{"corpus_id":7120096,"paper_sha":"a70990681e564df117b1161931bde173f80ad7b7","doi":"10.1038/sj.bjc.6602112","arxiv_id":null,"pmid":15292922,"pmcid":"2409873","mag_id":2012459525,"dblp_id":null,"acl_id":null,"title":"A phase I/II study of gemcitabine and fractionated cisplatin in an outpatient setting using a 21-day schedule in patients with advanced and metastatic bladder cancer","year":2004,"publication_date":"2004-08-03","venue":"British Journal of Cancer","journal":{"name":"British Journal of Cancer","pages":"844 - 849","volume":"91"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle","ClinicalTrial"],"pubmed_pub_types":["Clinical Trial","Clinical Trial, Phase I","Clinical Trial, Phase II","Journal Article"],"s2_fields_of_study":["Medicine"],"reference_count":18,"citation_count":108,"influential_citation_count":2,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Adult","mj":false,"ui":"D000328"},{"d":"Aged","mj":false,"ui":"D000368"},{"d":"Antineoplastic Agents","mj":false,"qs":[{"q":"adverse effects","mj":false,"ui":"Q000009"},{"q":"therapeutic use","mj":true,"ui":"Q000627"}],"ui":"D000970"},{"d":"Antineoplastic Combined Chemotherapy Protocols","mj":false,"ui":"D000971"},{"d":"Carcinoma, Transitional Cell","mj":false,"qs":[{"q":"drug therapy","mj":true,"ui":"Q000188"},{"q":"mortality","mj":false,"ui":"Q000401"},{"q":"secondary","mj":false,"ui":"Q000556"}],"ui":"D002295"},{"d":"Cisplatin","mj":false,"qs":[{"q":"administration & dosage","mj":true,"ui":"Q000008"},{"q":"adverse effects","mj":false,"ui":"Q000009"}],"ui":"D002945"},{"d":"Deoxycytidine","mj":false,"qs":[{"q":"administration & dosage","mj":true,"ui":"Q000008"},{"q":"adverse effects","mj":false,"ui":"Q000009"},{"q":"analogs & derivatives","mj":true,"ui":"Q000031"}],"ui":"D003841"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Kidney","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D007668"},{"d":"Kidney Function Tests","mj":false,"ui":"D007677"},{"d":"Lymphatic Metastasis","mj":false,"qs":[{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D008207"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Maximum Tolerated Dose","mj":true,"ui":"D020714"},{"d":"Middle Aged","mj":false,"ui":"D008875"},{"d":"Outpatients","mj":false,"ui":"D010045"},{"d":"Treatment Outcome","mj":false,"ui":"D016896"},{"d":"Urinary Bladder Neoplasms","mj":false,"qs":[{"q":"drug therapy","mj":true,"ui":"Q000188"},{"q":"mortality","mj":false,"ui":"Q000401"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D001749"},{"d":"Viscera","mj":false,"qs":[{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D014781"},{"d":"Gemcitabine","mj":false,"ui":"D000093542"}],"chemicals":[{"n":"Antineoplastic Agents","ui":"D000970","reg":"0"},{"n":"Deoxycytidine","ui":"D003841","reg":"0W860991D6"},{"n":"Cisplatin","ui":"D002945","reg":"Q20Q21Q62J"},{"n":"Gemcitabine","ui":"D000093542","reg":"0"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://www.nature.com/articles/6602112.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/a70990681e564df117b1161931bde173f80ad7b7","s2_open_access_license":"CCBYNCSA","s2_open_access_status":"HYBRID","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"A randomised phase III trial of MVAC (methotrexate, vincristine, doxorubicin, cisplatin) vs gemcitabine and cisplatin (GC) (G 1000 mg m−2 days 1, 8, and 15 plus C 70 mg m−2 day 2, q 4 wks) indicated GC had similar efficacy and lower toxicity (JCO 2000). Significant haematologic toxicities in the GC arm occurred on day 15, necessitating dose adjustments in 37% of cycles. We conducted a phase I/II dose escalation trial using GC on a 21-day cycle, with G and C split between days 1 and 8. The objective of the study to define maximum-tolerated dose and dose-limiting toxicity (DLT), objective response rate, and overall survival. In all, 32 patients with locally advanced, relapsed, or metastatic disease received: dose level 1, G/C 1000/35; level 2, 1100/35; level 3, 1200/35; level 4, 1200/45 mg m−2 (G and C given on days 1 and 8 every 3 wks). A total of 19 patients had glomerular filtration rate <60 ml min−1 and 19 patients had metastatic disease. Dose-limiting toxicity was haematologic (grade 4 thrombocytopenia) at dose level 2. Of 151 cycles, at day 15, platelets were <100 in 61 cycles; neutrophils <0.5, platelets <50 in 26 cycles. Only seven cycles were deferred due to haematological toxicity; four for renal toxicity (chemotherapy instituted posthydration). Overall response rate was 65.5% on an intention-to-treat analysis (75% [21/28] for assessable patients), with four complete responses (12.5%) and 17 partial responses (53%). After the median follow-up of 17.2 months (range 13.1–32.4 months), 12 patients remain alive. The overall median survival was 16 months (range 10.1–26.6 months). G plus C every 3 weeks is active and well tolerated in an outpatient setting, even in patients receiving prior platinum-based regimens and with poor renal reserve.","claims":[{"public_id":"cl_8a778e2ac9b78feeeb5fccfac255654b","status":"active","text":"Dose-limiting toxicity was haematologic, specifically grade 4 thrombocytopenia, at dose level 2.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_8a778e2ac9b78feeeb5fccfac255654b"},{"public_id":"cl_ee5b3ab32f15a5709ccb4acdab5d25ed","status":"active","text":"Gemcitabine and cisplatin given on a 21-day schedule in an outpatient setting is active and well tolerated in advanced bladder cancer.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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