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Evaluating dose of cisplatin responsible for causing nephrotoxicity.

ABSTRACT: Nephrotoxicity is a well-known side effect of cisplatin for cancer treatment. Various regimens have been developed to treat cancer based on the type and severity of the tumor. We focus on the docetaxel, cisplatin, and 5-fluorouracil regimen, which is called the TPF regimen, where the standard dose of cisplatin is 60 mg/m2. The aim of this study is to examine the relationship of the dosage of cisplatin that causes nephrotoxicity and back ground factors of patients using information about the dose of cisplatin actually administered to patients. It is shown that nephrotoxicity may be caused by a substantially smaller dosage than the standard dose of cisplatin in the TPF regimen, indicating the need for dose adjustment, taking into account the patient's background factors in the treatment of a cancer.

SUBMITTER: Higuchi K

PROVIDER: S-EPMC6483206 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Evaluating dose of cisplatin responsible for causing nephrotoxicity.

Higuchi Kyouko K Yanagawa Takashi T

PloS one 20190425 4

Nephrotoxicity is a well-known side effect of cisplatin for cancer treatment. Various regimens have been developed to treat cancer based on the type and severity of the tumor. We focus on the docetaxel, cisplatin, and 5-fluorouracil regimen, which is called the TPF regimen, where the standard dose of cisplatin is 60 mg/m2. The aim of this study is to examine the relationship of the dosage of cisplatin that causes nephrotoxicity and back ground factors of patients using information about the dose ...[more]

PMID: 31022233

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Project description: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.

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Evaluating dose of cisplatin responsible for causing nephrotoxicity.

Publications

Evaluating dose of cisplatin responsible for causing nephrotoxicity.

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