Immunotherapy for Unresectable Small Bowel Adenocarcinoma: A Case Series.

BACKGROUND/AIM: The efficacy of systemic therapy for unresectable small bowel adenocarcinoma that is refractory to fluoropyrimidines and oxaliplatin has not yet been established because of the rarity of this cancer. Although immunotherapy with anti-PD-1 antibodies has shown robust efficacy in the treatment of esophagogastric adenocarcinoma, its effectiveness in small bowel adenocarcinoma remains unclear. CASE REPORT: In the first case, a 75-year-old man was diagnosed with metastatic moderately differentiated adenocarcinoma of the jejunum with stable microsatellite instability. After receiving multiple lines of therapy, including fluoropyrimidines plus oxaliplatin, irinotecan, and paclitaxel, the patient was treated with nivolumab and achieved a partial response that lasted for 12 months. In the second case, a 65-year-old man was diagnosed with an unresectable locally advanced duodenal adenocarcinoma. High microsatellite instability was confirmed by polymerase chain reaction-based testing. After showing resistance to 5-fluorouracil and oxaliplatin, the patient received nivolumab and ipilimumab therapy. Although therapy was discontinued because of immune-related colitis and skin rash, a partial response was achieved. CONCLUSION: Treatment with immune checkpoint inhibitors is effective for refractory small bowel adenocarcinoma, irrespective of the microsatellite status.

A Phase II Trial of Trifluridine/Tipiracil in Combination with Cetuximab Rechallenge in Patients with RAS Wild-Type mCRC Refractory to Prior Anti-EGFR Antibodies: WJOG8916G Trial.

BACKGROUND: Trifluridine/tipiracil (FTD/TPI) improved the overall survival in patients with metastatic colorectal cancer (mCRC) who had previously received standard chemotherapies; however, the clinical outcomes remain poor. OBJECTIVE: A multicenter phase II study aimed to assess the efficacy and safety of FTD/TPI plus cetuximab rechallenge. PATIENTS AND METHODS: Patients with histologically confirmed RAS wild-type mCRC refractory to prior anti-epidermal growth factor receptor (anti-EGFR) antibody were enrolled and treated with FTD/TPI (35 mg/m2 twice daily on days 1-5 and 8-12) plus cetuximab (initially 400 mg/m2, followed by weekly 250 mg/m2) every 4 weeks. The primary endpoint was disease control rate (DCR), expecting a target DCR of 65% and null hypothesis of 45% with 90% power and 10% one-sided alpha error. Gene alterations of RAS, BRAF, EGFR, PIK3CA, ERBB2, and MET in pre-treatment circulating tumor DNA were evaluated using the Guardant360 assay. RESULTS: A total of 56 patients (median age 60 years; left-sided tumors 91%; objective partial or complete response during the prior anti-EGFR therapy 61%) were enrolled. The DCR was 54% (80% confidence interval [CI] 44-63; P = 0.12), with a partial response rate of 3.6%. Median progression-free survival (PFS) was 2.4 months (95% CI 2.1-3.7). In the circulating tumor DNA analysis, patients without any alterations of the six genes (n = 20) demonstrated higher DCR (75% vs. 39%; P = 0.02) and longer PFS (median 4.7 vs. 2.1 months; P < 0.01) than those with any gene alterations (n = 33). The most common grade 3/4 hematologic adverse event was neutropenia (55%). No treatment-related deaths occurred. CONCLUSIONS: FTD/TPI plus cetuximab rechallenge did not demonstrate clinically meaningful efficacy in all mCRC patients, but might be beneficial for the molecularly selected population.

[Perspective and Usage of the Clinical Guideline of Oncology from the Viewpoint of a Medical Oncologist Working at a Community Hospital].

