{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T03:38:38Z","timestamp":1775705918648,"version":"3.50.1"},"reference-count":18,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2000,12,15]]},"abstract":"<jats:p> PURPOSE: To define the maximum-tolerated dose, recommended phase II dose (RD), dose-limiting toxicity (DLT), and pharmacokinetics of a novel taxane, RPR 109881A, administered on days 1 and 8 of a 21-day cycle. <\/jats:p><jats:p> PATIENTS AND METHODS: Twenty-nine patients were enrolled and treated according to a modified continual reassessment method from a starting dose of 7.5 mg\/m<jats:sup>2<\/jats:sup> to 52.5 mg\/m<jats:sup>2<\/jats:sup>. Detailed pharmacokinetic analyses of blood and urine were performed on days 1 and 8 of the first cycle. Toxicity was monitored weekly. <\/jats:p><jats:p> RESULTS: DLT consisting of grade 3 or 4 diarrhea was seen in three of six patients at 52.5 mg\/m<jats:sup>2<\/jats:sup>. Grade 3 or 4 granulocytopenia was also seen in five of six patients treated at this dose (four of six in the first cycle). At the next lower dose level, 45 mg\/m<jats:sup>2<\/jats:sup> toxicity was moderate, with only one of 12 patients experiencing severe diarrhea and grade 4 granulocytopenia with associated infection. Drug concentrations were consistent with a three-compartment open model. The total-body clearance suggests a linear dose-concentration relationship. RPR 109881A has a high clearance (mean, 42.6 L\/h\/m<jats:sup>2<\/jats:sup>), a large volume of distribution (mean, 952 L\/m<jats:sup>2<\/jats:sup>), and a long terminal half-life (mean, 24 hours). There was no drug accumulation between days 1 and 8. One partial response was seen in a patient with renal cell carcinoma. <\/jats:p><jats:p> CONCLUSION: The RD of RPR 109881A given as a 1-hour infusion on days 1 and 8 of a 21-day cycle is 45 mg\/m<jats:sup>2<\/jats:sup>. At this dose the drug is well tolerated and should be further studied. <\/jats:p>","DOI":"10.1200\/jco.2000.18.24.4098","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T06:42:41Z","timestamp":1487918561000},"page":"4098-4108","source":"Crossref","is-referenced-by-count":45,"title":["Phase I Dose-Finding Study of a New Taxane, RPR 109881A, Administered as a One-Hour Intravenous Infusion Days 1 and 8 to Patients With Advanced Solid Tumors"],"prefix":"10.1200","volume":"18","author":[{"given":"Karen A.","family":"Gelmon","sequence":"first","affiliation":[{"name":"From the British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, British Columbia; L\u2019 Hotel Dieu du CHUM, Montreal, Quebec; and National Cancer Institute of Canada Clinical Trials Group, Queen\u2019s University, Kingston, Ontario, Canada; and Rh\u00f4ne-Poulenc Rorer, Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Latreille","sequence":"additional","affiliation":[{"name":"From the British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, British Columbia; L\u2019 Hotel Dieu du CHUM, Montreal, Quebec; and National Cancer Institute of Canada Clinical Trials Group, Queen\u2019s University, Kingston, Ontario, Canada; and Rh\u00f4ne-Poulenc Rorer, Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Tolcher","sequence":"additional","affiliation":[{"name":"From the British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, British Columbia; L\u2019 Hotel Dieu du CHUM, Montreal, Quebec; and National Cancer Institute of Canada Clinical Trials Group, Queen\u2019s University, Kingston, Ontario, Canada; and Rh\u00f4ne-Poulenc Rorer, Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc","family":"G\u00e9nier","sequence":"additional","affiliation":[{"name":"From the British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, British Columbia; L\u2019 Hotel Dieu du CHUM, Montreal, Quebec; and National Cancer Institute of Canada Clinical Trials Group, Queen\u2019s University, Kingston, Ontario, Canada; and Rh\u00f4ne-Poulenc Rorer, Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryn","family":"Fisher","sequence":"additional","affiliation":[{"name":"From the British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, British Columbia; L\u2019 Hotel Dieu du CHUM, Montreal, Quebec; and National Cancer Institute of Canada Clinical Trials Group, Queen\u2019s University, Kingston, Ontario, Canada; and Rh\u00f4ne-Poulenc Rorer, Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Forand","sequence":"additional","affiliation":[{"name":"From the British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, British Columbia; L\u2019 Hotel Dieu du CHUM, Montreal, Quebec; and National Cancer Institute of Canada Clinical Trials Group, Queen\u2019s University, Kingston, Ontario, Canada; and Rh\u00f4ne-Poulenc Rorer, Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"D\u2019Aloisio","sequence":"additional","affiliation":[{"name":"From the British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, British Columbia; L\u2019 Hotel Dieu du CHUM, Montreal, Quebec; and National Cancer Institute of Canada Clinical Trials Group, Queen\u2019s University, Kingston, Ontario, Canada; and Rh\u00f4ne-Poulenc Rorer, Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Vernillet","sequence":"additional","affiliation":[{"name":"From the British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, British Columbia; L\u2019 Hotel Dieu du CHUM, Montreal, Quebec; and National Cancer Institute of Canada Clinical Trials Group, Queen\u2019s University, Kingston, Ontario, Canada; and Rh\u00f4ne-Poulenc Rorer, Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc","family":"Daigneault","sequence":"additional","affiliation":[{"name":"From the British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, British Columbia; L\u2019 Hotel Dieu du CHUM, Montreal, Quebec; and National Cancer Institute of Canada Clinical Trials Group, Queen\u2019s University, Kingston, Ontario, Canada; and Rh\u00f4ne-Poulenc Rorer, Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann","family":"Lebecq","sequence":"additional","affiliation":[{"name":"From the British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, British Columbia; L\u2019 Hotel Dieu du CHUM, Montreal, Quebec; and National Cancer Institute of Canada Clinical Trials Group, Queen\u2019s University, Kingston, Ontario, Canada; and Rh\u00f4ne-Poulenc Rorer, Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Besenval","sequence":"additional","affiliation":[{"name":"From the British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, British Columbia; L\u2019 Hotel Dieu du CHUM, Montreal, Quebec; and National Cancer Institute of Canada Clinical Trials Group, Queen\u2019s University, Kingston, Ontario, Canada; and Rh\u00f4ne-Poulenc Rorer, Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Eisenhauer","sequence":"additional","affiliation":[{"name":"From the British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, British Columbia; L\u2019 Hotel Dieu du CHUM, Montreal, Quebec; and National Cancer Institute of Canada Clinical Trials Group, Queen\u2019s University, Kingston, Ontario, Canada; and Rh\u00f4ne-Poulenc Rorer, Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"R1-0562","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-111-4-273"},{"key":"R2-0562","doi-asserted-by":"publisher","DOI":"10.1097\/00001813-199506000-00001"},{"key":"R5-0562","unstructured":"Bissery  MC,   Vrignaud  P,   Riou  JF,  et al:  In vivo isolation and characterization of a docetaxel resistant B16 melanoma.   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