“Personalized Drug Dosing”

erated dose, and not the minimum effective dose. This becomes incorporated into practice as the “standard of care”. Note that this is standard care and not necessarily the “gold-standard” or optimal care. The conditions for drug approval are different from the conditions for a given patient. For example, they don’t consider body differences, such as the effective dose for a 250 lb.

“Personalized Drug Dosing” (Paul Van Camp and Jeff Krolick) [#68] bodybuilder vs. the effective dose for a 90 lb. person with sarcopenia (loss of muscle tissue as a natural part of the aging process). Maximum tolerated continuous dosing of any cancer therapy that does not promptly and completely cure the cancer inevitably leads to its own failure by selecting for resistance.

It is true for chemotherapies, and it is true of hormonal and immunotherapies. Many drugs can be effective at lower doses with less side effects, such as the androgen deprivation drug abiraterone at 250 mg vs. 1000 mg daily when taken with a moderate fat breakfast (per the FDA).

Other prostate cancer drugs, such as enzalutamide, can have terrible side effects such as severe fatigue for some, and have now demonstrated effectiveness at half the dosage (per many medical oncologists, including prostate cancer expert Dr. Oliver Sartor). The same may be true for other prostate cancer drugs, such as apalutamide and darolutamide.

Indeed, preliminary evidence shows that the effective dose of darolutamide is not the maximum tolerated dose that is frequently used. Unfortunately we usually do not have adequate data for minimal effective dosages. This typically emerges slowly from real-world experiences.

Many drugs are administered without considering pharmacogenomics – that different people metabolize drugs at different rates. A diagnostic test may be able to personalize drug dosing.

The Solution - What You Should Do To fully personalize cancer care, patients and their doctors must leverage patient data not only to identify the right therapy, but also to determine the precise dose that will maximize the patient’s benefit-to-risk ratio. Diagnostic technologies to personalize dosing can play a pivotal role in improving patient outcomes.

Patients and their doctors must select effective alternatives to the “maximum tolerated dose until failure” model, including using Darwinian evolutionary dynamics to provide better clinical outcomes, avoid or slow resistance, slow progression of cancer through its developmental stages (“Hallmarks of Cancer”), reduce toxicity and harms of treatment, and improve quality of life while living with a cancer diagnosis.

There are various strategies, but they all involve “switching things up” before the complete failure (resistance) of a treatment.

y all involve “switching things up” before the complete failure (resistance) of a treatment. Dosing should be personalized within a treatment strategy, such as mathematical models based on evolutionary biology, tying drug doses to diagnostic tests on drug response, rather than pre-defined doses and frequency. For example, Dr.

Bob Gatenby described his adaptive therapy study which used evolution-based mathematical models to manage drug frequency, significantly prolonging drug response in metastatic castrate-resistant prostate cancer.

You should educate yourself about personalized dosing and adaptive therapy, and discuss personalized drug dosing with your doctors, checking to see if there is a possibility of a “minimum effective dose” vs. the standard “maximum tolerated dose”.

Since pharmaceutical companies will not be motivated to run a randomized clinical trial to find a minimum effective dose, the way to find a minimum effective dose is to review the real world experience of other patients. The US FDA’s Oncology Center of Excellence is leading an initiative, Project Optimus, to reform the dose optimization and dose selection paradigm in oncology drug development.

It will also have implications for personalized drug dosing for patients in clinical delivery.

“Personalized Drug Dosing” (Paul Van Camp and Jeff Krolick) [#68] Advanced prostate cancer patients Dr. Paul Van Camp and Jeff Krolick shared their insights and personal experiences with personalized drug dosing: Patient Views and Cases Dr. Paul Van Camp shared his views on the above issues, including how doses for FDA approval derive from clinical trials: Maximum Tolerated Dose vs.

Minimum Effective Dose; the problem of continuous Maximum Tolerated Dose to failure, hormonal therapies (ADT +/- ARSI) until failure and progression to Castrate Resistant Prostate Cancer, how all Maximum Tolerated Dose administration continuously used will eventually fail (caused by resistance); combination treatments and sequencing strategies to overcome resistance; non-FDA dosing alternatives from real-world clinical experience (e.

g., half dose enzalutamide or darolutamide; Abiraterone at 250mg with fatty breakfast as examples); remembering to check drug-drug interactions (and supplements, and effects on metabolizing enzymes (CYP450 - Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis).

