{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:13:03Z","timestamp":1793146383410,"version":"4.5.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>In older patients, esophageal squamous cell carcinoma (ESCC) is difficult to treat using standard therapies, including surgery and cisplatin-based chemoradiotherapy. Paclitaxel (PTX) has radiosensitizing activity. We conducted a phase I trial of PTX combined with radiotherapy to establish a standard therapy for locally advanced ESCC in older patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Enrollment was conducted at six centers in Japan from April 2016 to September 2019. The participants were aged\u2009\u2265\u200970\u00a0years, had locally advanced ESCC, and were intolerant to surgery or unwilling. A fixed 60-Gy radiation dose was administered in 30 fractions. PTX dosing levels started at 30\u00a0mg\/m<jats:sup>2<\/jats:sup> weekly for 6\u00a0weeks. Depending on the number of DLTs, the dose was set to be increased by 10\u00a0mg\/m<jats:sup>2<\/jats:sup> or switched to biweekly. A geriatric assessment was performed before treatment using the Geriatric-8 screening tool. The primary endpoint was dose-limiting toxicity (DLT).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We enrolled 24 patients (6 per group); DLT was observed in one (grade 4 hypokalemia), one (grade 3 aspiration), two (grade 3 radiodermatitis, grade 3 esophageal hemorrhage), and two (grade 3 anorexia, grade 5 pneumonitis) patients in the weekly PTX 30, 40, 50, and 60\u00a0mg\/m<jats:sup>2<\/jats:sup> groups, respectively. All adverse events, except death in the 60\u00a0mg\/m<jats:sup>2<\/jats:sup> group, showed reversible improvement, and the safety profile was considered acceptable. The 2-year survival and complete response rates were 40.0% and 54.2%, respectively. There was a significant difference in survival between favorable and unfavorable Geriatric-8 scores.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The recommended PTX dose with concomitant radiation was determined to be 50\u00a0mg\/m<jats:sup>2<\/jats:sup> weekly. Phase II trials at this dose are underway.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12885-024-12653-4","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T16:01:46Z","timestamp":1721404906000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Definitive chemoradiotherapy with paclitaxel for locally advanced esophageal squamous cell carcinoma in older patients (PARADISE-1): a phase I trial"],"prefix":"10.1186","volume":"24","author":[{"given":"Kenro","family":"Hirata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayo","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikatoshi","family":"Katada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Tsushima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiyo K.","family":"Imamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Tanigawara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Kitagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Hamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"key":"12653_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10388-021-00879-1","volume":"19","author":"M Watanabe","year":"2022","unstructured":"Watanabe M, Toh Y, Ishihara R, Kono K, Matsubara H, Murakami K, et al. Comprehensive registry of esophageal cancer in Japan, 2014. Esophagus. 2022;19:1\u201326. https:\/\/doi.org\/10.1007\/s10388-021-00879-1.","journal-title":"Esophagus"},{"key":"12653_CR2","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1200\/JCO.2022.40.4_suppl","volume":"40","author":"K Kato","year":"2022","unstructured":"Kato K, Ito Y, Daiko H, Ozawa S, Ogata T, Hara H, et al. A randomized controlled phase III trial comparing two chemotherapy regimen and chemoradiotherapy regimen as neoadjuvant treatment for locally advanced esophageal cancer, JCOG1109 NExT study. J Clin Oncol. 