagnosed with Necrotizing Soft Tissue Infections that are scheduled for an urgent surgical intervention as part of their standard of care. The primary study hypothesis is that AB-103 can be administered safely to the patients presenting with Necrotizing Soft Tissue Infections. Secondary endpoints are efficacy by exploratory descriptive analyses of specific efficacy endpoints from three outcome domains to demonstrate treatment benefit of AB-103 in comparison to placebo in patients with Necrotizing Soft Tissue Infections.

The efficacy domains Lab-Beakersare:

  1. Clinical status domain
  2. Pharmacoeconomics domain
  3. Systemic and local inflammatory biomarker domain

Criterium, with extensive experience in dermatology and infectious disease indications, particularly with wound and burn treatments, provided services for data and project management, clinical and medical monitoring, biostatistics, safety, regulatory support, and medical writing.

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When LESS is MORE in Drug Development

Dr J S Macdonald MDDr. John S. Macdonald
Senior Consultant for The Academic GI Cancer Consultant Consortium (AGICC) & The Academic Myeloma Consortium (AMyC) of The Oncology Consortia of CRITERIUM, INC.

Cancer clinical therapy development is moving beyond the classical clinical research trial paradigm used to develop new oncology treatments. This paradigm was based upon the sequential use of Phase I trials to define toxicity and tolerable doses and schedules. Phase II trials then search for signals of efficacy in particular disease types. Phase III trials complete the paradigm and are designed to test new therapies against the current standards of care. Therapies successfully completing the Phase I, II, and III trials are presented to regulatory agencies for approval as widely available cancer treatments.

Although there will always be a role for some drugs to be developed using the classic Phase I-III Test Tube Glowingmechanism for development, many newer cancer treatments will be targeted not against a cancer type but rather against specific molecular targets that may be identified in cancers arising in various different organs. Therefore it doesn’t make sense to do Phase I-III clinical trials in large number of patients with a histologically defined cancer (lung cancer, breast cancer, renal cancer, for example). Rather one needs to test the efficacy of a targeted therapy in tumors that carry the target of interest.

An example of this scenario is the HER2 target. HER2 was originally identified in breast cancer and a monoclonal antibody targeting HER2 (Herceptin) was developed and shown to be efficacious in HER2+ breast cancer. More recently HER2 was identified in about 20% of stomach cancers. Herceptin was shown to be active in HER2+ gastric cancer but not in the roughly 80% of tumors that were HER2-.

Lab BeakerThe gastric cancer HER2 story illustrates important points about targeted therapy development. First, clinical trials taking all comers with a histologically defined cancer like stomach cancer makes no sense. The patient population chosen must be from the 20% of patients whose stomach cancers express HER2. Also full toxicity evaluations and dose finding studies do not need to be done since we have much of these data from the experience with Herceptin in breast cancer.

The bottom line here is that as we get increasingly more sophisticated in defining molecular targets in cancer, we will be dealing with smaller clinical trials performed in carefully defined patient populations. The molecular biology of the cancer and the targeted therapy will be come increasingly more important in cancer therapy development.

For more information on the consortia model for drug development in oncology trials, please visit our webpage for AGICC and AMyC.

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