Creatinine clearance is associated with toxicity from molecularly targeted agents in phase I trials

Oncology. 2012;83(4):177-82. doi: 10.1159/000341152. Epub 2012 Aug 7.

Abstract

Objectives: This study aimed to evaluate any correlations between baseline creatinine clearance and the development of grade 3/4 toxicities during treatment within oncology phase I trials of molecularly targeted agents where entry criteria mandate a serum creatinine of ≤ 1.5 × the upper limit of normal.

Methods: Documented toxicity and creatinine clearance (calculated by the Cockcroft-Gault formula) from all patients treated with molecularly targeted agents in the context of phase I trials within our centre over a 5-year period were analyzed.

Results: Data from 722 patients were analyzed; 116 (16%) developed at least one episode of grade 3/4 toxicity. Patients who developed a late-onset (>1 cycle) grade 3/4 toxicity had a lower creatinine clearance than those who did not (82.69 ml/min vs. 98.97 ml/min; p = < 0.001).

Conclusion: Creatinine clearance (even when within normal limits) should be studied as a potential factor influencing late toxicities in the clinical trials of molecularly targeted anti-cancer drugs.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects*
  • Creatinine / blood
  • Creatinine / pharmacokinetics*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / adverse effects*
  • Prognosis
  • Retrospective Studies
  • Young Adult

Substances

  • Antineoplastic Agents
  • Creatinine