82. Dosage of chemotherapy can be difficult: If the dose is too low, it will be ineffective against the tumor, whereas, at excessive doses, the toxicity (side-effects) will be intolerable to the patient. The standard method of determining chemotherapy dosage is based on calculated body surface area (BSA). The BSA is usually calculated with a mathematical formula or a nomogram, using a patient’s weight and height, rather than by direct measurement of body mass. This formula was originally derived in a 1916 study and attempted to translate medicinal doses established with laboratory animals to equivalent doses for humans. The study only included 9 human subjects. When chemotherapy was introduced in the 1950s, the BSA formula was adopted as the official standard for chemotherapy dosing for lack of a better option.
Recently, the validity of this method in calculating uniform doses has been questioned. The reason for this is that the formula only takes into accounts the individual’s weight and height. Drug absorption and clearance are influenced by multiple factors, including age, gender, metabolism, disease state, organ function, drug-to-drug interactions, genetics, and obesity, which has a major impact on the actual concentration of the drug in the patient’s bloodstream. As a result, there is high variability in the systemic chemotherapy drug concentration among patients dosed by BSA, and this variability has been demonstrated to be more than 10-fold for many drugs. In other words, if two patients receive the same dose of a given drug based on BSA, the concentration of that drug in the bloodstream of one patient may be 10 times higher or lower compared to that of the other patient. This variability is typical with many chemotherapy drugs dosed by BSA, and, as shown below, was demonstrated in a study of 14 common chemotherapy drugs.
The result of this pharmacokinetic variability among patients is that many patients do not receive the right dose to achieve optimal treatment effectiveness with minimized toxic side effects. Some patients are overdosed while others are underdosed. For example, in a randomized clinical trial, investigators found 85% of metastatic colorectal cancer patients treated with 5-fluorouracil (5-FU) did not receive the optimal therapeutic dose when dosed by the BSA standard— 68% were underdosed and 17% were overdosed.
There has been recent controversy over the use of BSA to calculate chemotherapy doses for obese patients. Because of their higher BSA, clinicians often arbitrarily reduce the dose prescribed by the BSA formula for fear of overdosing. In many cases, this can result in sub-optimal treatment.
What is the closest meaning of the word “derived” in line 7?
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