Posted by Claire Sojda on Fri, Jan 06, 2012 @ 02:03 PM
5-fluorouracil and its oral form, capecitabine or Xeloda®, are the cornerstones of treatment of a number of cancers, including colorectal, breast, oesophageal and head & neck. We all know that chemotherapy drugs can be extremely toxic; 15-20% of all patients receiving 5-FU will suffer severe side effects such as nausea, diarrhoea, stomatitis (oral inflammation), and decrease in white cells, among others. Up to 5% of patients will suffer extremely severe side effects and some will die as a consequence of their treatment.
Chemotherapy drugs, like all ingested or infused substances, are absorbed, distributed, metabolised and excreted from the body over time. For 5-FU, this process occurs very quickly – less than 5% of the drug remains in a patient’s bloodstream after one hour. Failure of this breakdown process means that systemic 5-FU levels quickly build up, leading to serious toxicity in 3% - 5% of patients. About 1% of the population is estimated to potentially suffer lethal consequences from even one dose of 5-FU because their bodies do not eliminate the drug properly.
An enzyme called DPD (dihydropyrimidine dehydrogenase) is believed to be responsible for the breakdown of 5-FU. So, in the past few years, researchers and some clinicians have administered genetic tests to determine whether 5-FU patients are deficient in DPD, leading to the risk of toxicity or death. But, apparently DPD does not tell us the whole story because some patients who show normal DPD levels go on to develop serious toxic side effects and others who have impaired DPD levels do not exhibit toxicity. In fact, the DPD test has been shown to correctly predict the risk of toxicity 50% of the time. As good as tossing a coin!
Saladax Biomedical Inc have developed a simple blood test for the measurement of 5-FU in plasma that can be easily performed by the routine hospital laboratory. Workers in Italy and the Netherlands have been developing a simple “5-FU clearance test”. The test is very simple: a very small dose of 5-FU (a fraction of the full dose that would not be enough to cause any harm) is administered to the patient and about one hour later a blood sample is taken and the 5-FU levels are measured. Since most of the 5-FU is typically excreted from the body within one hour, a patient with normal metabolic activity will have dramatically low blood levels of the drug. Patients who have a 5-FU clearance impairment will have elevated levels of 5-FU in their blood. With this information, the doctor can decide whether 5-FU is the drug of choice for his/her patient, and whether standard dosing should be modified to avoid undue toxicity.
We are excited to be involved in the development of this 5-FU clearance test as it represents a very simple, cost effective, practical approach to predicting 5-FU toxicity and helping to save lives and improve the quality of life for cancer patients during treatment.
Paul Kenny, European Key Account Manager
Posted by Claire Sojda on Fri, Dec 16, 2011 @ 02:05 PM
Achieving and maintaining the optimal therapeutic range through administering the maximum tolerated dose (MTD) is often not followed by physicians. Though MTD is the widely accepted standard for chemotherapy treatment, what concerns physicians are the severe toxic side effects that may result. Consequently patients receive dosages that are often either too high or too low. Neither result is beneficial or promising. Too high of a dosage can result in toxicity, compromised immunity, and higher treatment costs while too low of a dosage can mean a lack of therapeutic response, continued growth of cancer, and higher cost of reoccurrence.
With Saladax's My5-FU blood test, oncologists can determine the optimal dose of chemotherapy for each individual cancer patient. Many fields of medicine practice dose optimization. The time is right for oncology to get on board!
Posted by Adrienne Choma on Fri, Sep 30, 2011 @ 09:23 AM
A study was just published last month in the Clinical Colorectal Cancer journal (Vol. 10, No. 3, pp. 203-206, September 2011) that again reaffirms the need for a personalized approach to dosing 5- fluorouracil (5-FU) for colorectal cancer patients.
