Capecitabine and temozolomide: design, implementation, and preliminary outcomes from a pilot project to ensure safe prescribing of oral chemotherapy.

Without adequate safety measures, oral chemotherapy can lead to undetected dosing errors. The Mayo Clinic launched a project to ensure that all capecitabine and temozolomide prescriptions receive an independent double check.

Acute kidney injury in patients with inactive cytochrome P450 polymorphisms.

Medications are a major source of acute kidney injury, especially in critically ill patients. Medication-induced renal injury can occur through a number of mechanisms. We present two cases of acute kidney injury (AKI) where inactive cytochrome P450 (CYP) polymorphism may have played a role. The first patient developed a biopsy-proven allergic interstitial nephritis following urethrotomy. Genetic testing revealed the patient to be heterozygous for an inactivating polymorphism CYP2C9*3 and homozygous for an inactivating polymorphism CYP2D6*4. Patient had received several doses of promethazine, which is metabolized by CYP2D6*4. Another patient developed AKI on several occasions after exposure to lansoprazole and allopurinol. CYP testing revealed the patient to be homozygous for inactivating polymorphism CYP2C19*2, which is responsible for the metabolism of lansoprazole. These are the first two cases of AKI associated with non-functional polymorphisms of cytochrome P450 superfamily. While the exact mechanism has not been worked out, it introduced the possibility of a new source of kidney injury.

Acquired Fanconi syndrome after treatment with capecitabine, irinotecan, and bevacizumab.

OBJECTIVE: To describe a case of acquired Fanconi syndrome after treatment with capecitabine, irinotecan, and bevacizumab. CASE SUMMARY: A 77-year-old female with metastatic colon cancer presented with vomiting and diarrhea. The patient had been diagnosed with stage IIIC (T3, N2, M0) colon cancer 18 months earlier and was initially treated with FOLFOX6 (regimen of oxaliplatin, fluorouracil, and leucovorin) after her hemicolectomy. She was switched to a capecitabine/oxaliplatin regimen after 4 cycles due to central access problems. She did well until 10 months after her cancer diagnosis, when metastasis was discovered. She was started on reduced doses of capecitabine, irinotecan, and bevacizumab. After her eleventh cycle, she presented to the hospital with the above symptoms. Laboratory test results showed hypokalemia, hypocalcemia, hypophosphatemia, and hypouricemia. The patient had not been started on any new medications other than chemotherapy for over 1 year. The electrolyte derangements were new, since the patient had laboratory values checked every 3 weeks. Despite daily intravenous replacements, the electrolyte abnormalities persisted. Laboratory evaluations demonstrated the presence of euglycemic glucosuria and a high fractional excretion of phosphorus in the setting of hypophosphatemia. Fanconi syndrome was confirmed by demonstration of aminoaciduria. DISCUSSION: Fanconi syndrome is a disorder characterized by proximal tubular dysfunction resulting in electrolyte wasting. In the acquired form, medications and multiple myeloma are the most common causes. Based on the Naranjo probability scale, a drug was the probable cause of Fanconi syndrome in our patient. However, because multiple drugs were involved, it was not possible to determine which one was the culprit. CONCLUSIONS: This is the first case of Fanconi syndrome reported after the administration of capecitabine, irinotecan, and bevacizumab. More studies are needed to confirm this association.

Acute renal failure after treatment with sunitinib in a patient with multiple myeloma.

Sunitinib is a multiple tyrosine kinase receptors inhibitor that is approved for the treatment of advanced renal cell carcinoma. Amongst its targets are fetal liver tyrosine kinase receptor 3 (FLT 3) and vascular endothelial growth factor receptor (VEGFR). Renal toxicity has not been reported from the trials, but several patients have been reported to develop a pre-eclampsia-like syndrome. We report the first case of acute tubular necrosis in a patient with multiple myeloma following treatment with sunitinib.