Because of the diversity of cancer biology and multiple treatment options, which include focal therapy(surgical resection and radiotherapy)and systemic therapy, oncology practice is complicated and always challenging for oncologists and patients. To decide on an evidence-based optimal therapy, clinical guideline has a crucial role for physicians. However, there are discrepancies in the contents and accessibility to the guidelines among each. This article mentions the role of guidelines and how they are adapted into practice from the viewpoint of a medical oncologist working at a community hospital.

The Impact of Nutritional Support on Survival Outcomes in Patients with Advanced Gastric Adenocarcinoma Treated with Chemotherapy.

Malnutrition and cachexia occur commonly in patients with advanced gastric cancer (AGC). This study elucidated the effect of nutritional support (NS) on survival outcomes among patients with AGC undergoing chemotherapy. We retrospectively evaluated new AGC cases at our institute between January 2015 and January 2021. Inclusion criteria were unresectable or recurrent chemotherapy-treated gastric adenocarcinoma, ECOG performance status (PS) 0-2, and adequate organ function. Time to treatment failure (TTF) and overall survival (OS) were evaluated, and univariate and multivariate analyses identified prognostic factors. A total of 103 eligible patients were separated into groups: 69 patients (67%) into NS and 34 (33%) into routine care (RC). The median follow-up time was 11.0 mo, (0.5-92). NS was offered to patients with poorer PS (p = 0.03), Glasgow prognostic score (GPS) positivity (p = 0.001), and high neutrophil-to-lymphocyte ratios (cut-off ≤ 3, p = 0.02). Median OS and TTF in the RC and NS groups were 11.6 and 10.4 mo, (p = 0.99) and 4.2 and 5.5 mo, (p = 0.07), respectively. Multivariate analyses identified NS (hazard ratio [HR] = 0.53, p = 0.01) and GPS positivity for TTF, and low body mass index (HR = 2.03, p = 0.007) and GPS positivity (HR = 2.25, p = 0.001) for OS as significant prognostic factors. Thus, NS with chemotherapy is a potentially effective intervention for AGC.

Thoracic SMARCA2-deficient But SMARCA4-preserved Tumors With Undifferentiated Morphology Combined With Claudin-4 Negativity.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently recognized tumor characterized by inactivation of SMARCA4, a SWItch/Sucrose NonFermentable chromatin remodeler, detectable by immunohistochemistry. SMARCA4-UT shows undifferentiated or rhabdoid morphology with claudin-4 negativity. However, thoracic undifferentiated tumors with the same histologic features as SMARCA4-UTs but a preserved SMARCA4 expression have so far been underrecognized. We herein report 3 cases of thoracic undifferentiated tumors with isolated loss of SMARCA2 but retained expression of SMARCA4 and SMARCB1. The present tumors were found in 2 men and 1 woman, 40 to 50 years old. All patients were heavy smokers (≥20 pack-years). The tumors were generally large masses located in the mediastinum, lung>chest wall, or lung and composed of relatively monotonous, round to epithelioid cells with variably rhabdoid cells. Immunohistochemically, the tumors showed claudin-4 negativity with variable expression of cytokeratin. All cases showed highly aggressive clinical behavior with overall survival of 2 to 10 months. These SMARCA2-deficient tumors with preserved SMARCA4 expression appeared to be clinicopathologically indistinguishable from SMARCA4-UTs, except for in their SMARCA4 status. This variant may expand the spectrum of SWItch/Sucrose NonFermentable-deficient undifferentiated tumors of the thoracic region beyond SMARCA4-UT.

Successful Alectinib Treatment for Carcinoma of Unknown Primary with EML4-ALK Fusion Gene: A Case Report.