Myriad Genetics of Salt Lake City, Utah, a specialty oncology laboratory, studied 357 colorectal cancer patients being treated with various drug regimens containing 5-FU to assess the effectiveness of currently accepted dosing based upon Body Surface Area (BSA). They found that when patients’ 5-FU dose is based on the current standard of care, only 21 percent of the patients achieved the target systemic drug exposure determined to provide optimal treatment efficacy. Fifty-one percent of patients were found to have insufficient drug in their bloodstream to effectively battle their cancer – they were under-dosed. And 28 percent were found to be over-dosed, which results in undue toxicity, reduced quality of life and may occasion the need for “drug holidays” because patients can’t tolerate their treatment.
Therefore the study showed that as a typical colorectal cancer patient, you only have a one-in-five chance to get the right amount of drug needed to effectively treat colorectal cancer. That’s not very encouraging! Clearly there is a need for personalized dosing.
Adrienne Choma, Founder & VP of Marketing & Sales
Posted by Adrienne Choma on Wed, Aug 31, 2011 @ 06:08 PM
The recent change in Facebook policy taking away the ability to block public comments on a wall has caused some pharmaceutical and biotech companies to shut down their Facebook pages. Concerns over the implication of open walls on regulatory compliance issues are real, especially in light of the lack of FDA clarity on social media communications. However, we feel that it is important that the public have the opportunity to openly and honestly express their views, share their experiences, and ask questions on new technologies that are so rapidly becoming available to the medical community. Saladax is committed to maintaining the policy of an open wall which was available since inception of our corporate page.
To view and become a fan of the Personalized Medicine & Dose Optimization – Saladax Biomedical Facebook page please use the following link: https://www.facebook.com/SaladaxBiomedical
Posted by Adrienne Choma on Mon, Aug 01, 2011 @ 01:54 PM
By its very definition, chemotherapy is toxic. Its job is to kill cancer cells, but unfortunately these agents do not discriminate between cancer cells and healthy cells, and as a consequence, some devastating side effects might ensue. If you look at the National Cancer Institute's common toxicity criteria, you will find a terrifying 70+ page document dedicated solely to describing and grading the various side effects associated with chemotherapy!
Chemotherapy side effects are graded from 1 to 5, with 1 being the mildest, even asymptomatic, to 5 being the most severe, even fatal! For obvious reasons, oncologists strive to minimize side effects of chemotherapy. When a patient exhibits Grade 3 or higher toxicity, oncologists may reduce the dose of the chemotherapeutic drug in the next treatment cycle, delay the next treatment or even discontinue treatment with that particular drug.
However, not everyone who receives chemotherapy will suffer toxic side effects or experience them to the same degree of severity. Many personal factors such as age, metabolism, liver function, kidney function, tumor size, drug absorption and clearance, as well as genetic factors influence the way a drug interacts with an individual’s cells. It is impossible to predict, in advance of drug administration, how all these factors will interact and how well a patient will tolerate and respond to the chosen chemotherapeutic treatment.
But of course doctors want to ensure that their patients are getting the right amount of drug to kill the cancer without unnecessary suffering due to toxic side effects. Arbitrarily reducing the dose may result in drug blood levels insufficient to kill the cancer. Delaying or discontinuing treatment may deprive the patient of an important weapon in the fight for survival. The oncologist is forced to walk a metaphorical tightrope when prescribing these drugs, and is locked into a major conflict!
Saladax Biomedical developed a simple tool to assist oncologists in optimizing individual patient chemotherapy dosing. The company specializes in the development of simple blood tests that can measure chemotherapy agents, so that oncologists can see the actual levels of the drug circulating in their patients’ blood stream and titrate the dose to a pre-defined optimal level – the so called therapeutic window. This window is the concentration of drug in the patient's blood that is considered to be most effective with the least side effects – you might call it the “sweet spot”. This has been demonstrated with the My5-FU™ test from Saladax. 5-fluorouracil (5-FU) is a drug commonly used for the treatment of a number of cancers, that whilst highly effective is associated with some fairly harsh side effects. Clinical research conducted in Europe has demonstrated that 5-FU dose optimization in colorectal cancer patients can significantly reduce grade 3 and 4 toxicities and improve treatment response rates.
