{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:05:06Z","timestamp":1790075106543,"version":"4.0.1"},"reference-count":48,"publisher":"Impact Journals, LLC","issue":"18","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncotarget"],"published-print":{"date-parts":[[2015,6,30]]},"DOI":"10.18632\/oncotarget.3793","type":"journal-article","created":{"date-parts":[[2015,9,15]],"date-time":"2015-09-15T06:30:39Z","timestamp":1442298639000},"page":"16735-16745","source":"Crossref","is-referenced-by-count":36,"title":["Addition of rapamycin and hydroxychloroquine to metronomic chemotherapy as a second line treatment results in high salvage rates for refractory metastatic solid tumors: a pilot safety and effectiveness analysis in a small patient cohort"],"prefix":"10.18632","volume":"6","author":[{"given":"Kwan-Hwa","family":"Chi","sequence":"first","affiliation":[{"name":"Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan"},{"name":"School of Medicine and Institute of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Ling","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Yen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mau-Shin","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-Jyh","family":"Kao","sequence":"additional","affiliation":[{"name":"Division of Chest Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"7892","published-online":{"date-parts":[[2015,4,12]]},"reference":[{"key":"1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00280-013-2125-x","article-title":"Metronomic chemotherapy for cancer treatment: a decade of clinical studies","volume":"72","author":"Marchetti","year":"2013","journal-title":"Cancer chemotherapy and pharmacology"},{"key":"2","doi-asserted-by":"crossref","first-page":"4143","DOI":"10.1182\/blood.V94.12.4143","article-title":"Antiangiogenesis is produced by nontoxic doses of vinblastine","volume":"94","author":"Dammacco","year":"1999","journal-title":"Blood"},{"key":"3","first-page":"7501","article-title":"Low-dose chemotherapy combined with an antiangiogenic drug reduces human glioma growth in vivo","volume":"61","author":"Bikfalvi","year":"2001","journal-title":"Cancer research"},{"key":"4","first-page":"8408","article-title":"Synergistic effect of metronomic dosing of cyclophosphamide combined with specific antitumor immunotherapy in a murine melanoma model","volume":"63","author":"Cerundolo","year":"2003","journal-title":"Cancer research"},{"key":"5","doi-asserted-by":"crossref","first-page":"4722","DOI":"10.1200\/JCO.2007.12.2440","article-title":"Bevacizumab plus irinotecan in recurrent glioblastoma multiforme","volume":"25","author":"Friedman","year":"2007","journal-title":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology"},{"key":"6","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3802\/jgo.2013.24.3.258","article-title":"The combination of intravenous bevacizumab and metronomic oral cyclophosphamide is an effective regimen for platinum-resistant recurrent ovarian cancer","volume":"24","author":"Neubauer","year":"2013","journal-title":"Journal of gynecologic oncology"},{"key":"7","doi-asserted-by":"crossref","first-page":"4899","DOI":"10.1200\/JCO.2008.17.4789","article-title":"Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer","volume":"26","author":"Colleoni","year":"2008","journal-title":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology"},{"key":"8","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1179\/joc.2008.20.5.632","article-title":"Bevacizumab in combination with metronomic chemotherapy in patients with anthracycline- and taxane-refractory breast cancer","volume":"20","author":"Diaz-Rubio","year":"2008","journal-title":"Journal of chemotherapy"},{"issue":"supply","key":"9","article-title":"Phase II study of metronomic chemotherapy (MC) with bevacizumab (B) in patients with advanced nonsquamous non-small cell lung cancer (NSNSCLC)","volume":"31","author":"Robert","year":"2013","journal-title":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology"},{"key":"10","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jhep.2010.01.035","article-title":"Phase II study of combining sorafenib with metronomic tegafur\/uracil for advanced hepatocellular carcinoma","volume":"53","author":"Cheng","year":"2010","journal-title":"Journal of hepatology"},{"key":"11","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1038\/bjc.2013.553","article-title":"A phase 1 trial of imatinib, bevacizumab, and metronomic cyclophosphamide in advanced colorectal cancer","volume":"109","author":"Tempero","year":"2013","journal-title":"British journal of cancer"},{"key":"12","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nature06639","article-title":"Autophagy fights disease through cellular self-digestion","volume":"451","author":"Klionsky","year":"2008","journal-title":"Nature"},{"key":"13","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1158\/1535-7163.MCT-11-0047","article-title":"The Role of Autophagy in Cancer: Therapeutic Implications","volume":"10","author":"Sinicrope","year":"2011","journal-title":"Molecular