Gene alteration in anaplastic lymphoma kinase (ALK) is rare, and the efficacy of ALK inhibitors in the treatment of carcinoma of unknown primary (CUP) with ALK alteration remains unclear. The patient was a 56-year-old woman who presented with cervical lymph node swelling. Computed tomography revealed paraaortic, perigastric, and cervical lymph node swelling; ascites; a liver lesion; and a left adrenal mass. A cervical lymph node biopsy was performed, and pathological diagnosis of an undifferentiated malignant tumor was conducted. Finally, the patient was diagnosed with CUP and treated with chemotherapy. To evaluate actionable mutations, we performed a multigene analysis, using a next-generation sequencer (FoundationOne® CDx). It revealed that the tumor harbored an echinoderm microtubule-associated protein-like 4 (EML4) and ALK fusion gene. Additionally, immunohistochemistry confirmed ALK protein expression. Alectinib, a potent ALK inhibitor, was recommended for the patient at a molecular oncology conference at our institution. Accordingly, alectinib (600 mg/day) was administered, and the multiple lesions and symptoms rapidly diminished without apparent toxicity. The administration of alectinib continued for a period of 10 months without disease progression. Thus, ALK-tyrosine kinase inhibitors should be considered in patients with CUP harboring the EML4-ALK fusion gene.

Efficacy of trastuzumab deruxtecan in an advanced gastric cancer patient with brain metastasis.

BACKGROUND: There is no clinical evidence supporting the effectiveness of trastuzumab deruxtecan (T-DXd) for treating advanced gastric cancer (AGC) with brain metastasis. CASE REPORT: This is a case of a 65-year-old man with human epidermal growth factor-2 (HER2)-positive AGC. He was initially treated with capecitabine, cisplatin, and trastuzumab, followed by paclitaxel and ramucirumab, nivolumab, trifluridine and tipiracil, and irinotecan regimens in addition to radiation therapy for brain metastasis. The patient exhibited refractoriness to the standard regimen used for AGC and developed relapse of the brain metastasis after radiation accompanied by headache, nausea, and dizziness. In August 2020, following the approval of T-DXd for HER2-positive AGC, he received T-DXd therapy. After 5 cycles of T-DXd, contrast-enhanced computed tomography and magnetic resonance imaging demonstrated significant tumor shrinkage and improvement of symptoms. CONCLUSION: T-DXd demonstrated effectiveness for the treatment of brain metastasis arising from HER2-positive AGC.

A triplet combination of FOLFOXIRI plus cetuximab as first-line treatment in RAS wild-type, metastatic colorectal cancer: a dose-escalation phase Ib study.

BACKGROUND: The triplet-agent (5-fluorouracil/leucovorin, oxaliplatin, and irinotecan; FOLFOXIRI) combined with an anti-epidermal growth factor receptor antibody as a first-line treatment of metastatic colorectal cancer (mCRC) has shown promising results in Western trials. This phase Ib study assessed the safety of FOLFOXIRI plus cetuximab in Japanese patients with RAS wild-type mCRC. METHODS: Patients with previously untreated RAS wild-type mCRC received weekly cetuximab (400 mg/m2 at week 1 and subsequently 250 mg/m2) plus FOLFOXIRI that consisted of irinotecan (100, 120, and 150 mg/m2 defined as dose levels 0, 1, and 2), followed by oxaliplatin 85 mg/m2 and l-leucovorin 200 mg/m2 and then 5-fluorouracil 2400 mg/m2. The dose level of irinotecan was escalated starting at dose level 1 in a 3 + 3 manner. The primary endpoint was to determine the maximum-tolerated dose (MTD) and the recommended phase-2 dose (RP2D). Secondary endpoints included safety, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). RESULTS: Nine patients were enrolled. The MTD was not reached at dose level 2 and the RP2D was 150 mg/m2 irinotecan. The most frequent grade 3/4 adverse events were neutropenia (44%), fatigue (11%), paronychia (22%), and acneiform rash (11%). No dose-limiting toxicities occurred in any of the enrolled patients. No treatment-related death was observed. The ORR was 89% (95% confidence interval 52-100%). CONCLUSION: The safety profile of the combination of cetuximab and FOLFOXIRI was acceptable and promising anti-tumor activity was demonstrated, supporting further study in patients with RAS wild-type mCRC.