This new tool can significantly improve the safety and effectiveness of 5-FU for cancer patients. Saladax is committed to bringing more blood tests for chemotherapy agents to the market to help one day win the ongoing battle against cancer.
Paul Kenny, European Key Account Manager
Posted by Adrienne Choma on Tue, Jul 05, 2011 @ 01:10 PM
Do you know how pharmaceutical companies determine the prescribed dose for new drugs? It’s really pretty scary! The maximum tolerated dose (MTD) for a new cancer drug is established in Phase I clinical trials, often using the Fibonacci 3+3 Schema.
It works like this: First, several dosing levels are targeted by the pharmaceutical company for testing. Three patients are administered the new drug at each of these targeted dosing levels. If one of the three patients at any dose level displays undue toxicity, an additional three patients are administered the drug at the same dose. If one of the three new patients again displays high toxicity, the next lower dosing level being tested in the Phase I clinical trial becomes the recommended dose.
What this means is that the recommended dose of a new drug can be established on the basis of testing only six patients!
Given that there can be more than a 10-fold variability in drug blood levels of patients receiving the identical dose of a chemotherapy drug, this hardly seems justifiable or clinically sound. It can also help explain why cancer drugs are not as effective in combating disease as they could be. The pharmaceutical industry offers us a lot of beneficial drugs – but often, they can be more effective if dosed correctly to meet the needs of the individual patient. The body of knowledge in pharmacokinetics and newly available dose monitoring tools are now available to make personalized dosing a reality for better patient care.
Adrienne Choma, Vice President, Marketing & Sales
Posted by Adrienne Choma on Tue, Jun 21, 2011 @ 11:57 AM
With all the advances in oncology and the recent focus on “Personalized Medicine,” why are pharmaceutical companies and oncologists still using this crude dosing methodology that cannot compensate for the complexities of an individual and has been proven to be woefully inadequate to ensure that patients receive optimal treatment?
In truth, it is because there have been no practical alternatives available for oncology drug dosing. In other fields of medicine, such as cardiology, treatment of epilepsy and more recently, transplantation medicine, doctors can ensure that their patients are receiving the optimal dose through a simple blood test to measure the concentration of the drug in the patient’s plasma. This practice has been around for more than forty years and is known as Therapeutic Drug Monitoring or Therapeutic Drug Management (TDM).
It seems an obvious solution; however it has only been recently that simple lab tests have become available to measure oncology drug levels in cancer patients’ blood. Saladax Biomedical is a company dedicated to the development of such assays, allowing the routine measurement of chemotherapy drugs from a simple blood test. Saladax has a portfolio of thirteen oncology drug management assays in their portfolio and the first test made available to oncologists is for 5-fluorouracil (5-FU), which is commonly used to treat colorectal cancer and other solid tumors.
Clinical studies have demonstrated that a very high percentage of 5-FU patients do not get the best dose of this drug. 40% to 60% of patients are under-dosed (which leads to less than effective treatment of the cancer and potential relapse of disease) and another 10% to 20% of patients are over-dosed (leading to excessive toxic side effects that cause treatment termination and serious impairment of quality of life). Less than 25% of patients dosed by BSA receive the optimal dose to most effectively deal with their cancer.
Now, there is a better way.....
Paul Kenny, European Key Account Manager
Posted by Adrienne Choma on Fri, Jun 17, 2011 @ 01:11 PM
Body surface area (or BSA) is a formula used by physicians for determining the amount of drug to administer to a patient when the drug has a narrow therapeutic window (i.e., the amount of the given drug that causes a therapeutic effect is very close to the amount that causes toxic side effects). Chemotherapy drugs fall squarely into this description. BSA is based upon a calculation of an individual patient’s body mass based upon their height and weight.
BSA is a fairly simple albeit imperfect calculation that has endured over the years and today is still regularly applied in the field of oncology. It is quite remarkable that despite the massive investment and significant advances in cancer research, BSA is still the standard of care in dosing chemotherapy drugs. The pharmaceutical industry and medical community has learned much about pharmacokinetics (the study of the impact a body has on an administered drug, i.e., the mechanisms, rate of absorption and distribution of an administered drug), but has not effectively applied this knowledge in advancing cancer drug dosing to meet personal patient needs.
