{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T07:01:55Z","timestamp":1768719715680,"version":"3.49.0"},"reference-count":24,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[1999,6]]},"abstract":"<jats:p> PURPOSE: To evaluate the feasibility of administering the oral fluoropyrimidine capecitabine in combination with paclitaxel, to characterize the principal toxicities of the combination, to recommend doses for subsequent disease-directed studies, and to determine whether significant pharmacokinetic interactions occur between these agents when combined. <\/jats:p><jats:p> PATIENTS AND METHODS: Sixty-six courses of capecitabine and paclitaxel were administered to 17 patients in a two-stage dose-escalation study. Paclitaxel was administered as a 3-hour intravenous (IV) infusion every 3 weeks, and capecitabine was administered continuously as two divided daily doses. During stage I, capecitabine was escalated to a target dose of 1,657 mg\/m<jats:sup>2<\/jats:sup>\/d, whereas the paclitaxel dose was fixed at 135 mg\/m<jats:sup>2<\/jats:sup>. In stage II, paclitaxel was increased to a target dose of 175 mg\/m<jats:sup>2<\/jats:sup>, and the capecitabine dose was the maximum established in stage I. Pharmacokinetics were characterized for each drug when given alone and concurrently. <\/jats:p><jats:p> RESULTS: Myelosuppression, predominately neutropenia, was the principal dose-limiting toxicity (DLT). Othertoxicities included hand-foot syndrome, diarrhea, hyperbilirubinemia, skin rash, myalgia, and arthralgia. Two patients treated with capecitabine 1,657 mg\/m<jats:sup>2<\/jats:sup>\/d and paclitaxel 175 mg\/m<jats:sup>2<\/jats:sup> developed DLTs, whereas none of six patients treated with capecitabine 1,331 mg\/m<jats:sup>2<\/jats:sup>\/d and paclitaxel 175 mg\/m<jats:sup>2<\/jats:sup> developed DLTs during course 1. Pharmacokinetic studies indicated that capecitabine and paclitaxel did not affect the pharmacokinetic behavior of each other. No major antitumor responses were noted. <\/jats:p><jats:p> CONCLUSION: Recommended combination doses of continuous capecitabine and paclitaxel are capecitabine 1,331 mg\/m<jats:sup>2<\/jats:sup>\/d and paclitaxel 175 mg\/m<jats:sup>2<\/jats:sup>\/d IV every 3 weeks. Favorable preclinical mechanistic interactions between capecitabine and paclitaxel, as well as an acceptable toxicity profile without clinically relevant pharmacokinetic interactions, support the performance of disease-directed evaluations of this combination. <\/jats:p>","DOI":"10.1200\/jco.1999.17.6.1915","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T06:13:07Z","timestamp":1487916787000},"page":"1915-1915","source":"Crossref","is-referenced-by-count":61,"title":["Phase I and Pharmacokinetic Study of the Oral Fluoropyrimidine Capecitabine in Combination With Paclitaxel in Patients With Advanced Solid Malignancies"],"prefix":"10.1200","volume":"17","author":[{"given":"Miguel A.","family":"Villalona-Calero","sequence":"first","affiliation":[{"name":"From the Institute for Drug Development, Cancer Therapy and Research Center, and The University of Texas Health Science Center at San Antonio, San Antonio; Brooke Army Medical Center, Fort Sam Houston, TX; and Hoffmann-LaRoche, Inc, Nutley, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey R.","family":"Weiss","sequence":"additional","affiliation":[{"name":"From the Institute for Drug Development, Cancer Therapy and Research Center, and The University of Texas Health Science Center at San Antonio, San Antonio; Brooke Army Medical Center, Fort Sam Houston, TX; and Hoffmann-LaRoche, Inc, Nutley, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard A.","family":"Burris","sequence":"additional","affiliation":[{"name":"From the Institute for Drug Development, Cancer Therapy and Research Center, and The University of Texas Health Science Center at San Antonio, San Antonio; Brooke Army Medical Center, Fort Sam Houston, TX; and Hoffmann-LaRoche, Inc, Nutley, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maura","family":"Kraynak","sequence":"additional","affiliation":[{"name":"From the Institute for Drug Development, Cancer Therapy and Research Center, and The University of Texas Health Science Center at San Antonio, San Antonio; Brooke Army Medical Center, Fort Sam Houston, TX; and Hoffmann-LaRoche, Inc, Nutley, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gladys","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"From the Institute for Drug Development, Cancer Therapy and Research Center, and The University of Texas Health Science Center at San Antonio, San Antonio; Brooke Army Medical Center, Fort Sam Houston, TX; and Hoffmann-LaRoche, Inc, Nutley, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald L.","family":"Drengler","sequence":"additional","affiliation":[{"name":"From the Institute for Drug Development, Cancer Therapy and Research Center, and The University of Texas Health Science Center at San Antonio, San Antonio; Brooke Army Medical Center, Fort Sam Houston, TX; and Hoffmann-LaRoche, Inc, Nutley, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Gail","family":"Eckhardt","sequence":"additional","affiliation":[{"name":"From the Institute for Drug Development, Cancer Therapy and Research Center, and The University of Texas Health Science Center at San Antonio, San Antonio; Brooke Army Medical Center, Fort Sam Houston, TX; and Hoffmann-LaRoche, Inc, Nutley, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Reigner","sequence":"additional","affiliation":[{"name":"From the Institute for Drug Development, Cancer Therapy and Research Center, and The University of Texas Health Science Center at San Antonio, San Antonio; Brooke Army Medical Center, Fort Sam Houston, TX; and Hoffmann-LaRoche, Inc, Nutley, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judy","family":"Moczygemba","sequence":"additional","affiliation":[{"name":"From the Institute for Drug Development, Cancer Therapy and Research Center, and The University of Texas Health Science Center at San Antonio, San Antonio; Brooke Army Medical Center, Fort Sam Houston, TX; and Hoffmann-LaRoche, Inc, Nutley, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans Ulrich","family":"Burger","sequence":"additional","affiliation":[{"name":"From the Institute for Drug Development, Cancer Therapy and Research Center, and The University of Texas Health Science Center at San Antonio, San Antonio; Brooke Army Medical Center, Fort Sam Houston, TX; and Hoffmann-LaRoche, Inc, Nutley, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Griffin","sequence":"additional","affiliation":[{"name":"From the Institute for Drug Development, Cancer Therapy and Research Center, and The University of Texas Health Science Center at San Antonio, San Antonio; Brooke Army Medical Center, Fort Sam Houston, TX; and Hoffmann-LaRoche, Inc, Nutley, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel D.","family":"Von Hoff","sequence":"additional","affiliation":[{"name":"From the Institute for Drug Development, Cancer Therapy and Research Center, and The University of Texas Health Science Center at San Antonio, San Antonio; Brooke Army Medical Center, Fort Sam Houston, TX; and Hoffmann-LaRoche, Inc, Nutley, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric K.","family":"Rowinsky","sequence":"additional","affiliation":[{"name":"From the Institute for Drug Development, Cancer Therapy and Research Center, and The University of Texas Health Science Center at San Antonio, San Antonio; Brooke Army Medical Center, Fort Sam Houston, TX; and Hoffmann-LaRoche, Inc, Nutley, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"R1-1915","unstructured":"Ishitsuka  H,  Miwa  M,  Ishikawa  T, et al: Capecitabine: An orally available fluoropyrimidine with tumor selective activity.  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