What does a modified-Fibonacci dose-escalation actually correspond to?
نویسندگان
چکیده
BACKGROUND In most phase I oncology trials, it is often stated that the dose increments follow a "modified-Fibonacci sequence". This term, however, is vague. METHODS To better characterize this sequence, we reviewed 81 phase I trials based on this concept. RESULTS Out 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. CONCLUSION This confusing term should be avoided.
منابع مشابه
A Population-Based Clinical Trial of Irinotecan and Carboplatin
Purpose. Phase I trials of anticancer drugs are commonly conducted using the method of modified Fibonacci. We have developed a population-based design for phase I trials of combining anticancer drugs such as irinotecan and carboplatin. Patients and Methods. Intrapatient dose escalation of irinotecan and carboplatin was performed according to a predetermined schema to reach individual dose-limit...
متن کاملInnovations in phase 1 trial design: where do we go next?
In this issue of Clinical Cancer Research, Dees et al. (1) describe the use of PGDE (2) in a Phase 1 trial of CI-958. PGDE was proposed (2, 3) as a more informative and efficient alternative to the standard design for Phase 1 studies (“modified Fibonacci”). Compared with the modified Fibonacci design, the authors estimate that the use of PGDE in this trial required 15–18 fewer patients. All of ...
متن کاملEscalation with Overdose Control is More Efficient and Safer than Accelerated Titration for Dose Finding
The standard 3 + 3 or "modified Fibonacci" up-and-down (MF-UD) method of dose escalation is by far the most used design in dose-finding cancer trials. However, MF-UD has always shown inferior performance when compared with its competitors regarding number of patients treated at optimal doses. A consequence of using less effective designs is that more patients are treated with doses outside the ...
متن کاملA phase I clinical trial of dose escalation of lobaplatin in combination with fixed-dose docetaxel for the treatment of human solid tumours that had progressed following chemotherapy
In this study, the maximum tolerated dose (MTD) of lobaplatin (LBP) when it was combined with docetaxel (TXT) for the treatment of solid tumours that had progressed following chemotherapy was determined, and toxicities to this regimen were evaluated. A modified Fibonacci method was used for the dose escalation of LBP. The patients received TXT (at a fixed dose of 60 mg/m2) on day one (d1) and L...
متن کاملPhase I pharmacokinetic and pharmacodynamic study of a new anthrapyrazole, CI-937 (DUP937).
We performed a phase I trial of CI-937 (DUP937), an anthrapyrazole, with the following objectives: (a) to determine the maximally tolerated dose in humans; (b) to define the toxicity spectrum of this agent; (c) to describe the pharmacokinetics of the drug; (d) to test a pharmacokinetics based hypothesis of dose escalation; and (e) to relate drug pharmacokinetics to pharmacodynamics. CI-937 was ...
متن کامل