Abstract
BackgroundIn most phase I oncology trials, it is often stated that the dose increments follow a “modified-Fibonacci sequence”. This term, however, is vague.MethodsTo better characterize this sequence, we reviewed 81 phase I trials based on this concept.ResultsOut of 198 phase I oncology trials, 81 (41%) are based on modified-Fibonacci series. Actual incremental ratios varied in a large range from 0.80 to 2.08. The median of actual increments was about 2.00, 1.50, 1.33, 1.33, 1.33, 1.33, 1.30, 1.35…. The “modified Fibonacci-sequence” gathers heterogeneous variation of the genuine sequence, which does not tend to a constant number at higher dose-levels.ConclusionThis confusing term should be avoided.
Highlights
In most phase I oncology trials, it is often stated that the dose increments follow a “modifiedFibonacci sequence”
Dose-finding phase I trials seek to determine an optimal recommended dose for a new compound for further testing in phase II trials [1,2]. This dose corresponds to the highest dose associated with an acceptable level of toxicity, referred to as the maximal tolerated dose (MTD)
The phase II recommended dose is usually taken as the dose level just below the MTD [1,2]
Summary
In most phase I oncology trials, it is often stated that the dose increments follow a “modifiedFibonacci sequence”. Dose-finding phase I trials seek to determine an optimal recommended dose for a new compound for further testing in phase II trials [1,2]. For cytotoxic drugs, this dose corresponds to the highest dose associated with an acceptable level of toxicity, referred to as the maximal tolerated dose (MTD). There are two approaches for guiding the number of patients enrolled at each dose level: algorithm-based methods such as the classical 3 + 3 and more recent model-based
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