{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T15:04:29Z","timestamp":1775747069053,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,12,28]],"date-time":"2015-12-28T00:00:00Z","timestamp":1451260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2016,3,15]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The type 3 Dearing reovirus (Reolysin) is a naturally occurring virus that preferentially infects and causes oncolysis in tumor cells with a <jats:italic>Ras<\/jats:italic>\u2010activated pathway. It induces host immunity and cell cycle arrest and acts synergistically with cytotoxic agents.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>This study evaluated Reolysin combined with paclitaxel and carboplatin in patients with metastatic\/recurrent KRAS\u2010mutated or epidermal growth factor receptor (EGFR)\u2013mutated\/amplified non\u2013small cell lung cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Thirty\u2010seven patients were treated. Molecular alterations included 20 KRAS mutations, 10 EGFR amplifications, 3 EGFR mutations, and 4 BRAF\u2010V600E mutations. In total, 242 cycles (median, 4; range, 1\u201047) were completed. The initial doses were area under the curve (AUC) 6\u2009mg\/mL\/min for carboplatin, 200\u2009mg\/m<jats:sup>2<\/jats:sup> for paclitaxel on day 1, and 3\u2009\u00d7\u200910<jats:sup>10<\/jats:sup> 50% tissue culture infective dose for Reolysin on days 1 to 5 of each 21\u2010day cycle. Because of diarrhea and febrile neutropenia (in the first 2 patients), subsequent doses were reduced to 175\u2009mg\/m<jats:sup>2<\/jats:sup> for paclitaxel and AUC 5\u2009mg\/mL\/min for carboplatin. Toxicities included fatigue, diarrhea, nausea\/vomiting, neutropenia, arthralgia\/myalgia, anorexia, and electrolyte abnormalities. Response Evaluation Criteria in Solid Tumors 1.0 responses included the following: partial response for 11 patients, stable disease (SD) for 20 patients, progressive disease for 4 patients, and not evaluable for 2 patients (objective response rate, 31%; 90% 1\u2010sided lower confidence interval, 21%). Four SD patients had &gt;40% positron emission tomography standardized uptake value reductions. The median progression\u2010free survival, median overall survival, and 12\u2010month overall survival rate were 4 months, 13.1 months, and 57%, respectively. Seven patients were alive after a median follow\u2010up of 34.2 months; they included 2 patients without disease progression at 37 and 50 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Reolysin in combination with paclitaxel and carboplatin was well tolerated. The observed response rate suggests a benefit of the reovirus for chemotherapy. A follow\u2010up randomized study is recommended. The proportion of patients surviving longer than 2 years (30%) suggests a second\/third\u2010line treatment effect or possibly the triggering of an immune response after tumor reovirus infiltration. <jats:bold><jats:italic>Cancer<\/jats:italic> 2016;122:875\u201383<\/jats:bold>. \u00a9 <jats:italic>2015 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.29856","type":"journal-article","created":{"date-parts":[[2015,12,28]],"date-time":"2015-12-28T09:28:46Z","timestamp":1451294926000},"page":"875-883","source":"Crossref","is-referenced-by-count":68,"title":["Oncolytic reovirus in combination with chemotherapy in metastatic or recurrent non\u2013small cell lung cancer patients with <scp>K<\/scp>RAS\u2010activated tumors"],"prefix":"10.1002","volume":"122","author":[{"given":"Miguel A.","family":"Villalona\u2010Calero","sequence":"first","affiliation":[{"name":"Division of Medical Oncology Department of Internal Medicine, Ohio State University 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