The safety and efficacy outcomes of Minnelide given alone or in combination with paclitaxel in advanced gastric cancer: A phase I trial Journal Article
| Authors: | Lim, S. H.; Saluja, A.; Vickers, S.; Hong, J. Y.; Kim, S. T.; Lavania, S.; Pandey, S.; Gupta, V. K.; Velagapudi, M. R.; Lee, J. |
| Article Title: | The safety and efficacy outcomes of Minnelide given alone or in combination with paclitaxel in advanced gastric cancer: A phase I trial |
| Abstract: | Minnelide is a water-soluble disodium salt variant of triptolide, an HSP70 inhibitor that can prevent tumor progression and induce apoptosis. Maximum tolerated dose (MTD), safety, and antitumor activity of Minnelide alone and its combination with paclitaxel were evaluated in this open-label, single-center, dose-escalation phase I study (NCT05566834) in patients who were previously treated for advanced gastric cancer (AGC). Minnelide was administered orally using a 3 + 3 dose-escalation design as monotherapy (Regimen A), and in combination with paclitaxel (Regimen B & C). Our results show that no patients experienced dose limiting toxicity (DLT) in the combination group (Regimen B& C) while 2 patients experienced DLT from the Regimen A group (n = 11) (Minnelide 1.5 mg). The MTD was Minnelide 1.25 mg once daily for 21days Q4 weeks as monotherapy. The most common Grade ≥3 AEs were neutropenia (19.4 %) and abdominal pain (11.1 %). In Regimen C, 71.5 % achieved either a partial response or a stable disease with the median PFS of 4.5 months, and the median OS of 10.7 months. The combination of Minnelide plus paclitaxel as salvage treatment in AGC patients showed meaningful clinical activity with a manageable safety profile. Based on these encouraging results, a phase II study is being initiated to test the effectiveness of the combination regimen in patients with advanced gastric cancer. © 2024 |
| Keywords: | adult; clinical article; treatment response; aged; middle aged; unclassified drug; overall survival; drug tolerability; fatigue; neutropenia; drug efficacy; drug safety; paclitaxel; follow up; antineoplastic agent; anorexia; adenocarcinoma; progression free survival; apoptosis; neutrophil count; tumor volume; heart disease; nausea; vomiting; epidermal growth factor receptor 2; creatinine; hemoglobin; antineoplastic activity; histology; abdominal pain; pruritus; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; microsatellite instability; stomach cancer; weakness; maximum tolerated dose; heart arrhythmia; tumor growth; disease exacerbation; signet ring carcinoma; platelet count; gastric cancer; salvage treatment; heat shock protein; human; male; female; article; minnelide |
| Journal Title: | Cancer Letters |
| Volume: | 597 |
| ISSN: | 0304-3835 |
| Publisher: | Elsevier Ireland Ltd. |
| Date Published: | 2024-08-10 |
| Start Page: | 217041 |
| Language: | English |
| DOI: | 10.1016/j.canlet.2024.217041 |
| PROVIDER: | scopus |
| PUBMED: | 38866072 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
