{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:48:36Z","timestamp":1789742916133,"version":"4.0.1"},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[1994,8]]},"abstract":"\n PURPOSE<\/jats:title>\n A phase I study of paclitaxel infused over 96-hours was performed to determine toxicity, maximum-tolerated dose (MTD), and pharmacokinetics in patients with incurable lymphomas and solid tumors. A phase II study was performed at the MTD of paclitaxel in patients with doxorubicin\/mitoxantrone-refractory metastatic breast cancer.<\/jats:p>\n <\/jats:sec>\n \n PATIENTS AND METHODS<\/jats:title>\n In the phase I study, paclitaxel dose levels ranged from 120 to 160 mg\/m2, administered on a 21-day cycle. Patients with metastatic breast cancer who had either no response or a partial response (PR) to doxorubicin or mitoxantrone and had measurable disease were eligible for the phase I and II studies. Expression of the multidrug resistance (mdr-1) gene was determined in tumor biopsies by mRNA quantitative polymerase chain reaction.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n Twelve patients received a total of 73 cycles of paclitaxel on the phase I study. Dose-limiting mucositis and\/or grade IV granulocytopenia was reached at 160 mg\/m2, and 140 mg\/m2 was selected as the phase II dose. Thirty-six consecutive patients with metastatic breast cancer were treated, of whom three were not assessable. The median age was 49 years, with disease in the liver and\/or lung in 76%. Patients received a median of two prior regimens for metastatic disease, and 73% had no response to prior doxorubicin or mitoxantrone. Of 33 patients treated with paclitaxel, 16 patients (48%) achieved a PR and five (15%) achieved a minor response (MR). With a median potential follow-up duration of 60 weeks, the median progression-free and overall survival durations were 27 and 43 weeks, respectively. No correlation was found between extent of prior treatment or prior response to doxorubicin\/mitoxantrone, and response to paclitaxel. Paclitaxel pharmacokinetics showed a correlation between both granulocyte and mucosal toxicity, and serum steady-state concentrations (Css) more than 0.07 mumol\/L. Patients with liver metastases had significantly decreased paclitaxel clearance and higher paclitaxel Css. Levels of mdr-1 were uniformly low in all tumor biopsies studied.<\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n The recommended phase II dose of paclitaxel is 140 mg\/m2 in patients without liver metastases and 105 mg\/m2 in patients with liver metastases. Ninety-six-hour infusions of paclitaxel were effective and well tolerated in patients with doxorubicin\/mitoxantrone-refractory breast cancer. Prolonged infusion schedules may be more effective than shorter schedules and deserve further study.<\/jats:p>\n <\/jats:sec>","DOI":"10.1200\/jco.1994.12.8.1621","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T08:06:03Z","timestamp":1487837163000},"page":"1621-1629","source":"Crossref","is-referenced-by-count":146,"title":["Paclitaxel in doxorubicin-refractory or mitoxantrone-refractory breast cancer: a phase I\/II trial of 96-hour infusion."],"prefix":"10.1200","volume":"12","author":[{"given":"W H","family":"Wilson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S L","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Bryant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R E","family":"Wittes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Bates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Fojo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S M","family":"Steinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B R","family":"Goldspiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Herdt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"O'Shaughnessy","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.1994.12.8.1621","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T15:54:23Z","timestamp":1653494063000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.1994.12.8.1621"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,8]]},"references-count":0,"journal-issue":{"issue":"8","published-print":{"date-parts":[[1994,8]]}},"alternative-id":["10.1200\/JCO.1994.12.8.1621"],"URL":"https:\/\/doi.org\/10.1200\/jco.1994.12.8.1621","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,8]]}}}