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• W2000692558 abstract "Oxaliplatin is a third-generation platinum compound, which shows high activity for the treatment of advanced colon cancer, especially in various combination schedules with 5-fluorouracil [1.Haller D.G. Safety of oxaliplatin in the treatment of colorectal cancer.Oncology (Huntingt). 2000; 14: 15-20PubMed Google Scholar]. It is also undergoing some adjuvant trials.Oxaliplatin has shown a good safety profile in all previous reports. The recommended dose is 85 mg/m2 every 2 weeks or130 mg/m2 every 3 weeks [1.Haller D.G. Safety of oxaliplatin in the treatment of colorectal cancer.Oncology (Huntingt). 2000; 14: 15-20PubMed Google Scholar, 2.Cvitkovic E. Bekradda M. Oxaliplatin: a new therapeutic option in colorectal cancer.Semin Oncol. 1999; 26: 647-662PubMed Google Scholar]. The most common toxicity is cumulative peripheral sensory neurotoxicity characterized by paresthesia and dysesthesia that are induced or exacerbated by exposure to cold [2.Cvitkovic E. Bekradda M. Oxaliplatin: a new therapeutic option in colorectal cancer.Semin Oncol. 1999; 26: 647-662PubMed Google Scholar, 3.Extra J.-M. Marty M. Brienza S. Misset J.-L. Pharmacokinetics and safety profile of oxaliplatin.Semin Oncol. 1998; 25: 13-22PubMed Google Scholar]. Nausea/vomiting occurs with high frequency; mild hematologic toxicity is sporadic [2.Cvitkovic E. Bekradda M. Oxaliplatin: a new therapeutic option in colorectal cancer.Semin Oncol. 1999; 26: 647-662PubMed Google Scholar]. Unlike other platinum derivatives, no ototoxicity or nephrotoxicity have been reported [1.Haller D.G. Safety of oxaliplatin in the treatment of colorectal cancer.Oncology (Huntingt). 2000; 14: 15-20PubMed Google Scholar, 2.Cvitkovic E. Bekradda M. Oxaliplatin: a new therapeutic option in colorectal cancer.Semin Oncol. 1999; 26: 647-662PubMed Google Scholar]. WHO grade 2 transient serum creatinine elevation was described in a phase I study in 4% of cycles [3.Extra J.-M. Marty M. Brienza S. Misset J.-L. Pharmacokinetics and safety profile of oxaliplatin.Semin Oncol. 1998; 25: 13-22PubMed Google Scholar].When adding oxaliplatin to fluorouracil/leucovorin-based regimens, a higher incidence of diarrhea, stomatitis and grade 3–4 neutropenia may occur; in contrast, hepatic or renal toxicities do not increase [1.Haller D.G. Safety of oxaliplatin in the treatment of colorectal cancer.Oncology (Huntingt). 2000; 14: 15-20PubMed Google Scholar]. Severe dehydration due to diarrhea during polychemotherapeutic regimens with fluorouracil should be considered an important cause of renal failure.This is a case of a 57-year-old man, who experienced a life-threatening acute tubular necrosis, probably due to oxaliplatin. He received the diagnosis of poorly differentiated adenocarcinoma of the colon with synchronous liver metastases in 1998. He was treated with several chemotherapy regimens for ~4 years, including 16 cycles of De Gramont plus oxaliplatin (85 mg/m2 every 2 weeks) from February 2000 to October 2000. A reduction of the oxaliplatin dose to 50% was required because of paresthesia.In November 2001, due to disease progression, another attempt with oxaliplatin was made, according to the following 28-day schedule: oxaliplatin 85 mg/m2 2-h infusion on days 1 and 15; folinic acid 10 mg/m2 2-h infusion on days 1, 8 and 15; 5-fluorouracil 500 mg/m2 as a bolus on days 1, 8 and 15. Oxaliplatin was given at a reduced dosage of 75%. During the third infusion of oxaliplatin, he experienced abdominal pain and fever (∼39°C). After a few hours, an episode of gross hematuria occurred. One week later, the patient was admitted to hospital for severe asthenia, somnolence and oliguria; serum creatinine was 7.3 mg/dl and azotemia was 250 mg/dl. He was treated with diuretics and monitored daily for fluid balance. Pre- and post-renal causes of renal failure were excluded. Therefore, a renal biopsy was performed, revealing disrupted, necrotic and regenerating tubular epithelium, intratubular casts, and interstitial cellular infiltration. According to this description an acute tubular necrosis with suspected toxic damage was diagnosed. Renal function completely recovered after 3 months.We believe that this is the first report of an unexpected acute nephrotoxicity due to oxaliplatin, not correlated to dehydration but to direct damage of the kidney with acute tubular necrosis. The patient had previously received oxaliplatin without any renal consequence. We propose that the renal damage could have been caused by the cumulative dose of oxaliplatin. The association of oxaliplatin with the bolus infusion of5-fluorouracil rather than the continuous infusion might also have been determinant. Oxaliplatin is a third-generation platinum compound, which shows high activity for the treatment of advanced colon cancer, especially in various combination schedules with 5-fluorouracil [1.Haller D.G. Safety of oxaliplatin in the treatment of colorectal cancer.Oncology (Huntingt). 