Carboplatin dose based on actual renal function: no excess of acute haematotoxicity in adjuvant treatment in seminoma stage I

Abstract

IntroductionThe practice of carboplatin dosing is not concordant among different centres and oncologists. Some clinical guidelines recommend capping of the carboplatin dose at, for example, creatinine-clearance (Crea-Cl) of 125 mL/min because of concerns of excessive toxicity. Clinical data to support such recommendations are lacking, especially in patients with seminoma.MethodsThis is a retrospective analysis of acute haematotoxicity of patients with stage I seminoma treated with adjuvant carboplatin area under the curve (AUC) 7 in routine practice in two Swiss centres in 2005–2015, and a comparison of incidence and grade (according to Common Terminology Criteria for Adverse Events v4.0) of haematological adverse events (hAEs) in patients with Crea-Cl <125 mL/min vs >125 mL/min without dose capping.Results74 patients with 229 documented measurements were included (median 3/patient). A total of 151 hAEs occurred. Platelet nadir occurred earlier than median white cell/neutrophil count (median day 15 vs day 22; P<0.0001). The majority of hAEs were mild, with more than 80% being of grade 1. Only two (2.7%) clinically relevant hAEs necessitating subsequent interventions occurred (one patient received platelet transfusion, one patient with febrile neutropaenia). Haematological toxicities were not statistically different in patients dosed with Crea-Cl >125 mL/min versus those with Crea-Cl <125 mL/min. No hAEs other than grade 1 occurred before day 10 and after day 24.ConclusionsToxicity after single-dose carboplatin AUC 7 is generally mild. No excess of toxicity occurs in patients with high Crea-Cl above 125 mL/min, and therefore dose capping is not routinely necessary. In addition, this study provides a rationale for efficient use of healthcare services without compromising patients’ safety.

Phase 1 study of veliparib (ABT-888), a poly (ADP-ribose) polymerase inhibitor, with carboplatin and paclitaxel in advanced solid malignancies

“…The value from the Cockcroft-Gault formula is then imputed into the Calvert equation, which is derived in 31 mostly female patients with an R 2 of 0.76 to calculate a carboplatin dose [41]. The calculated dose may be capped by the truncation of the glomerular filtration rate value at 125 mL/min [42], which is incorrectly assumed to be the physiological maximum [43].…”

Evaluation of the pharmacokinetic drug-drug interaction potential of iohexol, a renal filtration marker

“…The value for creatinine clearance is then imputed into the Calvert equation, which is also biased, having been derived in only 31 mostly female patients with an R 2 of 0.76 [3]. The calculated dose may be capped by the truncation of GFR at 125 mL/min [12] (incorrectly assumed to be the physiological maximum [13]), or setting a lower limit value for SCr. It is therefore not a surprise that we do not accurately and precisely achieve the target AUC.…”

Management of acute kidney injury in gastrointestinal tumor: An overview

“…However, nephrotoxicity can be considered the result of oxaliplatin in cases of repeated exposure[ 52 ]. Carboplatin is known for its low nephrotoxicity, but only case reports have confirmed that carboplatin can cause biopsy-proven AIN[ 51 , 53 , 54 ].…”