Renal toxicity of Oxaliplatin

Labaye, Jacques; Sarret, Damien; Duvic, C.; Herody, M.; Didelot, F.; Nédélec, G; Nôël, Laure-Hélène

doi:10.1093/ndt/gfh826

Cited by 47 publications

(42 citation statements)

References 4 publications

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“…Excluding the present case, seven cases of AKI have been reported after treatment with oxaliplatin (Table 4) since 1999, when the first case of hemolytic anemia with AKI was reported by Desrame et al [6][7][8][9][10][11][12]. All cases were accompanied by anemia and four cases were identified as immune-related hemolytic anemia with positive results for DAT [6,8,11,12].…”

Section: Discussionmentioning

confidence: 71%

“…Lee et al [5] reported that the important grade 3-4 toxicities were neutropenia (34.1 %), leukopenia (7.3 %), nausea (9.8 %), and vomiting (7.3 %). Hemolysis and renal toxicity related to oxaliplatin are quite rare, reported in only a few cases [6][7][8][9][10][11][12]. Cases with acute renal injury have been reported in only seven patients to date.…”

Section: Introductionmentioning

confidence: 99%

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A rare case of acute kidney injury associated with autoimmune hemolytic anemia and thrombocytopenia after long-term usage of oxaliplatin

Ito

Mizuno

et al. 2012

Clin Exp Nephrol

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Oxaliplatin is effective in advanced colorectal cancer and is known to have relatively few side effects, such as hemolysis and renal toxicity. We report a case of acute kidney injury (AKI) after treatment with a combination of oxaliplatin, folinic acid and 5-fluorouracil or capecitabine. The patient developed acute renal failure, hemolytic anemia and thrombocytopenia after the 34th course of chemotherapy including oxaliplatin. A positive direct antiglobulin test and detection of immunoglobulin G and complement C3b and C3d on erythrocytes suggested the diagnosis of immune-related severe intravascular hemolytic anemia. She was successfully treated and recovered using plasma exchange, corticosteroids and hemodialysis therapy. Only seven other cases of AKI associated with oxaliplatin use have been reported to date. As in this case, acute hemolysis due to autoimmune mechanisms and subsequent AKI occurred suddenly after frequent use of oxaliplatin in four of those cases. We should be aware that oxaliplatin may cause sudden life-threatening hemolysis by drug-induced antibodies and subsequent AKI, even though oxaliplatin is frequently administered without side effects. This represents the first case report of AKI-related hemolysis due to oxaliplatin in Japan.

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

A rare case of acute kidney injury associated with autoimmune hemolytic anemia and thrombocytopenia after long-term usage of oxaliplatin

Ito

Mizuno

et al. 2012

Clin Exp Nephrol

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“…Nonetheless, there were two case reports on oxaliplatin-related severe renal toxicity [24,25] : oxaliplatin induced acute tubular necrosis, and a relationship between the cumulative dose of oxaliplatin and the grade of toxicity was suggested. In several phase II trials evaluating oxaliplatin combinations in the 370 study patients, only 1 patient with elevated serum creatinine 6 grade 3 was reported, who manifested acute renal failure after 17 cycles and required transient hemodialysis [9, 12-14, 18, 25] .…”

Section: Discussionmentioning

confidence: 99%

Oxaliplatin Combined with Continuous Infusion of 5-Fluorouracil as First-Line Chemotherapy in Patients with Metastatic or Recurrent Gastric Adenocarcinoma

Lim¹,

Cho²,

Oh³

et al. 2009

Chemotherapy

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Background: The aim of this clinical study was to evaluate the efficacy of combination chemotherapy of oxaliplatin, leucovorin and continuous-infusion 5-fluorouracil (5-FU) for advanced gastric cancer. Methods: Patients with previously untreated gastric cancer with measurable disease received oxaliplatin (100 mg/m², day 1), followed by leucovorin (100 mg/m², day 1) and 5-FU (2,400 mg/m², days 1–2), which was repeated every 2 weeks. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicity. Results: Forty-eight patients were enrolled, and 45 were evaluable for response. A total of 320 cycles of chemotherapy were administered (median 6 cycles per patient). One complete response (2.1%) and 19 partial responses (39.6%) were noted, resulting in an ORR of 41.7% (95% confidence interval, CI: 27.7–55.6%) by intent-to-treat analysis. With a median follow-up duration of 22 months, the median PFS was 5.3 (95% CI: 2.8–7.8) months and the median OS was 13.6 (95% CI: 9.3–17.9) months. There was 1 treatment-related death, and the most common grade 3/4 toxicity was neutropenia (36.1%). Three patients discontinued treatment because of serum creatinine elevation. Conclusion: This study reaffirms the efficacy of oxaliplatin in advanced gastric cancer, but its dose of 100 mg/m² remains to be reconsidered in Korean patients.

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“…On the other hand, the effects of nedaplatin and oxaliplatin on LDH release, DNA fragmentation and caspase activation were comparable, although the cellular accumulation ( fig. 1 ) and adverse effects in clinical studies [27,28] differed between these drugs. In addition, carboplatin showed the least activity in terms of LDH release, DNA fragmentation and caspase activation, and also less accumulation.…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Cell Injury after Exposure to Antitumor Platinum Derivatives in Kidney Tubular Epithelial Cells

Kitada

Takara²,

Itoh³

et al. 2008

Chemotherapy

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Background: Platinum derivatives differ in effectiveness and safety. The purpose of this study is to compare differences in the mechanism of nephrotoxicity among these derivatives. Methods: LLC-PK₁ cells were used as a model of tubular epithelial cells. Cytotoxicity was evaluated by WST-1 assay, and cellular accumulation of platinum was examined by inductively coupled plasma mass spectrometer. As indexes of necrosis and apoptosis, lactate dehydrogenase release, DNA fragmentation and caspase 3 activation were examined. Results: In terms of cytotoxicity, the derivatives ranked in the order of oxaliplatin > cisplatin > nedaplatin > carboplatin, being comparable with that for the level of platinum accumulated in LLC-PK₁ cells. Lactate dehydrogenase release and DNA fragmentation were observed following treatment with all the derivatives, but were lowest for carboplatin. In terms of activating caspase 3, the order was cisplatin > nedaplatin > oxaliplatin > carboplatin. Conclusion: Cytotoxicity by the derivatives was dependent on cellular accumulation of platinum and suggested to be mediated by apoptosis and necrosis; however, contributions differed among the derivatives.

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Renal toxicity of Oxaliplatin

Cited by 47 publications

References 4 publications

A rare case of acute kidney injury associated with autoimmune hemolytic anemia and thrombocytopenia after long-term usage of oxaliplatin

A rare case of acute kidney injury associated with autoimmune hemolytic anemia and thrombocytopenia after long-term usage of oxaliplatin

Oxaliplatin Combined with Continuous Infusion of 5-Fluorouracil as First-Line Chemotherapy in Patients with Metastatic or Recurrent Gastric Adenocarcinoma

Comparative Analysis of Cell Injury after Exposure to Antitumor Platinum Derivatives in Kidney Tubular Epithelial Cells

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