2022;40:238. https:\/\/doi.org\/10.1200\/JCO.2022.40.4_suppl.","journal-title":"J Clin Oncol"},{"key":"12653_CR3","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1056\/NEJMoa1112088","volume":"366","author":"P van Hagen","year":"2012","unstructured":"van Hagen P, Hulshof MCCM, van Lanschot JJB, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BPL, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074\u201384. https:\/\/doi.org\/10.1056\/NEJMoa1112088.","journal-title":"N Engl J Med"},{"key":"12653_CR4","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.ijrobp.2022.07.007","volume":"114","author":"H Takeuchi","year":"2022","unstructured":"Takeuchi H, Ito Y, Machida R, Kato K, Onozawa M, Minashi K, et al. A single-arm confirmatory study of definitive chemoradiation therapy including salvage treatment for clinical stage II\/III esophageal squamous cell carcinoma (JCOG0909 study). Int J Radiat Oncol Biol Phys. 2022;114:454\u201362. https:\/\/doi.org\/10.1016\/j.ijrobp.2022.07.007.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"12653_CR5","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1111\/j.1442-2050.2012.01353.x","volume":"26","author":"SR Markar","year":"2013","unstructured":"Markar SR, Karthikesalingam A, Thrumurthy S, Ho A, Muallem G, Low DE. Systematic review and pooled analysis assessing the association between elderly age and outcome following surgical resection of esophageal malignancy: Elderly esophagectomy. Dis Esophagus. 2013;26:250\u201362. https:\/\/doi.org\/10.1111\/j.1442-2050.2012.01353.x.","journal-title":"Dis Esophagus"},{"key":"12653_CR6","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1093\/icvts\/ivz208","volume":"29","author":"Y Han","year":"2019","unstructured":"Han Y, Liu S, Guo W, Zhang Y, Li H. Clinical outcomes of oesophagectomy in elderly versus relatively younger patients: a meta-analysis. Interact Cardiovasc Thorac Surg. 2019;29:897\u2013905. https:\/\/doi.org\/10.1093\/icvts\/ivz208.","journal-title":"Interact Cardiovasc Thorac Surg"},{"key":"12653_CR7","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1245\/s10434-020-09072-7","volume":"28","author":"E Booka","year":"2021","unstructured":"Booka E, Haneda R, Ishii K, Tsushima T, Yasui H, Tsubosa Y. The negative impact of preoperative chemotherapy on survival after esophagectomy for vulnerable elderly patients with esophageal cancer. Ann Surg Oncol. 2021;28:1786\u201395. https:\/\/doi.org\/10.1245\/s10434-020-09072-7.","journal-title":"Ann Surg Oncol"},{"key":"12653_CR8","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s10388-018-0605-0","volume":"15","author":"Y Hamamoto","year":"2018","unstructured":"Hamamoto Y, Sakakibara N, Nagashima F, Kitagawa Y, Higashi T. Treatment selection for esophageal cancer: evaluation from a nationwide database. Esophagus. 2018;15:109\u201314. https:\/\/doi.org\/10.1007\/s10388-018-0605-0.","journal-title":"Esophagus"},{"key":"12653_CR9","doi-asserted-by":"publisher","first-page":"1878","DOI":"10.1053\/j.gastro.2021.08.007","volume":"161","author":"K Kato","year":"2021","unstructured":"Kato K, Ito Y, Nozaki I, Daiko H, Kojima T, Yano M, et al. Parallel-group controlled trial of surgery versus chemoradiotherapy in patients with stage I esophageal squamous cell carcinoma. Gastroenterology. 2021;161:1878-86.e2. https:\/\/doi.org\/10.1053\/j.gastro.2021.08.007.","journal-title":"Gastroenterology"},{"key":"12653_CR10","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.adro.2016.07.002","volume":"1","author":"A Ohba","year":"2016","unstructured":"Ohba A, Kato K, Ito Y, Katada C, Ishiyama H, Yamamoto S, et al. Chemoradiation therapy with docetaxel in elderly patients with stage II\/III esophageal cancer: a phase 2 trial. Adv Radiat Oncol. 2016;1:230\u20136. https:\/\/doi.org\/10.1016\/j.adro.2016.07.002.","journal-title":"Adv Radiat Oncol."