levoleucovorin and Hyperammonemia

A 60-year-old woman was administered mFOLFOX6 therapy as postoperative adjuvant chemotherapy for fStage III a ascending colon cancer. The patient developed a disorder of consciousness(Japan Coma Scale[JCS]III-200)immediately after the completion of the therapy. Blood ammonia levels were high at 319 mg/dL, and a diagnosis of disturbance of consciousness due to hyperammonemia was made. The patient's state of consciousness improved on the following day as blood ammonia levels decreased due to treatment with branched chain amino acid(BCAA)formulation and oxygen. Two months later, mFOLFOX6 therapy was again administered with strengthening measures for side effects to nausea and vomiting and reducing 5-FU, but the patient again developed a disorder of consciousness(JCS III-200). The 5-FU administration rate was considered as a potential cause of hyperammonemia. Hyperammonemia induced by 5-FU is relatively rare, with a reported incidence of 5-9%; however, caution is required with high dosage regimens of 5-FU that are currently recommended for colorectal cancer therapy because hyperammonemia is an important side effect.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Diseases; Chemotherapy, Adjuvant; Colon, Ascending; Colonic Neoplasms; Female; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Middle Aged; Organoplatinum Compounds

A 79-year-old woman with colon cancer and multiple liver metastases was admitted to our hospital for systemic chemotherapy. She underwent first cycle of modified FOLFOX6 chemotherapy. She was confused on treatment day 5. Blood test revealed her serum ammonia level to be 121 microg/dl. We diagnosed 5-fluorouracil (5FU)-induced hyperammonemia. Conservative treatment resulted in improvement of metal status. The reason for hyperammonemia after administration of 5FU was the excess production of ammonium from metabolites of 5FU.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Liver Neoplasms; Organoplatinum Compounds

FOLFOX is a standard chemotherapy regimen used to treat colorectal cancer. Adverse events associated with FOLFOX treatment include peripheral neuropathy and myelosuppression. This report discusses the case of a 64-year-old man with rectal cancer who developed hyperammonemia and impaired consciousness following initiation of mFOLFOX6 as a postoperative adjuvant therapy.. This case study reports on the clinical disease progression of the aforementioned patient.. Although impaired consciousness is a rare adverse reaction of FOLFOX, it has a major psychological impact on the patient and his/her family. Hyperammonemia should therefore be considered a potential cause of impaired consciousness during FOLFOX therapy and should be appropriately diagnosed and treated.

Topics: Antineoplastic Combined Chemotherapy Protocols; Consciousness; Female; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Rectal Neoplasms

A 66-year-old woman was diagnosed with stage IVb sigmoid colon cancer. Modified FOLFOX-6 (mFOLFOX-6; levofolinate‒fluorouracil‒oxaliplatin) plus panitumumab was selected as the chemotherapeutic regimen, but she was administered a regimen without oxaliplatin (L-OHP) or bolus 5-fluorouracil (5-FU) because of her general condition and concern about adverse effects. The patient had impaired consciousness on day 3 of chemotherapy. Computed tomography (CT) and magnetic resonance imaging (MRI) of the brain showed no findings of hemorrhage, infarction, brain metastasis, and leukoencephalopathy. Except for high blood ammonia concentration (353 µg/dL), there were no other findings that could have caused her condition. Impaired consciousness due to hyperammonemia was diagnosed. We started an intravenous drip supplemented with branched chain amino acids for liver protection. Approximately 6 hours later, blood ammonia level improved to 88 µg/dL, which approached the reference value. Consciousness level improved over time, reaching a level of alertness on day 5 after starting chemotherapy. 5-FU was suspected to be the cause of impaired consciousness due to hyperammonemia, but the exact cause could not be identified because most of the previously reported cases were given L-OHP, bolus 5-FU, and other concomitant medications. In this case, since there were no other concomitant medications, it is highly probable that continuous infusion of 5-FU alone caused impaired consciousness due to hyperammonemia. This is an important case that indicates the need to monitor carefully for the occurrence of hyperammonemia when 5-FU is administered continuously; it also proposes future issues for investigation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Consciousness; Female; Fluorouracil; Humans; Hyperammonemia; Leucovorin

A 76-year-old woman had underwent 5-fluorouracil(5-FU), oxaliplatin(L-OHP)combination therapy(mFOLFOX6)as first-line chemotherapy for peritoneal recurrence after resection of sigmoid colon cancer. She showed severe general fatigue and disturbance of consciousness on the second day of the 12th course of chemotherapy. Computed tomography of the head detected no abnormal findings in the central nervous system. The laboratory results revealed a marked hyperammonemia. She was diagnosed as a disturbance of consciousness due to hyperammonemia and treated her with branched- chain amino acid solution. Then the disturbance of consciousness resolved on the following day. After changing the regimen of chemotherapy, the disturbance of consciousness was not found. Recently, it has been reported that high-dose 5-FU regimen such as mFOLFOX6 causes hyperammonemia as a rare adverse event. We should take hyperammonemia into account when disturbance of consciousness occurs during high-dose 5-FU chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Consciousness; Female; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Neoplasm Recurrence, Local; Sigmoid Neoplasms