Cancer Therapeutics"},{"key":"14","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.4161\/auto.29231","article-title":"Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors","volume":"10","author":"Carew","year":"2014","journal-title":"Autophagy"},{"key":"15","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.4161\/auto.29119","article-title":"Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma","volume":"10","author":"Alavi","year":"2014","journal-title":"Autophagy"},{"key":"16","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.4161\/auto.29118","article-title":"Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma","volume":"10","author":"O'Dwyer","year":"2014","journal-title":"Autophagy"},{"key":"17","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.4161\/auto.29264","article-title":"Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed\/refractory myeloma","volume":"10","author":"Bradner","year":"2014","journal-title":"Autophagy"},{"key":"18","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.4161\/auto.28984","article-title":"A phase I\/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme","volume":"10","author":"Tan","year":"2014","journal-title":"Autophagy"},{"key":"19","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.4161\/auto.29428","article-title":"Outcome of early clinical trials of the combination of hydroxychloroquine with chemotherapy in cancer","volume":"10","author":"Gewirtz","year":"2014","journal-title":"Autophagy"},{"key":"20","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/annonc\/mdi113","article-title":"mTOR-targeted therapy of cancer with rapamycin derivatives","volume":"16","author":"Raymond","year":"2005","journal-title":"Annals of oncology : official journal of the European Society for Medical Oncology \/ ESMO"},{"key":"21","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1038\/bjc.2013.644","article-title":"Tumour hypoxia determines the potential of combining mTOR and autophagy inhibitors to treat mammary tumours","volume":"109","author":"Feron","year":"2013","journal-title":"British journal of cancer"},{"key":"22","doi-asserted-by":"crossref","first-page":"e55096","DOI":"10.1371\/journal.pone.0055096","article-title":"Coordinate autophagy and mTOR pathway inhibition enhances cell death in melanoma","volume":"8","author":"Mehnert","year":"2013","journal-title":"PloS one"},{"key":"23","first-page":"ra81","article-title":"Akt and autophagy cooperate to promote survival of drug-resistant glioma","volume":"3","author":"Weiss","year":"2010","journal-title":"Science signaling"},{"key":"24","doi-asserted-by":"crossref","first-page":"e41831","DOI":"10.1371\/journal.pone.0041831","article-title":"Autophagy Suppresses RIP Kinase-Dependent Necrosis Enabling Survival to mTOR Inhibition","volume":"7","author":"White","year":"2012","journal-title":"PLoS ONE"},{"issue":"8 Supplement","key":"25","first-page":"5611","article-title":"Abstract 5611: A synthetic lethality combination with chloroquine and rapamycin on chemosensitization","volume":"72","author":"Chi","year":"2012","journal-title":"Cancer research"},{"key":"26","doi-asserted-by":"crossref","first-page":"e79658","DOI":"10.1371\/journal.pone.0079658","article-title":"The Synergistic Effect of Everolimus and Chloroquine on Endothelial Cell Number Reduction Is Paralleled by Increased Apoptosis and Reduced Autophagy Occurrence","volume":"8","author":"Pantano","year":"2013","journal-title":"PLoS ONE"},{"key":"27","unstructured":"Cancer Therapy Evaluation Program. NCI. Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Data files and Related Documents. http:\/\/evsncinihgov\/ftp1\/CTCAE\/Abouthtml. 2011. Accessed October 21."},{"key":"28","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Verweij","year":"2009","journal-title":"Eur J Cancer"},{"key":"29","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1055\/s-0030-1247132","article-title":"Modified RECIST (mRECIST) assessment for hepatocellular carcinoma","volume":"30","author":"Llovet","year":"2010","journal-title":"Seminars in liver disease"},{"key":"30","first-page":"6938","article-title":"Protracted low-dose effects on human endothelial cell proliferation and survival in vitro reveal a selective antiangiogenic window for various chemotherapeutic drugs","volume":"62","author":"Kerbel","year":"2002","journal-title":"Cancer research"},{"key":"31","first-page":"4342","article-title":"Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells","volume":"63","author":"Kerbel","year":"2003","journal-title":"Cancer research"},{"key":"32","first-page":"221","article-title":"Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts","volume":"8","author":"Kerbel","year":"2002","journal-title":"Clinical cancer research : an official journal of the American Association for Cancer Research"},{"key":"33","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nm0202-128","article-title":"Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor","volume":"8","author":"Geissler","year":"2002","journal-title":"Nature