},{"key":"12653_CR11","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1093\/jjco\/hyv183","volume":"46","author":"Y Hamamoto","year":"2016","unstructured":"Hamamoto Y, Akutsu Y, Nagashima F, Hironaka S, Ito Y, Kato K, et al. Multicenter questionnaire survey on patterns of care for elderly patients with esophageal squamous cell carcinoma by the Japan Esophageal Oncology Group. Jpn J Clin Oncol. 2016;46:111\u20135. https:\/\/doi.org\/10.1093\/jjco\/hyv183.","journal-title":"Jpn J Clin Oncol"},{"key":"12653_CR12","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1093\/jjco\/hyac067","volume":"52","author":"Y Hamamoto","year":"2022","unstructured":"Hamamoto Y, Murakami K, Kato K, Kitagawa Y. Management of elderly patients with esophageal squamous cell cancer. Jpn J Clin Oncol. 2022;52:816\u201324. https:\/\/doi.org\/10.1093\/jjco\/hyac067.","journal-title":"Jpn J Clin Oncol"},{"key":"12653_CR13","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1016\/j.ijrobp.2005.09.027","volume":"64","author":"M Kawashima","year":"2006","unstructured":"Kawashima M, Kagami Y, Toita T, Uno T, Sugiyama M, Tamura Y, et al. Prospective trial of radiotherapy for patients 80 years of age or older with squamous cell carcinoma of the thoracic esophagus. Int J Radiat Oncol Biol Phys. 2006;64:1112\u201321. https:\/\/doi.org\/10.1016\/j.ijrobp.2005.09.027.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"12653_CR14","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1007\/s00280-010-1422-x","volume":"67","author":"K Kato","year":"2011","unstructured":"Kato K, Tahara M, Hironaka S, Muro K, Takiuchi H, Hamamoto Y, et al. A phase II study of paclitaxel by weekly 1-h infusion for advanced or recurrent esophageal cancer in patients who had previously received platinum-based chemotherapy. Cancer Chemother Pharmacol. 2011;67:1265\u201372. https:\/\/doi.org\/10.1007\/s00280-010-1422-x.","journal-title":"Cancer Chemother Pharmacol"},{"key":"12653_CR15","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/0360-3016(94)90456-1","volume":"29","author":"J Liebmann","year":"1994","unstructured":"Liebmann J, Cook JA, Fisher J, Teague D, Mitchell JB. Changes in radiation survival curve parameters in human tumor and rodent cells exposed to paclitaxel (Taxol). Int J Radiat Oncol Biol Phys. 1994;29:559\u201364. https:\/\/doi.org\/10.1016\/0360-3016(94)90456-1.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"12653_CR16","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/0360-3016(92)90888-o","volume":"22","author":"RB Tishler","year":"1992","unstructured":"Tishler RB, Schiff PB, Geard CR, Hall EJ. Taxol: a novel radiation sensitizer. Int J Radiat Oncol Biol Phys. 1992;22:613\u20137. https:\/\/doi.org\/10.1016\/0360-3016(92)90888-o.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"12653_CR17","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1093\/jnci\/86.6.441","volume":"86","author":"J Liebmann","year":"1994","unstructured":"Liebmann J, Cook JA, Fisher J, Teague D, Mitchell JB. In vitro studies of Taxol as a radiation sensitizer in human tumor cells. J Natl Cancer Inst. 1994;86:441\u20136. https:\/\/doi.org\/10.1093\/jnci\/86.6.441.","journal-title":"J Natl Cancer Inst"},{"key":"12653_CR18","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1200\/JCO.1996.14.4.1071","volume":"14","author":"B Reckzeh","year":"1996","unstructured":"Reckzeh B, Merte H, Pfl\u00fcger KH, Pfab R, Wolf M, Havemann K. Severe lymphocytopenia and interstitial pneumonia in patients treated with paclitaxel and simultaneous radiotherapy for non-small-cell lung cancer. J Clin Oncol. 1996;14:1071\u20136. https:\/\/doi.org\/10.1200\/JCO.1996.14.4.1071.","journal-title":"J Clin Oncol"},{"key":"12653_CR19","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s10388-016-0556-2","volume":"14","author":"Japan Esophageal Society","year":"2017","unstructured":"Japan Esophageal Society. Japanese classification of esophageal cancer, 11th edition: part II and III. Esophagus. 