A multicentre, open-label phase II study of Irinotecan, capecitabine (Xeloda®), and Oxaliplatin (IXO) as first-line treatment in patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma
| Autor: | Arthur Lui, Rakesh Goel, Hagen F. Kennecke, M. Vickers, Jose Gerard Monzon, Larissa J. Vos, Jennifer L. Spratlin, Horia Marginean, J. Maroun, Christine Brezden-Masley, Anthony Fields, Sunita Ghosh, Karen E. Mulder |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Esophageal Neoplasms Maximum Tolerated Dose Nausea medicine.medical_treatment Phases of clinical research Adenocarcinoma Neutropenia Irinotecan Gastroenterology Drug Administration Schedule Capecitabine Young Adult 03 medical and health sciences 0302 clinical medicine Stomach Neoplasms Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Pharmacology (medical) Adverse effect Aged Aged 80 and over Pharmacology Chemotherapy business.industry Middle Aged medicine.disease Oxaliplatin 030104 developmental biology Oncology 030220 oncology & carcinogenesis Female Esophagogastric Junction medicine.symptom business medicine.drug |
| Zdroj: | Investigational New Drugs. 36:674-682 |
| ISSN: | 1573-0646 0167-6997 |
| Popis: | Purpose Chemotherapy remains the primary treatment for metastatic gastric/GEJ cancer but optimal agents and schedule remain controversial. This study examined the safety and efficacy of first-line Irinotecan, capecitabine (Xeloda®), and Oxaliplatin (IXO). Patients and Methods Eligible patients with HER2-unamplified/unknown, metastatic gastric/GEJ adenocarcinoma were treated with 21-day cycle IXO at dose level 1 (DL1: Day 1 O-100 mg/m2 & I-160 mg/m2 IV, Day 2–15 X-1900 mg/m2/day PO divided doses) or modified IXO (mIXO): Day 1 O-85 mg/m2 & I-120 mg/m2 IV, Day 2–15 X-1425 mg/m2/day PO divided doses). This Bryant and Day two-stage designed study had dual primary endpoints of objective response rate (ORR) and toxicity. Secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results Fifty patients were enrolled and received a median of 7 cycles. After accrual of 9 patients at DL1, evaluable RR was 88% however dose limiting toxicity (DLT) rate was 56% thus doses were adjusted to mIXO. Fifteen patients accrued at mIXO had a RR of 60% and DLT rate of 13% allowing continuation to stage 2. Overall, 48 and 49 patients were evaluable for efficacy and safety, respectively, with ORR of 54% and DLTs in 24% of patients (DL1 = 56%; mIXO = 18%). Disease control rate was 85%. The most frequent grade 3/4 adverse events were diarrhea, neutropenia, fatigue, hypokalemia, and nausea. Median PFS and OS were 7.5 and 13.0 months, respectively, with a median follow-up of 9.7 months. Conclusion mIXO demonstrates promising ORR, PFS, OS, and acceptable toxicity compared to standard triplet regimens. IXO should be evaluated in phase III trials. |
| Databáze: | OpenAIRE |
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