* MyCare is not available in the United States. Myriad Genetics offers 5-FU does management as OnDose®.

Patient Frequently Asked Questions*

Commonly Asked Questions on Personalized Medicine

1. How does my doctor currently determine how much chemotherapy drug to give me to fight my cancer?

The current standard of care for determining the dose of most chemotherapy drugs is based on body surface area (BSA), a formula that was first derived in 1916 based on the study of only 8 patients. BSA is a “one size fits all” approach to determining your chemotherapy drug dose. It is a mathematical formula for calculating drug dose based only on a patient’s height and weight.

(See the Pharmacokinetics section of our website to learn more.)

2. Is BSA-based dosing of chemotherapy drugs effective?

No. Research shows that BSA-based dosing is ineffective in achieving the right systemic concentration of the drug for best treatment results. Since 1916, we have learned a lot about how people absorb and process substances like food and drugs from their systems. We now know that there are multiple factors that affect the rate of drug clearance and that this rate is variable from one individual to another, with up to a 30-fold difference. For example, your organ function and the state of your disease will impact how your body will process chemotherapy drugs. A more advanced cancer may absorb more drug than a smaller tumor. In addition, factors such as genetics, age, sex, sleeping patterns and drug-drug interactions are all important factors that cause variability from one patient to another.

To get the best treatment benefit, achieving the optimal drug blood concentration is more important than the drug dose that is administered. These breakthroughs in “personalized medicine” are important advances in chemotherapy treatment. Research shows that an optimal drug blood concentration can lead to less serious side effects and better treatment results. While quality of life is not often associated with cancer treatment, it should be the goal of every oncologist who treats cancer. Optimal dosing can improve the overall drug treatment experience.

See Background and Research below for more information on BSA testing and Optimal Dosing.

3. How can I receive the right amount of chemotherapy?

Begin by asking your oncologist whether BSA-based dosing is the best way to ensure that you have the right amount of drug to best battle your cancer, while at the same time reducing the risk of serious toxic side effects. Ask your doctor about Saladax’s MyCare – simple blood tests that will measure how much drug is in your bloodstream. Based on the actual drug concentration in your blood, as well as other signs and symptoms from clinical examinations, your physician will determine if dose adjustments are right for you. Your doctor will adjust subsequent doses of the chemotherapy drug based upon the information provided from the test results.

4. How are the MyCare tests administered?

The MyCare tests are simple blood tests that require either one or two blood draws during the course of your infusional chemotherapy treatment. The dose for your first infusion will be determined based upon your doctor’s current practice – BSA. During your first infusion, the nurse will draw one or two small samples of your blood and send it to the laboratory for analysis. The test measures how much drug is in your bloodstream, which can vary significantly (thirty-fold or more) from one patient to another when receiving the same BSA-dose.

If your drug blood level is not within the optimal target range of blood concentration, an average of three treatment cycles with dose adjustments will be needed to bring the drug levels into target range. The adjustments will be gradual, depending upon how far your levels are from target. Once you are within target range, it is recommended that you have your levels checked at least every three cycles to ensure that the drug concentration remains in range.

The Saladax MyCare assays provide an easy, convenient and cost-effective way to ensure you get the maximum benefit and the highest quality of life out of your cancer treatment.

5. What is personalized medicine & how does it relate to optimal chemotherapy dose management?

Personalized medicine is an increasingly popular approach to healthcare that promises greater precision and effectiveness than traditional medicine because it takes into consideration each person’s unique clinical, social, genetic, genomic, and environmental information in devising a treatment plan. Personalized medicine takes an integrated, coordinated, evidence-based approach to individualizing patient care across the continuum from health to disease.

Several alternative approaches to cancer drug dosing have been studied and proposed. One such approach is therapeutic drug management (TDM). TDM is the measurement and adjustment of drug levels in patients’ blood to achieve the right systemic drug exposure for optimal efficacy and the least toxicity. TDM is not new to the medical community and is standard in many medical fields; it is used routinely with transplantation, antiepileptic and antibiotic drugs. TDM is typically called for where the drug being monitored has a narrow therapeutic window, there is evidence that systemic drug exposure (in your bloodstream) correlates with biological effects such as toxicity or response to treatment, and the drug has the potential to cause dose-limiting toxicity (side effects during treatment that are severe enough to prevent increase in strength of drug, or to prevent continuation of treatment). All these factors are clearly associated with chemotherapy drugs and they are perfect candidates for TDM.

Much of the focus of personalized medicine in the pharmaceutical world is on advances in Pharmacogenomics – the study of how the tumor genes affect a person’s response to drugs. Some individuals will respond to one drug better than another depending upon the tumor genotype. The identification of patients with specific diseases or the drugs to which they will respond through genetic testing is a remarkable and clinically significant advancement. But, identifying the right drug for the right person is only part of the cure. Identifying the right dose of the right drug is equally important and will further enhance treatment efficacy. Pharmacogenomics and TDM should work hand and hand for the most effective personalized treatment, ensuring that patients receive the right drug, at the right dose and at the right time. Chemotherapy TDM provides your doctor with objective information to tailor the dose to your individual profile to give you the highest therapeutic effects with less risk of excessive toxic side effects.

