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Cabozantinib is a multi-kinase inhibitor targeting multiple tyrosine kinases. It improves overall survival and progression-free survival in patients previously treated with sorafenib for advanced hepatocellular carcinoma (HCC) compared to the placebo in the phase 3 CELESTIAL trial. A 71-year-old man presented to our hospital for treatment of HCC with chronic hepatitis C. He was refractory to sorafenib, lenvatinib, regorafenib, and ramucirumab and started atezolizumab and bevacizumab therapy in November 2020. After administering the second cycle on December 10, 2020, the patient was diagnosed with progressive disease in January 2021. Therefore, cabozantinib (60 mg/day) was initiated on January 14, 2021. As the grade 3 aspartate aminotransferase and alanine aminotransferase levels increased, grade 3 anorexia and a decline in performance status were observed in the first week, and cabozantinib was terminated. His performance status and anorexia gradually improved, and contrast-enhanced computed tomography (CT) in June 2021 showed complete remission (CR) according to the modified Response Evaluation Criteria in Solid Tumors. The patient did not show disease progression for 11 months without receiving any treatment for HCC. To the best of our knowledge, this is the first report of CR with cabozantinib in advanced HCC., Competing Interests: Declarations. Informed consent: This study does not involve human participants; therefore, the requirement for informed consent was waived., (© 2024. The Author(s).)

Background: The global phase 3 NAPOLI -1 trial of patients with pancreatic ductal adenocarcinoma (PDAC) demonstrated an overall survival (OS) benefit from using liposomal irinotecan and 5-fluorouracil/leucovorin (nal-IRI + 5-FU/LV) after treatment with gemcitabine (GEM) compared to 5-FU/LV alone. However, the efficacy and safety of this regimen in older patients are not well studied., Methods: We conducted a single-center retrospective study to compare the therapeutic efficacy of nal-IRI + 5-FU/LV between older and younger patients with cutoff ages of 70 and 75 years, respectively. We included patients with a prior history of one or more GEM-based regimens for locally advanced or metastatic PDAC and were treated with nal-IRI + 5-FU/LV., Results: Of the 115 patients, 54 (47.0%) and 24 (20.9%) were aged ≥ 70 and ≥ 75 years, respectively. The median OS and progression-free survival (PFS) of the entire cohort were 8.5 and 3.6 months, respectively. No significant differences were observed in OS and PFS hazard ratios using age cutoffs of 70 (P = 0.90 and 0.99, respectively) and 75 (P = 0.90 and 0.76, respectively) years. Additionally, no significant differences were found in the incidence of treatment-related adverse events (trAEs) between patients aged ≥ 70 and < 70 years or those aged ≥ 75 and < 75 years. Other than hematological toxicity, no trAEs higher than Grade 4 were observed in either age group., Conclusion: The efficacy and safety of nal-IRI + 5-FU/LV for patients with PDAC are not significantly different for those aged ≥ 70 years compared to younger patients., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Fluorouracil, leucovorin (5FU/LV), and nanoliposomal-irinotecan (nal-IRI) combination therapy has been established as the second-line treatment for advanced pancreatic ductal adenocarcinoma. Oxaliplatin with 5FU/LV (FOLFOX) is often used as a subsequent treatment, although its efficacy and safety are yet to be fully elucidated. We aimed to evaluate the efficacy and safety of FOLFOX as a third- or later-line treatment for patients with advanced pancreatic ductal adenocarcinoma., Methods: We conducted a single-centre, retrospective study that enrolled 43 patients who received FOLFOX after failure of gemcitabine-based regimen followed by 5FU/LV + nal-IRI therapy between October 2020 and January 2022. FOLFOX therapy consisted of oxaliplatin (85 mg/m 2 ), levo-leucovorin calcium (200 mg/m 2 ) and 5-FU (2400 mg/m 2 ) every 2 weeks per cycle. Overall survival, progression-free survival, objective response, and adverse events were evaluated., Results: At the median follow-up time of 3.9 months in all patients, the median overall survival and progression-free survival were 3.9 months (95% confidence interval [CI], 3.1-4.8) and 1.3 months (95% CI, 1.0-1.5), respectively. Response and disease control rates were 0 and 25.6%, respectively. The most common adverse event was anaemia in all grades followed by anorexia; the incidence of anorexia and grades 3 and 4 was 21 and 4.7%, respectively. Notably, grades 3-4 peripheral sensory neuropathy was not observed. Multivariable analysis revealed that a C-reactive protein (CRP) level of > 1.0 mg/dL was a poor prognostic factor for both progression-free survival and overall survival: hazard ratios were 2.037 (95% CI, 1.010-4.107; p = 0.047) and 2.471 (95% CI, 1.063-5.745; p = 0.036), respectively., Conclusion: FOLFOX as a subsequent treatment after failure of second-line treatment with 5FU/LV + nal-IRI is tolerable, although its efficacy is limited, particularly in patients with high CRP levels., (© 2023. The Author(s).)

