{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T10:39:22Z","timestamp":1783507162044,"version":"3.55.0"},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[1994,9]]},"abstract":"PURPOSE<\/jats:title> The feasibility of administering vinorelbine (Navelbine, Burroughs Wellcome Co, Research Triangle Park, NC), a semisynthetic vinca alkaloid with broad activity, as a liquid-filled gelatin capsule was evaluated in a bioavailability (F) and pharmacokinetic study. <\/jats:p><\/jats:sec>PATIENTS AND METHODS<\/jats:title> Each of 17 cancer patients had pharmacokinetic studies performed after receiving vinorelbine 30 mg\/m2 intravenously (IV), which is the maximum-tolerated dose (MTD) for weekly IV administration, and twice after receiving the oral formulation at a nominal dose of 100 mg\/m2. Subsequently, these patients and 10 other subjects received the oral formulation at a dose of 100 mg\/m2\/wk to evaluate the feasibility of chronic oral administration. <\/jats:p><\/jats:sec>RESULTS<\/jats:title> Plasma drug disposition was well described by a triphasic model. Mean central volume of distribution and steady-state volume of distribution (Vss) were large (0.66 +\/- 0.46 L\/kg and 20.02 +\/- 8.55 L\/kg, respectively); the mean harmonic terminal half-life (t1\/2) was long (18 hours); and the high mean clearance (CI) rate (0.80 +\/- 0.68 L\/h\/kg) approached hepatic blood flow. F was low (0.27 +\/- 12), and absorption was rapid (mean time of maximum plasma concentration [Tmax], 0.91 +\/- 0.22 hours). Absorption parameters after the first and second oral doses were similar, with mean F values of 0.27 +\/- 0.14 and 0.25 +\/- 0.11, respectively. Coefficients of variability (CVs) for F, maximum plasma concentration (Cmax), and Tmax were 32%, 42%, and 78%, respectively, indicating moderate intraindividual variability. The pharmacologic profile of this oral formulation indicates that there is a large first-pass effect. Neutropenia was the principal toxicity of oral vinorelbine. Grade 3 or 4 neutropenia occurred in 63% of patients, but only 11% developed neutropenia and infection. Nausea, vomiting, and diarrhea were also common with oral administration, but these effects were rarely severe and could be ameliorated by using a divided-dose schedule and\/or prophylactic antiemetic and antidiarrheal agents. The mean nominal oral dose was 82 mg\/m2, and the mean percentage of intended dose that was received was 92%. Although dose escalations were permitted for negligible toxicity, doses were not escalated to greater than 100 mg\/m2\/wk in any patient. Vinorelbine given as a liquid-filled gelatin capsule at 100 mg\/m2 provided equivalent pharmacologic exposure as 30 mg\/m2 IV. <\/jats:p><\/jats:sec>CONCLUSION<\/jats:title> The oral administration of vinorelbine, specifically as a liquid-filled, soft gelatin capsule, is a feasible route of administration. Weekly oral dosing at 100 mg\/m2 induces a consistent degree of myelosuppression, but the high frequency of grade 3 or 4 neutropenia, albeit brief and uncomplicated, warrants the recommendation of a slightly lower starting dose, ie, 80 mg\/m2\/d, for subsequent phase II evaluations, especially in heavily pretreated patients. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.1994.12.9.1754","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T12:46:52Z","timestamp":1487854012000},"page":"1754-1763","source":"Crossref","is-referenced-by-count":46,"title":["Pharmacokinetic, bioavailability, and feasibility study of oral vinorelbine in patients with solid tumors."],"prefix":"10.1200","volume":"12","author":[{"given":"E K","family":"Rowinsky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D A","family":"Noe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D L","family":"Trump","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E P","family":"Winer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V S","family":"Lucas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W A","family":"Wargin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J A","family":"Hohneker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Lubejko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S E","family":"Sartorius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D S","family":"Ettinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.1994.12.9.1754","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T19:53:19Z","timestamp":1653508399000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.1994.12.9.1754"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,9]]},"references-count":0,"journal-issue":{"issue":"9","published-print":{"date-parts":[[1994,9]]}},"alternative-id":["10.1200\/JCO.1994.12.9.1754"],"URL":"https:\/\/doi.org\/10.1200\/jco.1994.12.9.1754","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,9]]}}}