What does a modified-Fibonacci dose-escalation actually correspond to?

BMC Med Res Methodol. 2012 Jul 23;12:103. doi: 10.1186/1471-2288-12-103.


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.

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Clinical Protocols
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Dosage Calculations*
  • Humans
  • Maximum Tolerated Dose
  • Neoplasms / drug therapy*
  • Research Design


  • Antineoplastic Agents