A phase II trial of ixabepilone in Asian patients with advanced gastric cancer previously treated with fluoropyrimidine-based chemotherapy

Abstract

PurposeThe highest rates of gastric cancer occur in Eastern Asia. Fluoropyrimidine-based therapy is used initially in unresectable and metastatic disease, but no single standard of care exists following disease progression. Ixabepilone, an epothilone B analog, is a non-taxane microtubule-stabilizing agent with clinical activity across multiple tumor types approved by the United States Food and Drug Administration for treatment of metastatic breast cancer.MethodsAsian patients with unresectable or metastatic gastric adenocarcinoma who had failed fluoropyrimidine-based chemotherapy received ixabepilone 40 mg/m2 by 3-h intravenous infusion every 3 weeks. The primary endpoint was objective response rate (ORR).ResultsFifty-two patients were treated (65.4 % men; median age: 56.5 years). The ORR was 15.4 % (95 % confidence interval [CI] 6.9–28.1); 8 patients achieved partial responses for a median duration of 3.1 months (95 % CI 2.6–4.1 months) and 26 patients (50.0 %) had stable disease. Median progression-free survival was 2.8 months (95 % CI 2.1–3.5 months). The most common grade 3 non-hematological toxicities were fatigue (9.6 %), decreased appetite (7.7 %), sensory neuropathy (5.8 %), and diarrhea (5.8 %). Grade 3/4 neutropenia occurred in 46.2 % of patients.ConclusionsIxabepilone is active in Asian patients with advanced gastric cancer and shows a toxicity profile similar to those previously reported in other tumor types.

Integrative omics analysis reveals effective stratification and potential prognosis markers of pan-gastrointestinal cancers

“…TUBA1C is an apoptosis-related target, being the target of many known drugs ( Wang et al., 2019 ), including two important drugs, epothilone D, and patupilone. Epothilone D was investigated for use in colorectal cancer ( Lee et al., 2007 ), and patupilone was also investigated for treatment in gastric cancer ( Kim et al., 2012 ). SERPINB5 is a target of the p53 signal pathway, which has been associated with colorectal tumor ( Chang et al., 2018 ; Li et al., 2017 ), hepatocellular carcinoma ( Yang et al., 2016 ), and gastric tumor ( Lei et al., 2011 ).…”

Prediction of Cancer Drugs by Chemical-Chemical Interactions

“…Moreover, ixabepilone was reported to be active against advanced or metastatic gastric cancers [130], [131].…”

“…Ixabepilone (DB04845) is investigated for the treatment of breast cancer, head and neck cancer, lung cancer, and so on [129] . Moreover, ixabepilone was reported to be active against advanced or metastatic gastric cancers [130] , [131] .…”

Comparative Assessment of Skin and Subcutaneous Toxicity in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX

“…A platinum agent in combination with fluoropyrimidines is usually employed in metastatic disease setting (Kim et al, 2012), however the therapeutic efficacy and relative toxicity differs markedly in different doses, combinations, schedules of administration and routes of administration (Bano et al, 2012a) and is modulated by immediate or cumulative doses (Bano et al, 2012b). Hand and foot syndrome (HFS), also referred to as palmar-plantar erythrodysesthesia, is reported in patients treated with Oxaliplatin based schedules with and without 5FU (Zhang et al, 2012).…”