Adjustment of creatinine clearance for carboplatin dosing in Calvert's formula and clinical efficacy for lung cancer

• Published in: Cancer medicine (Malden, MA) Vol. 12; no. 15; pp. 15955 - 15969
• Main Authors: Hatta, Takahiro, Hase, Tetsunari, Hara, Toru, Kimura, Tomoki, Kojima, Eiji, Abe, Takashi, Horio, Yoshitsugu, Goto, Yasuhiro, Ozawa, Naoya, Yogo, Naoyuki, Shibata, Hirofumi, Shimokata, Tomoya, Oguri, Tetsuya, Yamamoto, Masashi, Yanagisawa, Kiyoshi, Ando, Masahiko, Ando, Yuichi, Kondo, Masashi, Ishii, Makoto, Hasegawa, Yoshinori
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.08.2023; John Wiley and Sons Inc; Wiley
• Subjects: Age; Cancer therapies; Carboplatin; Chemotherapy; Clinical Cancer Research; Clinical medicine; Cockcroft–Gault formula; Creatinine; creatinine clearance; Dosage; Glomerular filtration rate; Lung Cancer; Non-small cell lung carcinoma; non‐small‐cell lung cancer; Radiation therapy; Toxicity; Translational Research; Japan; creatinine clearance; Cockcroft-Gault formula; glomerular filtration rate; carboplatin; non-small-cell lung cancer
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.6235

Background The Cockcroft–Gault formula is commonly used as a substitute for glomerular filtration rate (GFR) in Calvert's formula for carboplatin dosing, where adjusting serum creatinine measured using the enzymatic method with 0.2 mg/dL has been suggested in Japan. However, the effects of these adjustments on efficacy in patients with non‐small‐cell lung cancer remain unknown. Methods We conducted a post hoc analysis of the PREDICT1 study (CJLSG1201), a multicenter prospective observational trial of carboplatin–pemetrexed. Glomerular filtration rate values in Calvert's formula were back‐calculated from the administered dosages of carboplatin and the reported value of the target area under the curve. We estimated the serum creatinine adjustments and divided the patients into crude and adjusted groups. Results Patients in the crude group (N = 169) demonstrated similar efficacy to those in the adjusted group (N = 104) in progression‐free survival (PFS) and overall survival (OS) (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.76–1.35; p = 0.916 vs. HR, 0.87; 95% CI, 0.65–1.17; p = 0.363), with higher grade 3–4 hematologic toxicity. Among patients aged ≥75 years, the crude group (N = 47) showed superior efficacy compared with the adjusted group (N = 17) in PFS and OS (HR, 0.37; 95% CI, 0.20–0.69; p = 0.002 vs. HR, 0.43; 95% CI, 0.23–0.82; p = 0.010). Conclusions Serum creatinine adjustment may be associated with similar efficacy compared to the crude serum creatinine value. In older patients, the adjustment should be cautiously applied owing to the potential for reduced efficacy. Adjustment of serum creatinine measured using the enzymatic method with 0.2 mg/dL in creatinine clearance calculation using the Cockcroft–Gault formula is associated with similar clinical efficacy and a low incidence of toxicity compared with those of non‐adjusted values in patients with preserved renal function eligible for carboplatin–pemetrexed treatment. However, adjustments should be used with special caution in older patients owing to the potential for reduced efficacy.