Salvage Chemotherapy by FOLFIRI Regimen for Poorly Differentiated Gastrointestinal Neuroendocrine Carcinoma.

PURPOSE: Chemotherapy is the mainstay treatment for advanced poorly differentiated gastrointestinal neuroendocrine carcinoma (GI-NEC), with platinum-containing regimens being the optimal first-line regimen. However, the role and efficacy of second-line chemotherapy for GI-NEC are unclear. This study aimed to evaluate the feasibility and efficacy of fluorouracil, leucovorin, and irinotecan (FOLFIRI) as second-line therapy in patients with relapsed or recurrent GI-NEC after first-line platinum plus etoposide therapy. METHODS: We retrospectively evaluated eight consecutive patients with unresectable GI-NEC treated between 2017 and 2020. The inclusion criteria were pre-treatment with platinum doublet therapy, performance status (PS) 0-2, having measurable lesions, and treatment with FOLFIRI as second-line therapy. The overall response rate, progression-free survival (PFS), overall survival (OS), safety, and relative dose intensity were evaluated. RESULTS: Five patients met the inclusion criteria. Overall, 37 cycles of FOLFIRI were administered. The relative dose intensities for irinotecan, continuous infusion of 5-FU, and a bolus injection of 5-FU were 76%, 72%, and 54%, respectively. Overall, 2 of the 5 patients achieved partial response (40%), and the duration of response (DOR) was 4.0 months. The PFS and OS rates were 5.8 (95% CI, 1.5-NA) and 11 (95% CI, 6.3-NA) months, respectively. Overall, 4 of the 5 patients (80%) proceeded with further chemotherapy. Grade ≥ 3 adverse events except hematological toxicity included febrile neutropenia (n = 2), anorexia (n = 2), and fatigue (n = 1). Treatment discontinuation due to treatment-related adverse events was not observed. CONCLUSIONS: FOLFIRI showed modest efficacy and feasibility for GI-NEC patients and has thus potential for patients who fail the first-line treatment.

[Sarcopenia and Nutrition Support in the Treatment of Gastric Cancer].

Sarcopenia is regarded with a negative prognostic or detrimental factor for several diseases, regardless of benign or malignant disease. The relationship between sarcopenia and resectable gastric cancer has been investigated gradually. On the contrary, the effect of sarcopenia in advanced gastric cancer is not apparent. In this article, firstly, we summarised the impact of sarcopenia in resectable stage, and then in advanced gastric cancer receiving chemotherapy. Finally, we discussed the nutrition support for advanced gastric cancer.

Prospective Survey of Financial Toxicity Measured by the Comprehensive Score for Financial Toxicity in Japanese Patients With Cancer.

PURPOSE: We previously reported on the pilot study assessing the feasibility of using the Japanese translation of the Comprehensive Score for Financial Toxicity (COST) tool to measure financial toxicity (FT) among Japanese patients with cancer. In this study, we report the results of the prospective survey assessing FT in Japanese patients with cancer using the same tool. PATIENTS AND METHODS: Eligible patients were receiving chemotherapy for a solid tumor for at least 2 months. In addition to the COST survey, socioeconomic characteristics were collected by using a questionnaire and medical records. RESULTS: Of the 191 patients approached, 156 (82%) responded to the questionnaire. Primary tumor sites were colorectal (n = 77; 49%), gastric (n = 39; 25%), esophageal (n = 16; 10%), thyroid (n = 9; 6%), head and neck (n = 4; 3%), and other (n = 11; 7%). Median COST score was 21 (range, 0 to 41; mean ± standard deviation, 12.1 ± 8.45), with lower COST scores indicating more severe FT. On multivariable analyses using linear regression, older age (ß, 0.15 per year; 95% CI, 0.02 to 0.28; P = .02) and higher household savings (ß, 8.24 per ¥15 million; 95% CI, 4.06 to 12.42; P < .001) were positively associated with COST score; nonregular employment (ß, -5.37; 95% CI, -10.16 to -0.57; P = .03), retirement because of cancer (ß, -5.42; 95% CI, -8.62 to -1.37; P = .009), and use of strategies to cope with the cost of cancer care (ß, -5.09; 95% CI, -7.87 to -2.30; P < .001) were negatively associated with COST score. CONCLUSION: Using the Japanese version of the COST tool, we identified various factors associated with FT in Japanese patients with cancer. These findings will have important implications for cancer policy planning in Japan.