Background: The preferred regimen for unresectable pancreatic cancer following gemcitabine-based chemotherapy is not well-established. This study compared the efficacy of (ⅰ) liposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/leucovorin (LV) (nal-IRI/5-FU/LV) versus modified FOLFIRINOX (mFFX) and (ⅱ) nal-IRI/5-FU/LV versus FOLFIRI, respectively, and the safety of the three regimens each other, as second-line chemotherapies for unresectable pancreatic cancer., Methods: This was a retrospective single-center analysis of all patients who were administered nal-IRI/5-FU/LV, mFFX, or FOLFIRI from December 2014 to July 2021 as second-line chemotherapy for pancreatic cancer. The primary endpoint was the overall survival (OS) of all patients, excluding those with locally advanced pancreatic cancer. Regarding safety, we assessed the incidence of grade ≥3 adverse events of interest in all patients., Results: A total of 137 patients (nal-IRI/5-FU/LV, n = 55; mFFX, n = 39; FOLFIRI, n = 43) were included. The median OS in the nal-IRI/5-FU/LV group, the mFFX group, and the FOLFIRI group was 7.4, 11.8, and 8.4 months, respectively. Compared with the nal-IRI/5-FU/LV group, the mFFX and FOLFIRI groups displayed a hazard ratio of 0.66 [95% confidence interval 0.40-1.08] and 0.87 [95% confidence interval 0.55-1.39], respectively. In the FOLFIRI group, the incidence of grade ≥3 treatment-related adverse events tended to be low among all three groups., Conclusions: Given the trend toward longer OS in the mFFX group and the lower incidence of adverse events in the FOLFIRI group, both mFFX and FOLFIRI, as well as nal-IRI/5-FU/LV, can be treatment options for second-line chemotherapy for unresectable pancreatic cancer., Competing Interests: Declaration of competing interest All authors have no known competing financial interests, personal relationships, or competing interests that could have influenced the work reported in this study., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

It is important to consider susceptibility to drug-induced toxicity between animals and humans. Chimeric mice with a humanized liver are expected to predict hepatotoxicity in humans. Drug-induced phospholipidosis (DIPL), in which phospholipids accumulate, is a known entity. In this study, we examined whether chimeric mice can reveal species differences in DIPL. Changes in various phosphatidylcholine (PhC) molecules were investigated in the liver of chimeric mice after administering amiodarone, which induces phospholipidosis. Liquid chromatography-tandem mass spectrometry revealed that levels of PhCs tended to increase in the liver after administration of amiodarone. The liver of chimeric mice consists of human hepatocytes and residual mouse hepatocytes. We used imaging mass spectrometry (IMS) to evaluate the increase of PhCs in human and mouse hepatocytes after administration of amiodarone. IMS visualizes localization of endogenous and exogenous molecules in tissues. The IMS analysis suggested that the localized levels of several PhCs tended to be higher in the human hepatocytes than those in mouse hepatocytes, and PhC levels changed in response to amiodarone. Chimeric mice with a humanized liver will be useful to evaluate species differences in DIPL between mice and humans.

The newly established GUS expression bioassay on the callus extracts of 22 species of plants revealed that the methanol extract of Phytolacca americana callus had the most potent inhibitory activity against agrobacterial plant transformation. A triterpene glycoside phytolaccoside B was isolated from the extract as a genuine plant transformation inhibitor having neither antiagrobacterial nor phytotoxic activity. This compound is promising for use as a biochemical probe for studies on the plant transformation mechanism.