His regimen includes periodic senolytics (drugs that selectively clear senescent cells - which stop multiplying but don't die off when they should), for example, a three-day course every three months and especially after completing some other course of therapy such as radiation, radioligand, or chemotherapy. Jeff Krolick has been microdosing various drugs and supplements to treat his cancer.

ths and especially after completing some other course of therapy such as radiation, radioligand, or chemotherapy. Jeff Krolick has been microdosing various drugs and supplements to treat his cancer. He has been using Adaptive Therapy (and now SBRT for Oligometastatic prostate cancer) as directed by his medical oncologist, Dr. Lemanne, in collaboration with Drs.

Gatenby, Brown and Anderson from the Integrated Mathematical Oncology team at Moffitt Cancer Center and Dr.

Tran from the Radiation Oncology-Biology Integration Network Oligometastasis (ROBIN OligoMET) Center at the University of Maryland Medical Center, which is focused on understanding how radiation therapy can affect the metastatic process particularly in low- volume or oligometastatic prostate cancer.

The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab/Prostate Cancer Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action.

You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health.

“Personalized Drug Dosing” (Paul Van Camp and Jeff Krolick) [#68] Meeting Notes The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab/Prostate Cancer Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action.

You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health. Discussion Outline 1.Paul Van Camp introduction. 2.Dosing of drugs for prostate cancer. (2:49) 3.Effective dose vs. maximum tolerated dose. (6:43) 4.Is there a minimum tolerated dose for prostate cancer? (12:16) 5.

Paul's response to questions. (17:01) 6.Jeff Krolick introduction. (26:09) 7.How do you make cancer extinct by using first and second strike strategies? (32:58) 8.

Mushrooms (41:57) SUMMARY KEYWORDS drug, oncologist, dosing, dose, psa, patients, milligrams, toxicity, cancer, working, paul, regimen, prostate cancer, tolerate, overall survival, personalized, therapy, strike, cells, approved SPEAKERS Paul Van Camp (48%), Jeff Krolick (27%), Brad Power (13%), Amit Gattani (9%), Robert Gurmankin (3%), John Sandiford (<1%) Meeting Transcript Brad Power Today we're going to talk about personalized dosing.

This is a subject which we've covered once before with Mina Nikanjam. She was going to be joining us, but unfortunately is ill and will not be able to.

t Gattani (9%), Robert Gurmankin (3%), John Sandiford (<1%) Meeting Transcript Brad Power Today we're going to talk about personalized dosing. This is a subject which we've covered once before with Mina Nikanjam. She was going to be joining us, but unfortunately is ill and will not be able to. We have two patients who will be talking about their experience with personalized dosing, Dr.

Paul Van Camp and Jeff Krolick. Brad Power 1:19 To set this up, I'll try to give you a few highlights from the meeting description we sent out. Paul will pick up on these ideas as well. The dosing that you get is what the dosing was in the original clinical trial that approved the drug. And therefore the dosing is typically done at maximum tolerable dose.

The way it's applied is typically maximum tolerable dose until failure. There's a possibility that people metabolize medicines differently, and that lower doses might be equally effective and have fewer side effects. So there's a discussion about how you can personalize dosing or reduce dosing based on an individual.

“Personalized Drug Dosing” (Paul Van Camp and Jeff Krolick) [#68] figure out how you would personalize your dosing. You'll hear a couple of stories from our patients who've done that. Brad Power 2:26 We'll start with Paul. Paul is both a trained medical doctor, as well as a prostate cancer survivor, and he is very knowledgeable and very helpful to other patients.

So Paul, why don't you start on your views on drug dosing, personalized dosing, and actually how you've applied it to yourself? Paul Van Camp 2:49 In considering dosing drugs for cancer, in general, and drugs for prostate cancer, specifically, we've seen several new and useful drugs come out into practice than in very recent years.

These drugs are FDA approved, the requirement for FDA approval is that they go through stage one, two, and three clinical trials. Stage one, they take a few patients, and they do escalating doses. They keep pushing the doses and see how much they can get away with until there's an acceptable toxicity, then they take the level right below that, which is acceptable toxicity.

And they test that and fit larger phase two trials to refine it to decide what dosage regimen and is going to go on to stage three, which leads to FDA approval based paths, just statistical analysis of the results over a period of time to an endpoint.

And the endpoint usually is focused on the median patient, meaning if there's 100 patients in a trial that the 50th patient, either a progression free survival or overall survival, so it doesn't look at that bottom 20% or the top 20%. It looks at that theoretical median patient, which doesn't actually it's not actually a real person.

It's a derivation, because for overall survival, they can't wait for the last patient to die. They wait for half the patients to die. pretty brutal.