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Creatinine clearance is associated with toxicity from molecularly targeted agents in phase I trials
B Basu1, J Vitfell-Pedersen, V Moreno Garcia
1Drug Development Unit, Division of Clinical Studies, The Institute of Cancer Research/The Royal Marsden NHS Foundation Trust, Sutton, UK.
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.
Insights
Lower baseline creatinine clearance, even within normal limits, is linked to increased late-onset severe toxicities in oncology patients receiving molecularly targeted agents during phase I trials.
Area of Science:
- Oncology
- Pharmacology
- Nephrology
Background:
- Phase I clinical trials for molecularly targeted agents often have creatinine clearance criteria.
- Understanding factors influencing toxicity is crucial for patient safety and trial design.
Purpose of the Study:
- To investigate the correlation between baseline creatinine clearance and the incidence of severe (grade 3/4) toxicities.
- To determine if baseline kidney function impacts the development of late-onset toxicities in patients receiving targeted cancer therapies.
Main Methods:
- Retrospective analysis of 722 patients from phase I trials of molecularly targeted agents.
- Creatinine clearance was calculated using the Cockcroft-Gault formula.
- Toxicity data and patient creatinine levels were collected over a 5-year period.
Main Results:
- 16% of patients (116/722) experienced grade 3/4 toxicity.
- Patients developing late-onset grade 3/4 toxicity had significantly lower baseline creatinine clearance (82.69 ml/min) compared to those without (98.97 ml/min).
- The difference in creatinine clearance was statistically significant (p < 0.001).
Conclusions:
- Baseline creatinine clearance, even within normal ranges, may predict the risk of late-onset severe toxicities.
- Further research is warranted to explore creatinine clearance as a predictive biomarker for toxicity in targeted cancer drug trials.
- These findings could inform patient selection and monitoring in future clinical trials.
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