6. Why do so many patients not receive the optimal dose of their chemotherapy drugs today?

Pharmaceutical companies develop dosing recommendations during phase 1 clinical studies of their drugs. How are dosing recommendations established? A common protocol that the pharmaceutical industry has used to determine dose is the Fibonacci 3 + 3 Schema for establishing maximum tolerated dose (the dose that will be recommended in their FDA-approved package insert.). In this protocol, three patients are treated with each of several pre-assumed drug doses during phase 1 clinical trials. If at any dosing level one patient develops dose-limiting toxicity, three more patients are added to the trial at the same dose. If one more of the newly added patients develop dose-limiting toxicity, the maximum tolerated dose recommended by the drug manufacturer is the next lower dosing level that was tested.

In essence, FDA-approved dosing levels can be established on as few as six patients. Given that inter-patient drug blood levels can vary up to 30-fold, it is easy to see that this mechanism for determining optimal dosing is far from precise and is certainly not optimal for most patients. In fact, under this scheme, 66% of patients are likely not to receive the optimal drug dose for best treatment.

Background and Research on BSA and Optimal Drug Dosing:

Numerous studies (see Publications) have concluded that BSA is not a good method of dosing drugs. In a study of 33 cancer drugs between 1991 and 2001, it was found that only 5 of the 33 drugs could be said to reduce interpatient blood level variability when dosed by BSA, and that reduction in variability was only between 15% and 35%.2 This means that at best 65% of the variability in patients’ blood drug levels was due to factors unexplained by BSA-dosing.

A study published in the Journal of Clinical Oncology in 2008 concluded that 85% of metastatic colorectal cancer patients did not receive the correct dose of 5-fluorouracil (5-FU), which is the foundation of treatment regimens for colorectal cancer. Surprisingly, 68% of patients received too little drug to reach optimal therapeutic systemic exposure, leading to sub-optimal treatment efficacy. Another 17% were overdosed, which can result in higher incidence and grade of serious toxic side effects. Only 15% of all colorectal cancer patients in this study received the correct amount of drug when dosed by BSA.3 

In the group of patients who had their 5-FU doses adjusted based upon monitoring of blood levels, there were significantly fewer and less severe toxic side effects. Overall response rate (the percentage of patients whose cancer shrinks [partial response, PR] or disappears after treatment [complete response, CR]) for the dose-adjusted group was 2-fold higher than for the BSA-dosed group and median overall survival was improved by 6 months.3

Eighteen percent of patients who received standard BSA-based dosing of 5-FU experienced grade 3/4 diarrhea, whereas only 4% of those whose dose was adjusted for optimal exposure suffered this serious side effect. Hematologic toxicity was eliminated.

In this same study, patients whose drug dose was adjusted for optimal exposure experienced nearly a doubling of positive response to their treatment.

Dose-adjusted patients also had much higher one and two-year survival rates, with more than double of the BSA-dosed patients surviving after two years.

Docetaxel is another drug for which BSA dosing has been shown to be ineffective in achieving the right exposure. In a study of 640 patients, the rate that docetaxel was cleared  was shown to be a strong independent predictor of the most serious grade 4 and febrile neutropenia. Patients who cleared docetaxel 50% more slowly than average had a 4-fold increased likelihood of suffering from grade 4 neutropenia and a 3-fold increased likelihood of experiencing febrile neutropenia.4 With the high inter-patient variability with BSA-based dosing, doctors cannot predict which of their patients are at risk of these serious side effects until after they happen. It should be clear to all that BSA is not the best way to determine chemotherapy drug dose in this age of personalized medicine.

View a Short Video on My-5-FU

References:

  1. Gamelin E et al. J ClinOncol. 1999;17:1105-1110; Milano G et al. J ClinOncol. 1992;10:1171-1175; Saif, MW et al. J Nat Cancer Inst. 101(22):1543-1552, 2009.
  2. Baker, SD, et al. J Natl Cancer Inst. 94:1883-1888, 2002.
  3. Gamelin, E et al. J ClinOncol. 26:2099-2105, 2008.
  4. Bruno, R et al. J ClinOncol. 16(1):187-196, 1998.
  5. Saam, J et al. Clinical Colorectal Cancer, 10(3):203-206, 2011.
  6. Gamelin, E et al. Clinical Colorectal Cancer, in press.

Helpful Links

American Cancer Society
American College of Gastroenterology (Patient Information)
Cancer.Net
Colon Cancer Alliance
Colorectal Cancer Coalition
Colon Cancer Today
National Cancer Institute
National Comprehensive Cancer Network (For Patients)
Oncology Channel