The Drug-Dosing Conundrum in Oncology — When Less Is More

Shah, Mirat; Rahman, Atiqur; Theoret, Marc R.; Pazdur, Richard

doi:10.1056/nejmp2109826

Cited by 172 publications

(144 citation statements)

References 4 publications

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“…The Oncology Center of Excellence (OCE) in FDA has started its initiative called “Project Optimus” to reform the dose optimization and dose selection paradigm in oncology drug development [ 6 7 ]. FDA wants oncology drug developers to determine the adequate dose and schedule for molecularly targeted agents, not based on the dose finding method for cytotoxic chemotherapeutics, before initiating registration trials.…”

Section: Project Optimus: Fda Initiatives To Support Dose Optimizationmentioning

confidence: 99%

FDA initiatives to support dose optimization in oncology drug development: the less may be the better

Moon¹

2022

Transl Clin Pharmacol

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Section: Project Optimus: Fda Initiatives To Support Dose Optimizationmentioning

confidence: 99%

FDA initiatives to support dose optimization in oncology drug development: the less may be the better

Moon¹

2022

Transl Clin Pharmacol

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“…For example, a least effective dose of 4 mg/kg daily curcuminoids blocked joint swelling in a rat arthritis model in our laboratory, yielding no greater effect at a higher dose, with a similar inhibitory effect documented with an oral HED of 1 g/d ( Figure 2 ). As even oncologic drugs are sometimes insufficiently studied to determine least effective clinical dose ( 55 ), these types of pre-clinical data can help direct botanical clinical trial design.…”

Section: Choice Of Botanical Product For Studymentioning

confidence: 99%

Perspective on Improving the Relevance, Rigor, and Reproducibility of Botanical Clinical Trials: Lessons Learned From Turmeric Trials

Funk

Schneider

2021

Front. Nutr.

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Plant-derived compounds, without doubt, can have significant medicinal effects since many notable drugs in use today, such as morphine or taxol, were first isolated from botanical sources. When an isolated and purified phytochemical is developed as a pharmaceutical, the uniformity and appropriate use of the product are well defined. Less clear are the benefits and best use of plant-based dietary supplements or other formulations since these products, unlike traditional drugs, are chemically complex and variable in composition, even if derived from a single plant source. This perspective will summarize key points–including the premise of ethnobotanical and preclinical evidence, pharmacokinetics, metabolism, and safety–inherent and unique to the study of botanical dietary supplements to be considered when planning or evaluating botanical clinical trials. Market forces and regulatory frameworks also affect clinical trial design since in the United States, for example, botanical dietary supplements cannot be marketed for disease treatment and submission of information on safety or efficacy is not required. Specific challenges are thus readily apparent both for consumers comparing available products for purchase, as well as for commercially sponsored vs. independent researchers planning clinical trials to evaluate medicinal effects of botanicals. Turmeric dietary supplements, a top selling botanical in the United States and focus of over 400 clinical trials to date, will be used throughout to illustrate both the promise and pitfalls associated with the clinical evaluation of botanicals.

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“…This is an old concept and needs revision in present time of targeted therapy and immunotherapy. 10 According to a Canadian Agency for Drugs and Technologies in Health report, the Canadian authorities have approved the 2 mg/kg every 3-weekly dose of pembrolizumab across all tumors based on the basis of initial pembrolizumab clinical trials and modeling based studies. 8 With the establishment of the equal result of 2 mg/kg every 3 weeks and 200 mg every 3 weeks, there is potential of large cost savings on adopting the 2 mg/kg every 3 weeks as compared to the 200 mg flat dose.…”

Section: Introductionmentioning

confidence: 99%

Pembrolizumab Weight-Based Dosing: Conviction and Lacunae in Adopting a Cost-Saving Approach—A Survey Report

Patel

Akhade

2022

Indian J Med Paediatr Oncol

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Introduction Use of immunotherapy drugs has increased leaps and bounds in the last decade with promising results in some of the cancers. The use is limited in low- and middle-income countries due to cost constraints. Weight-based dosing is one measure adopted by Canada and Israel to reduce cost burden and improve access to immunotherapeutic drugs. Objective We conducted a survey among medical oncologists from India to understand challenges faced in accepting the weight-based dosing of pembrolizumab. Materials and Methods Questionnaire covering various aspects related to use of immunotherapy drugs was made and it was circulated across various social media platforms. Medical oncologists practicing across India were invited to participate in this survey. The issues like access to drugs and awareness about weight-based dosing of pembrolizumab were covered in the survey. Also, the impact of international guidelines on accepting the weigh-based dosing was studied. Results Ninety-nine medical oncologists across India participated in the survey. Only 60% medical oncologists are aware about weight-based dosing of pembrolizumab practiced in other countries. Further, 70% of medical oncologists could not prescribe immunotherapy due to cost factor in majority (90%) of their patients. More than 90% agreed that they will use weight-based dosing of pembrolizumab if the Drug Controller General of India, National Comprehensive Cancer Network, or European Society of Medical Oncologists guidelines endorses weight-based dosing. Conclusion Weight-based dosing of pembrolizumab would be accepted if policy makers and Indian medical oncology societies come together and formulate guidelines. Such guidelines will improve accessibility to immunotherapy drugs and lead to huge cost savings.

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The Drug-Dosing Conundrum in Oncology — When Less Is More

Cited by 172 publications

References 4 publications

FDA initiatives to support dose optimization in oncology drug development: the less may be the better

FDA initiatives to support dose optimization in oncology drug development: the less may be the better

Perspective on Improving the Relevance, Rigor, and Reproducibility of Botanical Clinical Trials: Lessons Learned From Turmeric Trials

Pembrolizumab Weight-Based Dosing: Conviction and Lacunae in Adopting a Cost-Saving Approach—A Survey Report

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