We report a case of altered consciousness related to hyperammonemia due to FOLFIRI plus bevacizumab therapy in a patient with recurrent colorectal cancer and renal dysfunction.A 76-year-old man received third-line chemotherapy for left mediastinal lymph node metastasis.He complained of diarrhea on the evening of the same day, and mental confusion on day 3 of the first FOLFIRI therapy.He had a JCS of Ⅲ(200).The laboratory results revealed a marked hyperammonemia.5 - fluorouracil(5-FU)-induced hyperammonemia was diagnosed and the patient was ventilated and managed with branchedchain amino acid solutions, lactulose, and hemodialysis in the ICU.After hemodialysis, the blood ammonia level reduced to the normal limits, and the symptoms of encephalopathy resolved on the following day.He was discharged home on the 19th day of hospitalization.5 -FU-containing therapy should be carefully administered in patients with renal dysfunction.Herein, we report a case of 5-FU-induced hyperammonemia with literature considerations.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Consciousness; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Male; Neoplasm Recurrence, Local

For several decades, 5-Fluorouracil (5-FU) has been the backbone of many chemotherapy regimens for various tumor types. Its most common side effects are gastrointestinal disorders, mucositis, myelosuppression, hand-foot syndrome, and rarely cardiac toxicity. More rarely, 5-FU infusion can induce hyperammonemic encephalopathy. 5-FU toxicities can be worsened by complete or partial genetic and/or phenotypic dihydropyrimidine dehydrogenase deficiency. Here, we report the case of a patient who initially developed a 5-FU-induced hyperammonemic encephalopathy after receiving FOLFIRINOX (oxaliplatin, irinotecan, folinic acid, and 5-FU) chemotherapy with bevacizumab to treat a metastatic gastrointestinal cancer of unknown primary. Thereafter, the patient was rechallenged successfully by the same chemotherapy regimen (FOLFIRINOX) for more than 6 months with a protocol consisting in a free protein diet, and administration of ammonium chelators, and Krebs and urea cycle intermediates, to prevent further hyperammonemia. We also present a review of the literature on 5-FU rechallenge after 5-FU-induced hyperammonemic encephalopathy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Brain Diseases; Female; Fluorouracil; Gastrointestinal Neoplasms; Humans; Hyperammonemia; Irinotecan; Leucovorin; Neoplasms, Unknown Primary; Oxaliplatin; Prognosis; Retreatment

A case of hyperammonemia induced by chemotherapy, including high-dose fluorouracil(5-FU), for advanced unresectable large intestinal cancer has been reported. This case involved an 81-year-old female who was diagnosed with pT4bcN2M1 (multiple hepatic metastases; stage Ⅳ; KRAS: mutant)after emergency surgery for sigmoid colon cancer and diffuse peritonitis. Post-operation, the 4 courses of mFOLFOX6 plus Bmab therapy was started for advanced unresectable recurrent large intestinal cancer; 48 hours later, she developed consciousness disorder(JCS Ⅲ-300). The disorder promptly disappeared after discontinuation of high-dose 5-FU. Because high-dose 5-FU was inferred to be the main cause of hyperammonemia, XELOX plus Bmab therapy was started as a post-treatment. She did not develop hyperammonemia; therefore, 8 courses were administered. The patient is being followed-up now.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Consciousness Disorders; Female; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Liver Neoplasms; Sigmoid Neoplasms

Systemic chemotherapy based on 5-fluorouracil (5-FU) is a standard treatment for unresectable or recurrent colorectal cancer. Although hyperammonemia is known as one of the adverse side effects of 5-FU, a disturbance of consciousness caused by hyperammonemia is not a usual finding. We encountered a case of 5-FU-related consciousness disturbance with respiratory depression. A woman in her sixties was diagnosed with metastatic cecum cancer, involving peritoneal dissemination and hydronephrosis due to retroperitoneal invasion. After resection of the primary lesion, systemic chemotherapy, including capecitabine, irinotecan, bevacizumab and cetuximab, was administered for the metastatic lesions. As a third-line of treatment, the mFOLFOX6 plus bevacizumab regimen was administered. On the second day of the first course, the patient complained of nausea and vomiting. On third day, her consciousness level was deteriorating. The level of ammonia in the blood was abnormally high. Therefore, we diagnosed consciousness disturbance caused by hyperammonemia resulting from high-dose 5-FU infusion. The symptom improved immediately after mechanical ventilation and intravenous infusion. Renal dysfunction is considered a risk factor for hyperammonemia caused by 5-FU, and it is necessary to pay particular attention in patients with renal dysfunction who receive chemotherapy with 5-FU.

