2026-04-17T02:45:42Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2229842025-12-05T00:08:34Zcom_2072_1057col_2072_478916col_2072_478917

urn:hdl:2445/222984 Effect of tumor-treating fields plus maintenance Temozolomide vs maintenance Temozolomide alone on survival in patients with glioblastoma Stupp, Roger Taillibert, Sophie Kanner, Andrew Read, William Steinberg, David M. Lhermitte, Benoit Toms, Steven Idbaih, Ahmed Ahluwalia, Manmeet S. Fink, Karen Meco, Francesco di Lieberman, Frank Zhu, Jay Jiguang Stragliotto, Giuseppe Tran, David D. Brem, Steven Hottinger, Andreas F. Kirson, Eilon D. Lavy Shahaf, Gitit Weinberg, Uri Kim, Chae Yong Paek, Sun Ha Nicholas, Garth Bruna, Jordi Hirte, Hal Weller, Michael Palti, Yoram Hegi, Monika E. Ram, Zvi Glioma Medicaments antineoplàstics Tumors cerebrals Gliomas Antineoplastic agents Brain tumors This trial assessed the efficacy of MR309 (a novel selective sigma-1 receptor ligand previously developed as E-52862) in ameliorating oxaliplatin-induced peripheral neuropathy (oxaipn). A discontinuous regimen of MR309 (400 mg/day, 5 days per cycle) was tested in patients with colorectal cancer receiving FOLFOX in a phase II, randomized, double-blind, placebo-controlled, multicenter clinical trial. Outcome measures included changes in 24-week quantitative measures of thermal sensitivity and total neuropathy score. In total, 124 patients were randomized (1:1) to MR309 or placebo. Sixty-three (50.8%) patients withdrew prematurely before completing 12 planned oxaliplatin cycles. Premature withdrawal because of cancer progression was less frequent in the MR309 group (7.4% vs 25.0% with placebo; p = 0.054). MR309 significantly reduced cold pain threshold temperature [mean treatment effect difference (SE) vs placebo: 5.29 (1.60)degrees C; p = 0.001] and suprathreshold cold stimulus-evoked pain intensity [mean treatment effect difference: 1.24 (0.57) points; p = 0.032]. Total neuropathy score, health-related quality-of-life measures, and nerve-conduction parameters changed similarly in both arms, whereas the proportion of patients with severe chronic neuropathy (National Cancer Institute Common Terminology Criteria for Adverse Events >= 3) was significantly lower in the MR309 group (3.0% vs 18.2% with placebo; p = 0.046). The total amount of oxaliplatin delivered was greater in the active arm (1618.9 mg vs 1453.8 mg with placebo; p = 0.049). Overall, 19.0% of patients experienced at least 1 treatment-related adverse event (25.8% and 11.9% with MR309 and placebo, respectively). Intermittent treatment with MR309 was associated with reduced acute oxaipn and higher oxaliplatin exposure, and showed a potential neuroprotective role for chronic cumulative oxaipn. Furthermore, MR309 showed an acceptable safety profile. 2025-09-05T10:05:54Z 2025-09-05T10:05:54Z 2017-12-19 2025-08-29T12:35:34Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.1001/jama.2017.18718 JAMA, 2017, vol. 318, num. 23, p. 2306-2316 https://doi.org/10.1001/jama.2017.18718 (c) American Medical Association, 2017 info:eu-repo/semantics/openAccess American Medical Association (AMA) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))