{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["26(11)"],"submitter":["Taniguchi H"],"funding":["Dainippon Sumitomo Pharma"],"pubmed_abstract":["<h4>Background</h4>Napabucasin is an oral NAD(P)H:quinone oxidoreductase 1 bioactivatable agent that generates reactive oxygen species, is hypothesised to affect multiple oncogenic cellular pathways, including STAT-3, and is expected to result in cancer cell death. This phase I study investigated the safety, tolerability, and pharmacokinetics of napabucasin co-administered with fluorouracil, l-leucovorin, and irinotecan (FOLFIRI) chemotherapy plus bevacizumab in Japanese patients with metastatic colorectal cancer (CRC).<h4>Methods</h4>Patients with histologically confirmed unresectable stage IV CRC received oral napabucasin 240 mg twice daily (BID). Intravenous FOLFIRI and bevacizumab therapy was initiated on day 3 at approved doses. Unacceptable toxicity was evaluated over the first 30 days of treatment, after which treatment continued in 14-day cycles until toxicity or disease progression. Endpoints included safety, pharmacokinetics, and tumour response based on RECIST v1.1.<h4>Results</h4>Four patients received treatment; three were evaluable during the unacceptable toxicity period. All four patients experienced diarrhoea and decreased appetite (considered napabucasin-related in four and two patients, respectively), and three patients experienced neutrophil count decreased. No unacceptable toxicity was reported during the 30-day evaluation period. No grade 4 events, deaths, or serious adverse events were reported. The addition of FOLFIRI and bevacizumab to napabucasin did not significantly change the pharmacokinetic profile of napabucasin; however, results were variable among patients. The best overall response was stable disease in two patients (50.0%).<h4>Conclusions</h4>Napabucasin 240 mg BID in combination with FOLFIRI and bevacizumab was tolerated, with a manageable safety profile in Japanese patients with metastatic CRC."],"journal":["International journal of clinical oncology"],"pagination":["2017-2024"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8520863"],"repository":["biostudies-literature"],"pubmed_title":["Phase I study of napabucasin in combination with FOLFIRI + bevacizumab in Japanese patients with metastatic colorectal cancer."],"pmcid":["PMC8520863"],"pubmed_authors":["Masuishi T","Kawazoe A","Kageyama R","Taniguchi H","Kadowaki S","Iino S","Muro K","Bando H","Yoshino T"],"additional_accession":[]},"is_claimable":false,"name":"Phase I study of napabucasin in combination with FOLFIRI + bevacizumab in Japanese patients with metastatic colorectal cancer.","description":"<h4>Background</h4>Napabucasin is an oral NAD(P)H:quinone oxidoreductase 1 bioactivatable agent that generates reactive oxygen species, is hypothesised to affect multiple oncogenic cellular pathways, including STAT-3, and is expected to result in cancer cell death. This phase I study investigated the safety, tolerability, and pharmacokinetics of napabucasin co-administered with fluorouracil, l-leucovorin, and irinotecan (FOLFIRI) chemotherapy plus bevacizumab in Japanese patients with metastatic colorectal cancer (CRC).<h4>Methods</h4>Patients with histologically confirmed unresectable stage IV CRC received oral napabucasin 240 mg twice daily (BID). Intravenous FOLFIRI and bevacizumab therapy was initiated on day 3 at approved doses. Unacceptable toxicity was evaluated over the first 30 days of treatment, after which treatment continued in 14-day cycles until toxicity or disease progression. Endpoints included safety, pharmacokinetics, and tumour response based on RECIST v1.1.<h4>Results</h4>Four patients received treatment; three were evaluable during the unacceptable toxicity period. All four patients experienced diarrhoea and decreased appetite (considered napabucasin-related in four and two patients, respectively), and three patients experienced neutrophil count decreased. No unacceptable toxicity was reported during the 30-day evaluation period. No grade 4 events, deaths, or serious adverse events were reported. The addition of FOLFIRI and bevacizumab to napabucasin did not significantly change the pharmacokinetic profile of napabucasin; however, results were variable among patients. The best overall response was stable disease in two patients (50.0%).<h4>Conclusions</h4>Napabucasin 240 mg BID in combination with FOLFIRI and bevacizumab was tolerated, with a manageable safety profile in Japanese patients with metastatic CRC.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Nov","modification":"2024-11-15T01:44:54.012Z","creation":"2022-02-11T12:23:03.692Z"},"accession":"S-EPMC8520863","cross_references":{"pubmed":["34291369"],"doi":["10.1007/s10147-021-01987-9"]}}