Solvent-based paclitaxel or nab-paclitaxel for heavily treated relapsed/refractory small cell lung cancer: Retrospective single-institution observational study.

Treatment options for patients with relapsed/refractory small cell lung cancer (R/R SCLC) are limited, and the efficacy of salvage therapies for heavily treated patients should be assessed. Here, we evaluated the efficacy of paclitaxel (PTX) in R/R SCLC patients.A single-institute retrospective chart review was conducted. The primary endpoint was overall survival (OS), whereas the secondary endpoints were progression-free survival (PFS), overall response rate, disease control rate (DCR), and safety.Thirty-one patients (median age, 69 [range, 56-80] years) were analyzed. The median follow-up period was 122 (range, 28-1121) days. The median OS and PFS were 4.4 and 2.2 months, respectively. Adverse events of grade 3 or higher, other than hematological toxicity, were febrile neutropenia and neuropathy. Multivariate analyses identified the following independent predictors of poor OS: performance status and lactate dehydrogenase at the upper limit of normal.PTX monotherapy showed moderate efficacy with acceptable toxicity in heavily treated patients with R/R SCLC patients.

The impact of the Glasgow Prognostic Score on survival in second-line chemotherapy for metastatic colorectal cancer patients with BRAF V600E mutation.

BACKGROUND: BRAF (v-raf murine sarcoma viral oncogene homolog B1) V600E mutant colorectal cancer is associated with short survival. Recently, clinical trials have been conducted to improve outcomes of second or later lines of chemotherapy. However, there is a paucity of reference data pertaining to outcomes of second-line chemotherapy and prognostic factors that are relevant only to BRAF mutant patients. PATIENTS AND METHODS: We retrospectively reviewed metastatic colorectal cancer patients with BRAF V600E mutation who underwent second-line chemotherapy between January 2007 and March 2017. We evaluated treatment outcomes and performed prognostic analyses. RESULTS: A total of 52 patients were included. The median progression-free survival and overall survival (OS) were 2.5 [95% confidence interval (CI) = 1.91-4.11] and 6.5 (95% CI = 4.30-9.63) months, respectively. Overall response and disease control rates were 7% and 48%, respectively. All the regimens which elicited a partial response included BRAF inhibitors in combination with anti-epidermal growth factor receptor (EGFR) antibodies. Therefore, the overall response was 0% after exclusion of patients treated with study drugs. Multivariate analysis for OS revealed that the Glasgow Prognostic Score (GPS), elevated lactate dehydrogenase, and poor performance status were independent prognostic factors. In particular, survival curves according to the GPS stratified the patients into distinct risk groups. The median OSs in patients with GPS of 0, 1, and 2 were 9.9, 5.0, and 1.9 months, respectively. CONCLUSIONS: Outcomes of second-line chemotherapy for metastatic colorectal cancer patients with BRAF V600E mutation were extremely poor. GPS may be useful in future clinical trials.

Primary Mediastinal HER2-positive Apocrine Carcinoma in Mature Teratoma Treated With Anti-HER2 Therapy and Chemoradiation.

