{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T18:01:07Z","timestamp":1777917667637,"version":"3.51.4"},"reference-count":35,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2000,11,1]],"date-time":"2000-11-01T00:00:00Z","timestamp":973036800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Tumori"],"published-print":{"date-parts":[[2000,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      In a phase II study, topotecan was evaluated for response and toxicity in patients with advanced pancreatic carcinoma at the schedule of 0.7 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/day q 21 days q 28 days.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Responses were assessed after at least 2 courses using WHO criteria, and toxicity was evaluated after each course according to the CTC-NCI standards. Between December 1995 and September 1997, 15 assessable patients (median age, 55 years; range, 36-74; median ECOG performance, 1; range, 0-3) were included in the study. All had biopsy-proven and measurable disease, a life-expectancy of at least 3 months, and normal bone marrow, liver, and renal function. None of the patients had undergone prior cytotoxic or radiation therapy, and 10 were initially treated by surgery. Twenty-five cycles were assessable for toxicity. Plasma was collected from 7 patients who had received a total of 10 cycles and was, after extraction with methanol at \u221220\u00b0C, analyzed for total topotecan by an HPLC method. The thus determined steady-state concentrations were assessed for their capacity to affect growth and DNA integrity in the BxPC-3 human pancreatic carcinoma cell line after 21 days of continuous exposure. For these purposes, we used a sulforhodamine B staining assay, and agarose gel electrophoresis, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Grades 3-4 leukopenia, thrombocytopenia, granulocytopenia, and anemia occurred in 8, 6, 8 and 8 cycles, respectively. Other mild to moderate side effects (grades 1-2) included malaise, nausea and vomiting, anorexia, and alopecia. No objective tumor response was documented. HPLC analysis of patients' plasma showed the attainment of constant steady-state levels of 1.0 \u00b1 0.1 ng\/mL during the entire infusion period. At such a concentration, topotecan did not significantly affect growth or DNA integrity in the BxPC-3 cells. Fifty percent cell growth inhibition and appreciable oligonucleosomal DNA fragmentation were only evident with 21 days topotecan \u2265 50 ng\/mL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our data suggest that the lack of clinical activity of 0.7 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      daily topotecan for 21 days q 28 days in patients with advanced pancreatic carcinoma might be partially attributed to the achievement of non-tumoricidal plasma drug concentrations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/030089160008600605","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T05:46:41Z","timestamp":1523944001000},"page":"458-464","source":"Crossref","is-referenced-by-count":1,"title":["Cellular and Clinical Pharmacokinetic\/Pharmacodynamic Basis for Lack of Efficacy of 21-Day Continuous Topotecan in Patients with Untreated Advanced Adenocarcinoma of the Pancreas"],"prefix":"10.1177","volume":"86","author":[{"given":"Dennis Ricardo","family":"August Mans","sequence":"first","affiliation":[{"name":"South-American Office for Anticancer Drug Development (SOAD), Lutheran University of Brazil, Canoas, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciane","family":"Di Leone","sequence":"additional","affiliation":[{"name":"South-American Office for Anticancer Drug Development (SOAD), Lutheran University of Brazil, Canoas, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paula","family":"Ferrary Caldas","sequence":"additional","affiliation":[{"name":"South-American Office for Anticancer Drug Development (SOAD), Lutheran University of Brazil, Canoas, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo","family":"Maino","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Almeida","sequence":"additional","affiliation":[{"name":"South-American Office for Anticancer Drug Development (SOAD), Lutheran University of Brazil, Canoas, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Isabel","family":"Cancela","sequence":"additional","affiliation":[{"name":"South-American Office for Anticancer Drug Development (SOAD), Lutheran University of Brazil, Canoas, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Grivicich","sequence":"additional","affiliation":[{"name":"South-American Office for Anticancer Drug Development (SOAD), Lutheran University of Brazil, Canoas, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana Brondani","family":"da