Randomized phase 2 study of gemcitabine and cisplatin with or without vitamin supplementation in patients with advanced esophagogastric cancer
| Autor: | C. J. van Groeningen, Elisa Giovannetti, G.J. Peters, R. Ruijter, Henk M.W. Verheul, Giuseppe Giaccone, A. A. van Zweeden, Richard J. Honeywell, Carolien H. Smorenburg, Hans J. van der Vliet |
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| Přispěvatelé: | Medical oncology, Medical oncology laboratory, AGEM - Re-generation and cancer of the digestive system, CCA - Cancer Treatment and quality of life |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Cancer Research medicine.medical_specialty Folic acid Esophageal Neoplasms Esophagogastric cancer Cmax Phases of clinical research Adenocarcinoma Toxicology Gastroenterology Deoxycytidine 03 medical and health sciences 0302 clinical medicine Stomach Neoplasms Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Clinical endpoint Humans Pharmacology (medical) Vitamin B12 Aged Pharmacology Cisplatin Aged 80 and over business.industry Drug Synergism Middle Aged medicine.disease Gemcitabine Vitamin B 12 030104 developmental biology Oncology 030220 oncology & carcinogenesis Toxicity Dietary Supplements Original Article Female business medicine.drug |
| Zdroj: | van Zweeden, A A, van Groeningen, C J, Honeywell, R J, Giovannetti, E, Ruijter, R, Smorenburg, C H, Giaccone, G, Verheul, H M W, Peters, G J & van der Vliet, H J 2018, ' Randomized phase 2 study of gemcitabine and cisplatin with or without vitamin supplementation in patients with advanced esophagogastric cancer ', Cancer Chemotherapy and Pharmacology, vol. 82, no. 1, pp. 39-48 . https://doi.org/10.1007/s00280-018-3588-6 Cancer Chemotherapy and Pharmacology Cancer Chemotherapy and Pharmacology, 82(1), 39-48. Springer Verlag |
| ISSN: | 0344-5704 |
| Popis: | PURPOSE: Preclinical research and prior clinical observations demonstrated reduced toxicity and suggested enhanced efficacy of cisplatin due to folic acid and vitamin B12 suppletion. In this randomized phase 2 trial, we evaluated the addition of folic acid and vitamin B12 to first-line palliative cisplatin and gemcitabine in patients with advanced esophagogastric cancer (AEGC).METHODS: Patients with AEGC were randomized to gemcitabine 1250 mg/m2 (i.v. days 1, 8) and cisplatin 80 mg/m2 (i.v. day 1) q 3 weeks with or without folic acid (450 µg/day p.o.) and vitamin B12 (1000 µg i.m. q 9 weeks). The primary endpoint was response rate (RR). Secondary endpoints included overall survival (OS), time to progression (TTP), toxicity, and exploratory biomarker analyses. Cisplatin sensitivity and intracellular platinum levels were determined in adenocarcinoma cell lines cultured under high and low folate conditions in vitro.RESULTS: Adenocarcinoma cells cultured in medium with high folate levels were more sensitive to cisplatin and this was associated with increased intracellular platinum levels. In the randomized phase 2 clinical trial, which ran from October 2004 to September 2013, treatment was initiated in 78 of 82 randomized pts, 39 in each study arm. The RR was similar; 42.1% for supplemented patients vs. 32.4% for unsupplemented patients; p = 0.4. Median OS and TTP were 10.0 and 5.9 months for supplemented vs. 7.7 and 5.4 months for unsupplemented patients (OS, p = 0.9; TTP, p = 0.9). Plasma homocysteine was lower in the supplemented group [n = 20, 6.9 ± 1.6 (mean ± standard error of mean, SEM) µM; vs. 12.5 ± 4.0 µM; p CONCLUSION: Folic acid and vitamin B12 supplementation do not improve the RR, PFS, or OS of cisplatin and gemcitabine in patients with AEGC. |
| Databáze: | OpenAIRE |
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