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


CONCLUSIONS
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.
Drug Development Unit, Division of Clinical Studies, The Institute of Cancer Research/The Royal Marsden NHS Foundation Trust, Sutton, UK.
B
B
Basu
J
J
Vitfell-Pedersen
V
V
Moreno Garcia
M
M
Puglisi
A
A
Tjokrowidjaja
K
K
Shah
S
S
Malvankar
B
B
Anghan
J S
JS
de Bono
S B
SB
Kaye
L R
LR
Molife
U
U
Banerji
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D011379:Prognosis; D012189:Retrospective Studies; D055815:Young Adult
D000970:Antineoplastic Agents; D003404:Creatinine