Rocha","sequence":"additional","affiliation":[{"name":"South-American Office for Anticancer Drug Development (SOAD), Lutheran University of Brazil, Canoas, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilberto","family":"Schwartsmann","sequence":"additional","affiliation":[{"name":"South-American Office for Anticancer Drug Development (SOAD), Lutheran University of Brazil, Canoas, Brazil"},{"name":"Department of Medical Oncology, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2000,11,1]]},"reference":[{"key":"bibr1-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1016\/0731-7085(90)80122-6"},{"key":"bibr2-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107362"},{"key":"bibr3-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1996.14.12.3056"},{"key":"bibr4-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1996.14.9.2540"},{"key":"bibr5-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1991.9.3.365"},{"key":"bibr6-030089160008600605","first-page":"1054","volume-title":"In: Cancer: principles and practice of oncology","author":"Evans D.B.","year":"1997"},{"key":"bibr7-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600810718"},{"key":"bibr8-030089160008600605","first-page":"1325","volume":"29","author":"Frei E.","year":"1969","journal-title":"Cancer Res."},{"key":"bibr9-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(61)90060-1"},{"key":"bibr10-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.3.553"},{"key":"bibr11-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1007\/BF00686188"},{"key":"bibr12-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1007\/BF00685553"},{"key":"bibr13-030089160008600605","first-page":"1722","volume":"48","author":"Hsiang Y.-H.","year":"1988","journal-title":"Cancer Res."},{"key":"bibr14-030089160008600605","first-page":"1391","volume":"64","author":"Jeffrey I.S.","year":"1980","journal-title":"Cancer Treat. Rep."},{"key":"bibr15-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1021\/jm00105a017"},{"key":"bibr16-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1996.14.5.1552"},{"key":"bibr17-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.10.3302"},{"key":"bibr18-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.12.2743"},{"key":"bibr19-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/83.11.757"},{"key":"bibr20-030089160008600605","first-page":"A1615","volume":"14","author":"Nagourney R.A.","year":"1995","journal-title":"Proc. Am. Soc. Clin. Oncol."},{"key":"bibr21-030089160008600605","volume-title":"Guidelines for reporting of adverse drug reactions.","author":"National Cancer Institute:","year":"1988"},{"key":"bibr22-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1097\/00001813-199606000-00006"},{"key":"bibr23-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1996.14.10.2785"},{"key":"bibr24-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1996.14.4.1224"},{"key":"bibr25-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1007\/BF00873143"},{"key":"bibr26-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1996.14.8.2345"},{"key":"bibr27-030089160008600605","first-page":"220","volume":"23","author":"Schnall S.F.","year":"1996","journal-title":"Semin. Oncol."},{"key":"bibr28-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1989.7.9.1333"},{"key":"bibr29-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.9.1946"},{"key":"bibr30-030089160008600605","first-page":"A686","volume":"13","author":"Sugarman S.M.","year":"1994","journal-title":"Proc. Am. Soc. Clin. Oncol."},{"key":"bibr31-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.annonc.a058623"},{"key":"bibr32-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1021\/ja00968a057"},{"key":"bibr33-030089160008600605","first-page":"8","volume":"45","author":"Wingo P.A.","journal-title":"Clin."},{"key":"bibr34-030089160008600605","volume-title":"WHO handbook for reporting results of cancer treatment.","author":"World Health Organization","year":"1979"},{"key":"bibr35-030089160008600605","doi-asserted-by":"publisher","DOI":"10.1038\/284555a0"}],"container-title":["Tumori Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/030089160008600605","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/030089160008600605","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:20:00Z","timestamp":1777659600000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/030089160008600605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,11]]},"references-count":35,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2000,11]]}},"alternative-id":["10.1177\/030089160008600605"],"URL":"https:\/\/doi.org\/10.1177\/030089160008600605","relation":{},"ISSN":["0300-8916","2038-2529"],"issn-type":[{"value":"0300-8916","type":"print"},{"value":"2038-2529","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,11]]}}}