2000; 14: 15-20PubMed Google Scholar]. It is also undergoing some adjuvant trials. Oxaliplatin has shown a good safety profile in all previous reports. The recommended dose is 85 mg/m2 every 2 weeks or130 mg/m2 every 3 weeks [1.Haller D.G. Safety of oxaliplatin in the treatment of colorectal cancer.Oncology (Huntingt). 2000; 14: 15-20PubMed Google Scholar, 2.Cvitkovic E. Bekradda M. Oxaliplatin: a new therapeutic option in colorectal cancer.Semin Oncol. 1999; 26: 647-662PubMed Google Scholar]. The most common toxicity is cumulative peripheral sensory neurotoxicity characterized by paresthesia and dysesthesia that are induced or exacerbated by exposure to cold [2.Cvitkovic E. Bekradda M. Oxaliplatin: a new therapeutic option in colorectal cancer.Semin Oncol. 1999; 26: 647-662PubMed Google Scholar, 3.Extra J.-M. Marty M. Brienza S. Misset J.-L. Pharmacokinetics and safety profile of oxaliplatin.Semin Oncol. 1998; 25: 13-22PubMed Google Scholar]. Nausea/vomiting occurs with high frequency; mild hematologic toxicity is sporadic [2.Cvitkovic E. Bekradda M. Oxaliplatin: a new therapeutic option in colorectal cancer.Semin Oncol. 1999; 26: 647-662PubMed Google Scholar]. Unlike other platinum derivatives, no ototoxicity or nephrotoxicity have been reported [1.Haller D.G. Safety of oxaliplatin in the treatment of colorectal cancer.Oncology (Huntingt). 2000; 14: 15-20PubMed Google Scholar, 2.Cvitkovic E. Bekradda M. Oxaliplatin: a new therapeutic option in colorectal cancer.Semin Oncol. 1999; 26: 647-662PubMed Google Scholar]. WHO grade 2 transient serum creatinine elevation was described in a phase I study in 4% of cycles [3.Extra J.-M. Marty M. Brienza S. Misset J.-L. Pharmacokinetics and safety profile of oxaliplatin.Semin Oncol. 1998; 25: 13-22PubMed Google Scholar]. When adding oxaliplatin to fluorouracil/leucovorin-based regimens, a higher incidence of diarrhea, stomatitis and grade 3–4 neutropenia may occur; in contrast, hepatic or renal toxicities do not increase [1.Haller D.G. Safety of oxaliplatin in the treatment of colorectal cancer.Oncology (Huntingt). 2000; 14: 15-20PubMed Google Scholar]. Severe dehydration due to diarrhea during polychemotherapeutic regimens with fluorouracil should be considered an important cause of renal failure. This is a case of a 57-year-old man, who experienced a life-threatening acute tubular necrosis, probably due to oxaliplatin. He received the diagnosis of poorly differentiated adenocarcinoma of the colon with synchronous liver metastases in 1998. He was treated with several chemotherapy regimens for ~4 years, including 16 cycles of De Gramont plus oxaliplatin (85 mg/m2 every 2 weeks) from February 2000 to October 2000. A reduction of the oxaliplatin dose to 50% was required because of paresthesia. In November 2001, due to disease progression, another attempt with oxaliplatin was made, according to the following 28-day schedule: oxaliplatin 85 mg/m2 2-h infusion on days 1 and 15; folinic acid 10 mg/m2 2-h infusion on days 1, 8 and 15; 5-fluorouracil 500 mg/m2 as a bolus on days 1, 8 and 15. Oxaliplatin was given at a reduced dosage of 75%. During the third infusion of oxaliplatin, he experienced abdominal pain and fever (∼39°C). After a few hours, an episode of gross hematuria occurred. One week later, the patient was admitted to hospital for severe asthenia, somnolence and oliguria; serum creatinine was 7.3 mg/dl and azotemia was 250 mg/dl. He was treated with diuretics and monitored daily for fluid balance. Pre- and post-renal causes of renal failure were excluded. Therefore, a renal biopsy was performed, revealing disrupted, necrotic and regenerating tubular epithelium, intratubular casts, and interstitial cellular infiltration. According to this description an acute tubular necrosis with suspected toxic damage was diagnosed. Renal function completely recovered after 3 months. We believe that this is the first report of an unexpected acute nephrotoxicity due to oxaliplatin, not correlated to dehydration but to direct damage of the kidney with acute tubular necrosis. The patient had previously received oxaliplatin without any renal consequence. We propose that the renal damage could have been caused by the cumulative dose of oxaliplatin. The association of oxaliplatin with the bolus infusion of5-fluorouracil rather than the continuous infusion might also have been determinant." @default.
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• W2000692558 title "A case of acute tubular necrosis due to oxaliplatin" @default.
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