BACKGROUND: There are no established guidelines for the management of apocrine carcinomas of the breast; they are treated as a non-specific type of breast cancer. CASE REPORT: We report on the case of a 40-year-old man who developed primary mediastinal apocrine carcinoma overexpressing human epidermal growth factor-2 (HER2). The patient initially underwent complete resection of a mediastinal mature teratoma with a focal apocrine carcinoma component. Two years after surgery, relapse was detected in multiple mediastinal lymph nodes. He received induction chemotherapy including docetaxel, trastuzumab, and pertuzumab; consolidative concurrent chemoradiation was added after six cycles. A complete response was confirmed using computed tomography following this multimodal therapy. After chemoradiation, adjuvant trastuzumab and pertuzumab were administered for 1 year and the patient has since had no evidence of progressive disease. CONCLUSION: A multi-modal regimen that includes an anti-HER2 agent appears to be a promising treatment for patients with HER2-positive extramammary apocrine carcinoma.

Baseline Sarcopenia and Skeletal Muscle Loss During Chemotherapy Affect Survival Outcomes in Metastatic Gastric Cancer.

AIM: To determine the association between sarcopenia and prognosis in patients with metastatic gastric cancer (mGC) receiving chemotherapy. PATIENTS AND METHODS: Our study retrospectively evaluated 231 consecutive Japanese patients with mGC who commenced first-line chemotherapy at our Institution between January 2013 and December 2015. Muscle loss during chemotherapy was defined as a ≥10% reduction in the skeletal muscle index and was evaluated for its association with time to treatment failure (TTF) and overall survival (OS). RESULTS: Of 118 patients, 89% had baseline sarcopenia and 31% developed muscle loss. Muscle loss was significantly associated with shorter TTF and OS and was an independent prognostic factor for both these parameters; poor performance status and poorer differentiation on histology were also significant predictors of shorter OS. However, muscle loss was not significantly associated with increased grade 3 or higher toxicities. CONCLUSION: Muscle loss during chemotherapy negatively affected survival among patients with mGC.

A prospective survey of comprehensive score for financial toxicity in Japanese cancer patients: report on a pilot study.

BACKGROUND: Financial toxicity (FT) has a negative impact on the quality of life and survival of patients with cancer. The comprehensive score for FT (COST) questionnaire is a tool to measure FT which has already been validated in patients with cancer in the United States. However, the feasibility and validity of assessing FT using the COST questionnaire have not been established in non-US healthcare settings, including that in Japan. METHODS: This is a prospective pilot survey to ascertain the feasibility of using the COST questionnaire to evaluate FT in Japanese patients with advanced solid cancer who had been receiving chemotherapy for at least 2 months. The COST questionnaire was translated into Japanese using Functional Assessment of Chronic Illness Therapy methodology. RESULTS: Of the 12 patients approached, 11 (92%) responded to the questionnaire. The median COST score was 22 (range, 6-29; mean ± SD, 20.18 ± 8.17). Five (45%) and two (18%) patients suffered grade 1 (COST score 14-25) and grade 2 (COST score 1-13) FT, respectively. The COST measure demonstrated good internal consistency with a Cronbach α of 0.87. CONCLUSIONS: The COST measure demonstrated good feasibility in measuring FT in the Japanese healthcare setting. Despite the existing universal health insurance system and ceiling amount for high-cost medical expenses, some Japanese patients experienced meaningful FT during chemotherapy. A prospective study is already underway to confirm the preliminary results (UMIN: 000025043).

FOLFOX as First-line Therapy for Gastric Cancer with Severe Peritoneal Metastasis.

BACKGROUND/AIM: Severe peritoneal metastasis (PM) from advanced gastric cancer (AGC) causes massive ascites and inadequate oral intake. Because patients with severe PM are often not included in clinical trials, little is known regarding the efficacy and safety of oxaliplatin with l-leucovorin and bolus/continuous infusion of 5-fluorouracil (FOLFOX) for them. PATIENTS AND METHODS: We retrospectively studied AGC patients with massive ascites and/or inadequate oral intake due to severe PM treated with FOLFOX as the first-line treatment. RESULTS: Only 39 (10%) of 378 AGC patients had severe PM; 10 received FOLFOX. The median progression-free and overall survivals were 7.5 and 13.2 months, respectively. Ascites decreased in seven of nine patients with ascites, and oral intake improved in four of seven patients with an inadequate oral intake. Common grade 3-4 adverse events included neutropenia and anemia. CONCLUSION: This study suggests that FOLFOX is effective and manageable for AGC patients with severe PM.

