دورية أكاديمية
Phase I trial of weekly paclitaxel and BMS-214662 in patients with advanced solid tumors.
| العنوان: | Phase I trial of weekly paclitaxel and BMS-214662 in patients with advanced solid tumors. |
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| المؤلفون: | Bailey HH; University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin 53792, USA. hhbailey@wisc.edu, Alberti DB, Thomas JP, Mulkerin DL, Binger KA, Gottardis MM, Martell RE, Wilding G |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2007 Jun 15; Vol. 13 (12), pp. 3623-9. Date of Electronic Publication: 2007 May 17. |
| نوع المنشور: | Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1078-0432 (Print) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Antineoplastic Combined Chemotherapy Protocols/*therapeutic use , Benzodiazepines/*administration & dosage , Imidazoles/*administration & dosage , Neoplasms/*drug therapy , Paclitaxel/*administration & dosage, Adult ; Aged ; Benzodiazepines/adverse effects ; Benzodiazepines/pharmacokinetics ; Female ; Humans ; Imidazoles/adverse effects ; Imidazoles/pharmacokinetics ; Male ; Maximum Tolerated Dose ; Middle Aged ; Paclitaxel/adverse effects ; Paclitaxel/pharmacokinetics |
| مستخلص: | Purpose: To assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacodynamics, and antitumor activity of continuous weekly-administered paclitaxel and BMS-214662, a novel farnesyl transferase inhibitor. Experimental Design: Patients were treated every week as tolerated with i.v. paclitaxel (fixed dose, 80 mg/m(2)/wk) administered over 1 h followed by i.v. BMS-214662 (escalating doses, 80-245 mg/m(2)/wk) over 1 h starting 30 min after completion of paclitaxel. Results: Twenty-six patients received 94 courses (one course, 21 days) of study treatment. Two patients received five courses of BMS-214662 as a weekly 24-h infusion (209 mg/m(2)/wk). The most common toxicities were grade 1 to 2 nausea/vomiting and/or diarrhea. DLTs observed at or near the MTD (200 mg/m(2)/wk) were grade 4 febrile neutropenia with sepsis occurring on day 2 of course 1 (245 mg/m(2)/wk), reversible grade 3 to 4 serum transaminase increases on day 2, and grade 3 diarrhea (200 and 245 mg/m(2)/wk). Objective partial responses were observed in patients with pretreated head and neck, ovarian, and hormone-refractory prostate carcinomas, and leiomyosarcoma. The observed pharmacokinetics of paclitaxel and BMS-214662 imply no interaction between the two. Significant inhibition (>80%) of farnesyl transferase activity in peripheral mononuclear cells was observed at the end of BMS-214662 infusion. Conclusions: Pretreated patients with advanced malignancies can tolerate weekly paclitaxel and BMS-214662 at doses that achieve objective clinical benefit. Due to multiple DLTs occurring at the expanded MTD, the recommended phase 2 dose and schedule is paclitaxel (80 mg/m(2) over 1 h) and BMS-214662 (160 mg/m(2) over 1 h) administered weekly. |
| معلومات مُعتمدة: | M01RR03186 United States RR NCRR NIH HHS |
| المشرفين على المادة: | 0 (Imidazoles) 12794-10-4 (Benzodiazepines) L2U9GFD244 (7-cyano-2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine) P88XT4IS4D (Paclitaxel) |
| تواريخ الأحداث: | Date Created: 20070519 Date Completed: 20071004 Latest Revision: 20181228 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1158/1078-0432.CCR-07-0158 |
| PMID: | 17510207 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1078-0432 |
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| DOI: | 10.1158/1078-0432.CCR-07-0158 |