Topics: Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Colectomy; Consciousness; Female; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Nausea; Organoplatinum Compounds; Peritoneal Neoplasms

Patients undergoing mFOLFOX6 treatment were classified into a hyperammonemia group (NH3 group) or a non-hyperammonemia group (Non-NH3 group) in order to investigate risk factors related to the onset of hyperammonemia. The NH3 group demonstrated significantly lower lymphocyte counts, hemoglobin and albumin levels, and estimated glomerular filtration rates compared to the Non-NH3 group, suggesting that the NH3 group was experiencing renal dysfunction and loss of skeletal muscle mass due to malnutrition. Amino acid fractionation in the NH3 group revealed high urea levels, and delayed urea excretion was identified. Fluorocitric acid, a fluorouracil metabolite, inhibits aconitase in the tricarboxylic acid cycle. In addition, decreased renal urea transporter function due to renal impairment leads to delayed urea excretion. These factors may induce secondary decreases in urea cycle function, leading to hyperammonemia.

Topics: Aged; Amino Acids; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Female; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Male; Organoplatinum Compounds; Risk Factors

We report a case of hyperammonemic encephalopathy related to 5-FU in an aged patient with recurrent colon cancer treated with FOLFIRI therapy. An 80-year-old man underwent right hemicolectomy for cecal cancer. After 10 months, surgical resection was performed for its local recurrence. He was then treated with FOLFIRI therapy, and during the fifth course, he presented with a sudden onset of congestive disturbances. Through radiographic examination and laboratory data, only hyperammonemia was found; he was therefore diagnosed with hyperammonemic encephalopathy. By starting branchedamino acid solutions for its treatment, his consciousness and serum ammonia were promptly improved. Hyperammonemic encephalopathy related 5-FU is caused by increasing ammonia production and its metabolic inhibition, and is worsened by renal dysfunction, dehydration, constipation, infections, or body weight loss. On account of the potential decrease of metabolic function of liver and kidney, an aged person tends to have hyperammonnemia more than a youth. Clinicians should be aware of the adverse events associated with hyperammonemia when then administer a large amount of 5-FU to elderly patients.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Brain Diseases, Metabolic; Camptothecin; Combined Modality Therapy; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Male; Recurrence

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Fatal Outcome; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neurotoxicity Syndromes; Organoplatinum Compounds; Oxaliplatin

We report a rare case of metastatic colorectal cancer who suffered from hyperammonemic encephalopathy induced by 5- FU and was continuously treated with FOLFOX therapy. A 50-year-old man with ileus was diagnosed with ascending colon cancer Stage IV, and a right hemicolectomy was performed. Postoperative chemotherapy with modified FOLFOX6 was performed. Complications of nausea and vomiting were seen on day 2 , with confusion and cognitive disturbances on day 3 . None of the other radiographic examinations provided an explanation for his symptoms. Laboratory examination revealed hyperammonemia, so branched-chain amino acid solutions and high-volume drip infusion were started for its treatment. His symptoms entirely disappeared on day 4. We changed to chemotherapy for FOLFOX4 using branched-chain amino acid solutions and drip infusion. The tumor marker level normalized following two courses, and CT following ten courses showed that the size of the lung metastasis and abdominal lymph node had reduced significantly. The patient is currently receiving FOLFOX4.

Topics: Amino Acids, Branched-Chain; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Combined Modality Therapy; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Tomography, X-Ray Computed

FOLFOX therapy is a commonly used chemotherapeutic regimen against recurrent and unresectable colon cancer. However, its acute neurotoxicity is rare and not well recognized. We herein report a case of mFOLFOX6-induced hyperammonemic encephalopathy in a patient having recurrent colon cancer. A 74-year-old female with a history of sigmoid colon cancer was diagnosed as liver, lung, and peritoneal recurrences by surveillance CT and PET/CT. She was initially treated with modified FOLFOX6 therapy. After completing treatment, she presented with sudden onset of confusion, cognitive disturbances, and repeated seizures. None of the other radiographic examinations and laboratory tests provided an explanation for her symptoms except hyperammonemia. She was treated with branched-chain amino acid solutions and high-volume drip infusion, 6 hours after which the encephalopathy resolved. Clinicians should be aware of the adverse hyperammonemia induced by mFOLFOX6 when patients treated with mFOLFOX6 present with neurological disorders.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Diseases, Metabolic; Colonic Neoplasms; Female; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Organoplatinum Compounds; Positron-Emission Tomography; Recurrence; Tomography, X-Ray Computed

A 50-year-old man undergoing operations for sigmoid colon cancer, small intestine invasion, and liver metastasis was given adjuvant chemotherapy postoperatively. During the course, lung, brain and bone metastasis were found, FOLFIRI therapy was started. Fifth FOLFIRI therapy was performed, but on the night of the next day, he was transported on an emergency basis to our hospital because of a coma. Laboratory examination revealed hyperammonemia, so aminoleban was started for its treatment. After 3 days in the hospital, consciousness and serum ammonia were improved. Cases of hyperammonemia caused by 5-FU have been reported in the literature, and this case was diagnosed with the same. Hyperammonemia should be taken into account as a differential diagnosis in the disturbance of consciousness in chemotherapy.

Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Colonic Neoplasms; Consciousness Disorders; Fluorouracil; Humans; Hyperammonemia; Irinotecan; Leucovorin; Male; Middle Aged