Comparison of Myelotoxicity and Nephrotoxicity Between Daily Low-Dose Cisplatin With Concurrent Radiation and Cyclic High-Dose Cisplatin in Non-Small Cell Lung Cancer Patients

Abstract

Aim Antineoplastic effect of cisplatin, the first line treatment in non-small cell lung cancer (NSCLC), is hindered by its nephrotoxicity and myelotoxicity. Both low-dose and high-dose regimens are used in the management of NSCLC. The aim of this study is to assess the risk on myelotoxicity and nephrotoxicity from the daily low-dose cisplatin (DLD) treatment as compared to cyclic high-dose cisplatin (CHD). Methods A retrospective cohort study was conducted. NSCLC patients treated with cisplatin between 2011 and 2018 in the Amsterdam UMC or Antoni van Leeuwenhoek cancer hospital were studied. Myelotoxicity and nephrotoxicity were defined based on common terminology criteria (CTCAE v4.03) and categorized as ≥grade 1 and ≥grade 2. Modified Poisson regression and Cox proportional hazards model were used to estimate relative risks and cumulative hazard respectively. Results Of the 115 NSCLC patients receiving DLD (N=62) and CHD (N=53), 60% had ≥grade 1 anemia, 33.9% leukopenia, 31.3% neutropenia, 27.8% thrombocytopenia, 32.2% acute nephrotoxicity with combined definition (Cr-electrolyte nephrotoxicity), and 58.3% chronic nephrotoxicity. The DLD group was older, had an earlier cancer stage, had more comorbidities, and had higher baseline albumin levels. In the DLD group less ≥grade 2 toxicities were reported compared to the CHD group except for Cr-electrolyte nephrotoxicity. However, there was a stronger association in the DLD group with ≥grade 1 leukopenia, thrombocytopenia, and Cr-electrolyte nephrotoxicity. The DLD group developed significantly more ≥grade 1 leukopenia [adjusted relative risk (adjRR)=1.83, 95% CI 1.02–3.27], thrombocytopenia (adjRR=3.43, 95% CI 1.64–7.15), and ≥grade 2 Cr-electrolyte nephrotoxicity (adjRR=3.02, 95% CI 1.20–7.56). The DLD group had a lower adjusted cumulative hazard for developing ≥grade 2 myelotoxicity and chronic nephrotoxicity but not for Cr-electrolyte nephrotoxicity [adjusted hazard ratio (adjHR)=3.90, 95% CI 1.35–11.23]. In contrast, DLD showed protective effect to ≥grade 2 nephrotoxicity when definition was restricted to the traditional creatinine-based definition (adjRR=0.07, 95% CI 0.01–0.86; adjHR=0.05, 95% CI 0.01–0.56). Conclusions Overall, the DLD regimen was safer than the CHD regimen when assessing the risk of ≥grade 2 myelotoxicity and nephrotoxicity. However, this might not be the case in patients with a higher risk of electrolyte abnormalities.

Prediction model of acute kidney injury induced by cisplatin in older adults using a machine learning algorithm

“…In addition, cisplatin daily dose is associated with increased toxicity in all age groups. Daily low-dose cisplatin treatment decreases the risk of nephrotoxicity better than cyclic high-dose cisplatin treatment [ 28 ]. Our result agrees with those of a previous report and suggests that daily dose reduction of cisplatin decreases the risk of Cis-AKI.…”

Toxicity of pemetrexed during renal impairment explained—Implications for safe treatment

“…Although this enabled an unclouded assessment of the neutropenic effects of pemetrexed, it should be noted that pemetrexed is often combined with these drugs. As these platinum‐based anticancer agents may also cause myelotoxicity it is likely that the probability of toxicity in combination with these drugs is even higher 28 …”

“…As these platinumbased anticancer agents may also cause myelotoxicity it is likely that the probability of toxicity in combination with these drugs is even higher. 28 Since we now know that potentially subtherapeutic pemetrexed doses in patients with renal impairment can still result in severe neutropenia, we strongly recommend against administration of pemetrexed in this patient group. A pemetrexed dose leading to an equivalent neutropenic response in patients with renal dysfunction is considerably lower and leads to a substantial (13-fold) lower AUC than after a pemetrexed dose of 500 mg/m 2 for a patient with adequate renal function.…”