2017;14:37\u201365 https:\/\/doi.org\/10.1007%2Fs10388-016-0556-2 .","journal-title":"Esophagus"},{"key":"12653_CR20","doi-asserted-by":"publisher","first-page":"2166","DOI":"10.1093\/annonc\/mdr587","volume":"23","author":"CA Bellera","year":"2012","unstructured":"Bellera CA, Rainfray M, Mathoulin-P\u00e9lissier S, Mertens C, Delva F, Fonck M, et al. Screening older cancer patients: first evaluation of the G-8 geriatric screening tool. Ann Oncol. 2012;23:2166\u201372. https:\/\/doi.org\/10.1093\/annonc\/mdr587.","journal-title":"Ann Oncol"},{"key":"12653_CR21","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1093\/geront\/9.3_Part_1.179","volume":"9","author":"MP Lawton","year":"1969","unstructured":"Lawton MP, Brody EM. Assessment of older people: Self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9:179\u201386. https:\/\/doi.org\/10.1093\/geront\/9.3_Part_1.179.","journal-title":"Gerontologist"},{"key":"12653_CR22","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","volume":"40","author":"ME Charlson","year":"1987","unstructured":"Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373\u201383. https:\/\/doi.org\/10.1016\/0021-9681(87)90171-8.","journal-title":"J Chronic Dis"},{"key":"12653_CR23","doi-asserted-by":"publisher","first-page":"2416","DOI":"10.1111\/bcp.13354","volume":"83","author":"H Kenmotsu","year":"2017","unstructured":"Kenmotsu H, Imamura CK, Ono A, Omori S, Nakashima K, Wakuda K, et al. The effects of advanced age and serum \u03b11 -acid glycoprotein on docetaxel unbound exposure and dose-limiting toxicity in cancer patients. Br J Clin Pharmacol. 2017;83:2416\u201325. https:\/\/doi.org\/10.1111\/bcp.13354.","journal-title":"Br J Clin Pharmacol"},{"key":"12653_CR24","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1002\/jps.24064","volume":"103","author":"K Vanstraelen","year":"2014","unstructured":"Vanstraelen K, Wauters J, De Loor H, Vercammen I, Annaert P, Lagrou K, et al. Protein-binding characteristics of voriconazole determined by high-throughput equilibrium dialysis. J Pharm Sci. 2014;103:2565\u201370. https:\/\/doi.org\/10.1002\/jps.24064.","journal-title":"J Pharm Sci"},{"key":"12653_CR25","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1097\/COC.0b013e3180ca7c84","volume":"30","author":"S Takeuchi","year":"2007","unstructured":"Takeuchi S, Ohtsu A, Doi T, Kojima T, Minashi K, Mera K, et al. A retrospective study of definitive chemoradiotherapy for elderly patients with esophageal cancer. Am J Clin Oncol. 2007;30:607\u201311. https:\/\/doi.org\/10.1097\/COC.0b013e3180ca7c84.","journal-title":"Am J Clin Oncol."},{"key":"12653_CR26","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1111\/j.1442-2050.2010.01062.x","volume":"23","author":"R Wakui","year":"2010","unstructured":"Wakui R, Yamashita H, Okuma K, Kobayashi S, Shiraishi K, Terahara A, et al. Esophageal cancer: definitive chemoradiotherapy for elderly patients: CRT for elderly with esophageal cancer. Dis Esophagus. 2010;23:572\u20139. https:\/\/doi.org\/10.1111\/j.1442-2050.2010.01062.x.","journal-title":"Dis Esophagus"},{"key":"12653_CR27","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1038\/sj.bjc.6604749","volume":"99","author":"D Tougeron","year":"2008","unstructured":"Tougeron D, Di Fiore F, Thureau S, Berbera N, Iwanicki-Caron I, Hamidou H, et al. Safety and outcome of definitive chemoradiotherapy in elderly patients with oesophageal cancer. Br J Cancer. 2008;99:1586\u201392. https:\/\/doi.org\/10.1038\/sj.bjc.6604749.","journal-title":"Br J Cancer"},{"key":"12653_CR28","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/s13014-018-1044-8","volume":"13","author":"F Walter","year":"2018","unstructured":"Walter F, B\u00f6ckle D, Schmidt-Hegemann N-S, K\u00f6pple R, Gerum S, Boeck S, et al. Clinical outcome of elderly patients (\u2265 70 years) with esophageal cancer undergoing definitive or neoadjuvant radio(chemo)therapy: a retrospective single center analysis. Radiat Oncol. 