Successful Treatment of Cardiac Angiosarcoma Associated with Disseminated Intravascular Coagulation with Nab-Paclitaxel: A Case Report and Review of the Literature.

Angiosarcoma of the heart is an uncommon soft tissue sarcoma. A few cases of disseminated intravascular coagulation (DIC) associated with angiosarcoma occurring in various organs, but not the heart, have been reported. Although taxane is commonly used in the treatment of metastatic angiosarcoma, data on the efficacy of nab-paclitaxel for angiosarcoma are limited. Here, we report probably the first case of a patient with primary cardiac angiosarcoma with coexisting DIC who was successfully treated with nab-paclitaxel. A 62-year-old female with chief complaints of nausea and shortness of breath was diagnosed as having cardiac angiosarcoma with liver metastases. Four months after the resection of her primary tumor, the hepatic metastatic lesions progressed rapidly accompanied by new metastatic lesions in the right iliac bone and signs of DIC. She received nab-paclitaxel as first-line chemotherapy. A response of stable disease was achieved after 2 treatment cycles and DIC was successfully controlled for at least 4 months. This report suggests potential utility of nab-paclitaxel for angiosarcoma complicated with DIC. We also review the literature for all cases of angiosarcoma with DIC reported so far.

Acute hyperammonemic encephalopathy after fluoropyrimidine-based chemotherapy: A case series and review of the literature.

Acute hyperammonemic encephalopathy induced by fluoropyrimidines (FPs) is a rare complication. Its pathophysiology remains unclear, especially given the currently used regimens, including intermediate-doses of 5-fluorouracil (5-FU) or oral FP agents. We aimed to characterize the clinical manifestations in cancer patients who developed hyperammonemic encephalopathy after receiving FP-based chemotherapy.We retrospectively reviewed 1786 patients with gastrointestinal or primary-unknown cancer who received FP-based regimens between 2007 and 2012. Eleven patients (0.6%) developed acute hyperammonemic encephalopathy. The incidence according to the administered anticancer drugs were as follows: 5-FU (8 of 1176, 0.7%), S-1 (1 of 679, 0.1%), capecitabine (2 of 225, 0.9%), and tegafur-uracil (UFT) (0 of 39, 0%). Ten patients (90.9%) had at least 1 aggravating factor, including infection, dehydration, constipation, renal dysfunction, and muscle loss. All the 10 patients met the definition of sarcopenia. Median time to the onset of hyperammonemic encephalopathy in the cycle was 3 days (range: 2-21). Three patients (27.3%) developed encephalopathy during the first cycle of the regimen and the remaining 8 patients during the second or more cycles. Seven patients (63.6%) had received at least 1 other FP-containing regimen before without episodes of encephalopathy.All patients recovered soon after immediate discontinuation of chemotherapy and supportive therapies, such as hydration, infusion of branched-chain amino acids, and oral lactulose intake, with a median time to recovery of 2 days (range: <1-7). Four patients (36.4%) received FP-based regimens after improvement of symptoms; 3 patients were successfully managed with dose reduction, and 1 patient, who had developed encephalopathy due to S-1 monotherapy, received modified FOLFOX-6 therapy without encephalopathy later.FP-associated acute hyperammonemic encephalopathy is extremely rare, but a possible event at any time and even during the administration of oral FP agents. Particular attention is warranted when giving FP-based therapy for patients with aggravating factors, such as sarcopenia. This complication can be properly managed with early detection.