A simple analogy we can all relate to is ten people drink a whole bottle of wine in one sitting. As you can imagine, regardless of their body mass, there will be a wide range of results among these folks - from remaining totally sober to becoming extremely inebriated! The reasons for this interpersonal variation are many, and factors include - if or what they last ate, if they are avid drinkers or not, fitness, age, sex and so on. We all appreciate this variability in individual tolerances – it is not rocket science!
An enduring characteristic of cancer is that everyone’s disease is different and it is well recognized that the best results are achieved when treatment is tailored to the individual. Unfortunately, when doctors dose by BSA they administer the same amount of drug to all patients disregarding interpatient variability of greater than ten-fold that is well established in clinical studies. This means that one patient may have ten times more drug or ten times less drug coursing through their system than the next patient – while the doctor believes that he/she has administered the right dose! It is clear that “one size does not fit all” when administering cancer drugs.
Paul Kenny, European Key Account Manager
Check back next week for Mr. Kenny's Part II blog post on body surface area where he will reveal a better approach for managing chemotherapy drug dosing in patients.
Posted by Adrienne Choma on Fri, Jun 10, 2011 @ 04:00 PM
I recently wrote about the shortcomings of Body Surface Area (BSA) based dosing of chemotherapy drugs. A study just published in Clinical Colorectal Cancer has reaffirmed that BSA dosing of 5-fluorouracil for colorectal cancer patients receiving FOLFOX treatment regimens is suboptimal in ensuring that patients are administered the right dose for treatment efficacy.
This study analyzed the 5-FU plasma concentrations of 357 patients who were dosed based upon BSA. Over 50% of these patients received too little drug to reach the plasma target range and another 28% were above the target range. Only 21% of patients were found to have drug plasma levels within the target range with BSA dosing. Prior studies have shown that patients whose plasma drug levels are within target range realize better treatment outcomes and suffer lower toxic side effects associated with chemotherapy drugs.
Why is there such wide variation in drug plasma concentrations among patients? BSA dosing is based solely upon body mass and does not take into account the many factors that impact drug metabolism, including age, gender, disease state, drug-drug interactions, genotype and organ function.
Sixty-two of the patients in the study had their 5-FU doses personalized during the course of treatment to reach the drug plasma target range. Of these 62, only 5% were within target range at the beginning of the study and over 50% were outliers. After four rounds of adjusted dosing, 37% were within target and only 14.5% were outliers.
OnDose®, the simple blood test that enables oncologists to determine whether their patients are being over- or under-dosed is being offered in the United States by Myriad Genetics.
Adrienne Choma, Vice President, Marketing & Sales
Posted by Adrienne Choma on Wed, Jun 01, 2011 @ 09:00 AM
Colorectal cancer is the third most common cancer in the world, with over 1.23 million new cases diagnosed annually. More than 600,000 people die of colorectal cancer every year. Why isn’t treatment more effective?
One reason may be that the drugs used to treat colorectal cancer are not used in the best way possible. A Phase III randomized study published by Dr. Erick Gamelin in the Journal of Clinical Oncology in 2008 found that 85% of 208 patients in the study did not receive the right dose of the critical chemotherapy drug, 5-FU, to get best clinical outcomes and reduce the nasty toxic side effects associated with chemotherapy. Surprisingly, 67% of the patients were underdosed – they did not appear to get enough drug to effectively kill their cancer cells. The other 18% were overdosed, which could lead to undue toxicity.
Those patients in the study who received personalized dosing adjustments to reach the optimal systemic exposure to 5-FU realized almost a doubling in response to treatment, 2-year overall survival and dramatically reduced toxic side effects.
Achieving these greatly improved treatment results only takes a simple blood test that will help oncologists target the right dose for their individual patients. To find out more about these blood tests please visit the Products section of our website.
Adrienne Choma, Vice President, Marketing & Sales