2018;13:93. https:\/\/doi.org\/10.1186\/s13014-018-1044-8.","journal-title":"Radiat Oncol"},{"key":"12653_CR29","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1001\/jamaoncol.2021.2705","volume":"7","author":"Y Ji","year":"2021","unstructured":"Ji Y, Du X, Zhu W, Yang Y, Ma J, Zhang L, et al. Efficacy of concurrent chemoradiotherapy with S-1 vs radiotherapy alone for older patients with esophageal cancer: a multicenter randomized phase 3 clinical trial. JAMA Oncol. 2021;7:1459\u201366. https:\/\/doi.org\/10.1001\/jamaoncol.2021.2705.","journal-title":"JAMA Oncol"},{"key":"12653_CR30","doi-asserted-by":"publisher","first-page":"e405","DOI":"10.1016\/j.cllc.2020.06.004","volume":"22","author":"A-L Couderc","year":"2021","unstructured":"Couderc A-L, Tomasini P, Nouguer\u00e8de E, Rey D, Correard F, Montegut C, et al. Older patients treated for lung and thoracic cancers: unplanned hospitalizations and overall survival. Clin Lung Cancer. 2021;22:e405\u201314. https:\/\/doi.org\/10.1016\/j.cllc.2020.06.004.","journal-title":"Clin Lung Cancer"},{"key":"12653_CR31","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1186\/s12885-015-1800-1","volume":"15","author":"L Pottel","year":"2015","unstructured":"Pottel L, Lycke M, Boterberg T, Pottel H, Goethals L, Duprez F, et al. G-8 indicates overall and quality-adjusted survival in older head and neck cancer patients treated with curative radiochemotherapy. BMC Cancer. 2015;15:875. https:\/\/doi.org\/10.1186\/s12885-015-1800-1.","journal-title":"BMC Cancer"},{"key":"12653_CR32","doi-asserted-by":"publisher","first-page":"e0179694","DOI":"10.1371\/journal.pone.0179694","volume":"12","author":"M Takahashi","year":"2017","unstructured":"Takahashi M, Takahashi M, Komine K, Yamada H, Kasahara Y, Chikamatsu S, et al.\u00a0The G8 screening tool enhances prognostic value to ECOG performance status in elderly cancer patients: a retrospective, single institutional study. PLoS ONE. 2017;12:e0179694.\u00a0https:\/\/doi.org\/10.1371\/journal.pone.0179694","journal-title":"PLoS ONE"},{"key":"12653_CR33","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1200\/JCO.1995.13.1.180","volume":"13","author":"L Gianni","year":"1995","unstructured":"Gianni L, Kearns CM, Giani A, Capri G, Vigan\u00f3 L, Lacatelli A, et al. Nonlinear pharmacokinetics and metabolism of paclitaxel and its pharmacokinetic\/pharmacodynamic relationships in humans. J Clin Oncol. 1995;13:180\u201390. https:\/\/doi.org\/10.1200\/JCO.1995.13.1.180.","journal-title":"J Clin Oncol"}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-024-12653-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12885-024-12653-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-024-12653-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T16:04:01Z","timestamp":1721405041000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccancer.biomedcentral.com\/articles\/10.1186\/s12885-024-12653-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,19]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["12653"],"URL":"https:\/\/doi.org\/10.1186\/s12885-024-12653-4","relation":{},"ISSN":["1471-2407"],"issn-type":[{"value":"1471-2407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,19]]},"assertion":[{"value":"21 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The current study was approved by the ethics committee of Keio University School of Medicine and the Certified Review Board of Keio (CRB3180017), and permission to conduct the study was obtained from the management of all participating facilities. In addition, written informed consent for participation was obtained from all participants. The study was performed in accordance with the relevant guidelines and regulations of the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Yasuo Hamamoto is an Associate Editor of this journal. The other authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"873"}}