medicine"},{"key":"34","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ccr.2014.06.025","article-title":"Tumor vessel normalization by chloroquine independent of autophagy","volume":"26","author":"Boulanger","year":"2014","journal-title":"Cancer cell"},{"key":"35","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1200\/JCO.2006.07.3049","article-title":"Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria","volume":"25","author":"Benjamin","year":"2007","journal-title":"J Clin Oncol"},{"key":"36","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1007\/s10637-011-9775-5","article-title":"A phase I study of temozolomide and everolimus (RAD001) in patients with newly diagnosed and progressive glioblastoma either receiving or not receiving enzyme-inducing anticonvulsants: an NCIC CTG study","volume":"30","author":"Eisenhauer","year":"2012","journal-title":"Investigational new drugs"},{"key":"37","doi-asserted-by":"crossref","first-page":"337","DOI":"10.7326\/0003-4819-144-5-200603070-00008","article-title":"Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial","volume":"144","author":"Lopez-Gonzalez","year":"2006","journal-title":"Annals of internal medicine"},{"key":"38","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1007\/s10637-013-0015-z","article-title":"A phase I study of everolimus and CHOP in newly diagnosed peripheral T-cell lymphomas","volume":"31","author":"Kim","year":"2013","journal-title":"Investigational new drugs"},{"key":"39","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.ejca.2012.03.022","article-title":"Results of a phase II study of sirolimus and cyclophosphamide in patients with advanced sarcoma","volume":"48","author":"Baker","year":"2012","journal-title":"European journal of cancer"},{"key":"40","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/S1470-2045(14)70138-X","article-title":"Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial","volume":"15","author":"White","year":"2014","journal-title":"The Lancet Oncology"},{"key":"41","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1097\/JTO.0b013e318262de4a","article-title":"A phase I study of erlotinib and hydroxychloroquine in advanced non-small-cell lung cancer","volume":"7","author":"Sequist","year":"2012","journal-title":"Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer"},{"key":"42","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1038\/bjc.2013.467","article-title":"A phase-1b study of everolimus plus paclitaxel in patients with small-cell lung cancer","volume":"109","author":"Park","year":"2013","journal-title":"British journal of cancer"},{"key":"43","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/cam4.77","article-title":"Phase I study of everolimus and mitomycin C for patients with metastatic esophagogastric adenocarcinoma","volume":"2","author":"Al-Batran","year":"2013","journal-title":"Cancer medicine"},{"key":"44","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1002\/cncr.27986","article-title":"A phase 1 study of everolimus plus docetaxel plus cisplatin as induction chemotherapy for patients with locally and\/or regionally advanced head and neck cancer","volume":"119","author":"Pfister","year":"2013","journal-title":"Cancer"},{"key":"45","first-page":"35","article-title":"Pharmacotherapy options in rheumatoid arthritis","volume":"6","author":"Banik","year":"2013","journal-title":"Clin Med Insights Arthritis Musculoskelet Disord"},{"key":"46","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1097\/00007890-200101270-00019","article-title":"A worldwide, phase III, randomized, controlled, safety and efficacy study of a sirolimus\/cyclosporine regimen for prevention of acute rejection in recipients of primary mismatched renal allografts","volume":"71","author":"MacDonald","year":"2001","journal-title":"Transplantation"},{"key":"47","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1056\/NEJMoa1100391","article-title":"Efficacy and safety of sirolimus in lymphangioleiomyomatosis","volume":"364","author":"Downey","year":"2011","journal-title":"N Engl J Med"},{"key":"48","doi-asserted-by":"crossref","first-page":"4297","DOI":"10.4161\/cc.9.21.13817","article-title":"The autophagic tumor stroma model of cancer or \u201cbattery-operated tumor growth\u201d: A simple solution to the autophagy paradox","volume":"9","author":"Caro","year":"2010","journal-title":"Cell Cycle"}],"container-title":["Oncotarget"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.oncotarget.com\/lookup\/doi\/10.18632\/oncotarget.3793","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T11:55:12Z","timestamp":1589370912000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.oncotarget.com\/lookup\/doi\/10.18632\/oncotarget.3793"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,12]]},"references-count":48,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2015,6,30]]}},"alternative-id":["3793","25944689"],"URL":"https:\/\/doi.org\/10.18632\/oncotarget.3793","relation":{},"ISSN":["1949-2553"],"issn-type":[{"value":"1949-2553","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,12]]}}}