Renal damage induced by pemetrexed causing drug discontinuation: a case report and review of the literature

Sbitti, Yassir; Chahdi, Hafsa; Slimani, Khaoula; Debbagh, Adil; Mokhlis, Anouar; Albouzidi, A.; Bennani, Fahd; Errihani, Hassan; Ichou, Mohamed

doi:10.1186/s13256-017-1348-6

Cited by 7 publications

(8 citation statements)

References 14 publications

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“…In addition, the OS results in this study could not be compared to the efficacy of secondary treatments between the two groups. However, previous studies on kidney damage have reported acute kidney damage primarily due to tubular cell injury [9,19,20], or increased blood concentration and intense side effects in cases of decreased kidney function as PEM is excreted by the kidneys [6,21]. To the best of our knowledge, the findings of this study are the first to confirm chronic renal dysfunction due to long-term PEM exposure.…”

Section: Discussionmentioning

confidence: 48%

Long-term exposure to pemetrexed induces chronic renal dysfunction in patients with advanced and recurrent non-squamous cell lung cancer: a retrospective study

et al. 2020

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Background Pemetrexed (PEM) is administered over a long term to patients with non-squamous cell lung cancer as a maintenance therapy after platinum combination induction chemotherapy. Although decreased renal function owing to long-term PEM exposure has been reported, changes in the renal function of individual patients have not been reported. This study aimed to evaluate serum creatinine (Scr) in individual patients over time and determine whether long-term PEM exposure contributed to increased Scr. Methods A retrospective study was performed using 90 non-squamous cell lung cancer patients, who had received maintenance therapy with PEM ± bevacizumab (BEV) after carboplatin + PEM ± BEV therapy at the Sapporo Minami-Sanjo Hospital from February 2012 to February 2019. Using Scr at the start of induction chemotherapy as the baseline, we calculated the correlation coefficient (r) of the rate of Scr change in an individual patient and the number of treatment courses to divide patients into two groups for comparison: patients with + 0.4 < r ≦ + 1.0 and an observed positive correlation (the r+0.4< group), and patients with − 1.0 ≦ r ≦ + 0.4 and no observed positive correlation (the r+0.4≧ group). Results Statistically significant differences between the r+0.4< group and the r+0.4≧ group were observed for the following parameters: the median cumulative dose of PEM (interquartile range) [9100 (6365, 12,260) mg/body vs. 5600 (4140, 7440) mg/body, P < 0.01]; the number of patients taking nonsteroidal anti-inflammatory drugs at the start of treatment [15 patients (31%) vs. 3 patients (7%), P < 0.01]; and the median number of treatment courses starting from induction chemotherapy [11 (8, 14) courses vs. 8 (6, 11) courses, P < 0.01]. Next, the results of univariate and multivariate analyses demonstrated that the cumulative dose of PEM (≧ 7000 mg/body vs < 7000 mg/body, OR 2.40; 95% CI, 1.22–4.75, P = 0.01) was an independent explanatory variable of the r+0.4< group. Conclusions Long-term PEM exposure may induce chronic renal dysfunction. Hence, maintaining kidney function during PEM treatment by reducing the use of combination drugs and the risk of other renal dysfunctions, such as dehydration, may help patients continue therapy and contribute to their long-term survival.

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Section: Discussionmentioning

confidence: 48%

Long-term exposure to pemetrexed induces chronic renal dysfunction in patients with advanced and recurrent non-squamous cell lung cancer: a retrospective study

et al. 2020

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“…The recommended dosage is 500 mg/m 2 intravenous once every 21 days as a single agent or in combination with cisplatin. 8 The substance is not significantly metabolised. Since approximately 80% of it is fully removed unchanged by the renal emunctory, it is contraindicated if creatinine clearance is less than 45 ml/minute.…”

Section: Discussionmentioning

confidence: 99%

“…Only after the fourth cycle was administered, and in the absence of all other potentially nephrotoxic agents, did the patients undergo renal failure. 8 Although several AKI risk factors were present (dehydration, NSAID use, and radiocontrast agents), none of them appeared to be the cause of kidney injury. However, we can't rule out the possibility that these variables play a role.…”

Section: Discussionmentioning

confidence: 99%

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A retrospective study on pemetrexed induced nephrotoxicity in non-small cell lung carcinoma patients

Reddy¹,

Punukula²,

Bhavya³

et al. 2021

Int J Basic Clin Pharmacol

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Background: Pemetrexed (PEM) is a new-generation multitargeted antifolate agent that has been shown to have broad-spectrum efficacy in a variety of human cancers, including NSCLC and mesothelioma. Dose-limiting hematologic toxicities are among the most serious side effects. PEM nephrotoxicity is well-known, but its occurrence is thought to be rare. Aim was to determine nephrotoxicity induced due to pemetrexed in non-small cell lung cancer patients.Methods: In patients with the NSCLC, we record a retrospective review on PEM- induced renal toxicity. A total of 327 NSCLC patients were treated in our hospital between 2012 and 2019. Of these, 134 patients were diagnosed with 2 or more chemotherapy cycles. 60 of these patients have been diagnosed with combination of antineoplastic drugs based on pemetrexed and platinum. Others were removed from the study and were also required to be tested for other potential causes of renal injury.Results: Suitable statistical tools were used and data was analysed which showed that repeated chemo cycles of pemetrexed leads to the reversible acute kidney injury. With the results from our study we can understand the severity of nephrotoxicity induced with pemetrexed in patients with non-small cell lung cancer. Most of the patients were in the first and second stages of nephrotoxicity and most of them were male. Majority of the patients were also above 40 years of age and also endured more than 4 chemo cycles.Conclusions: It shows that PEM allows longer survival, but acute or chronic kidney failure is the price for this achievement. In conclusion, renal toxicity should be controlled routinely in patients treated with pemetrexed. Before each cycle of pemetrexed, creatinine clearance should be measured. Patients need to be well hydrated during treatment. The patient should also be tested for concomitant medications, and any nephrotoxic symptoms should be reviewed and those drugs removed.

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“…The decline in renal function can occur as a direct toxic effect of the chemotherapeutic agent, but also patient-related and other drug-related factors play pivotal roles [4]. Nephrotoxicity often is a reason of treatment discontinuation or dose reduction resulting in a suboptimal treatment schedule [5]. The fact that about 60% of the people with cancer have underlying compromised renal function stresses the importance of this topic [6].…”

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confidence: 99%

Optimisation of chemotherapy in the era of immunotherapy

Boosman

Burgers

2018

Eur Respir J

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]. Even in the era of immunotherapy and personalised medicine, chemotherapy remains a cornerstone in the treatment of nonsmall cell lung cancer (NSCLC) [1]. Chemotherapy improves the length and quality of life of patients with metastatic disease for tumours both with and without oncogenic drivers. Chemotherapy in combination with checkpoint inhibitors is about to become the most effective first-line therapy for NSCLC [2]. Also in the adjuvant setting, i.e. adding chemotherapy after surgery, chemotherapy improves survival with an absolute increase of 4% at 5 years [3].

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Renal damage induced by pemetrexed causing drug discontinuation: a case report and review of the literature

Cited by 7 publications

References 14 publications

Long-term exposure to pemetrexed induces chronic renal dysfunction in patients with advanced and recurrent non-squamous cell lung cancer: a retrospective study

Long-term exposure to pemetrexed induces chronic renal dysfunction in patients with advanced and recurrent non-squamous cell lung cancer: a retrospective study

A retrospective study on pemetrexed induced nephrotoxicity in non-small cell lung carcinoma patients

Optimisation of chemotherapy in the era of immunotherapy

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