Disease relevance of Ixabepilone

• In a phase II trial, we evaluated the efficacy and safety of ixabepilone in women with metastatic and locally advanced breast cancer [1].
• Grades 3 and 4 toxicities experienced by more than 5% of patients included neutropenia (22%), fatigue (9%), and neuropathy (13%) on the ixabepilone arm, and neutropenia (29%), febrile neutropenia (9%), fatigue (9%), neuropathy (7%), and thrombosis (6%) on the ixabepilone + EMP arm [2].
• We evaluated ixabepilone (BMS-247550) in patients with metastatic hormone-refractory prostate cancer (HRPC) [3].
• RESULTS: At the MTD (10 mg/kg), ixabepilone induced objective responses (all tumors in a group achieved > or = 50% volume regression) in three of three rhabdomyosarcoma lines, three of five neuroblastomas, six of seven Wilms' tumor models, two of six osteosarcoma, and four of eight brain tumor models [4].
• The results of this study suggest that once every 21-day ixabepilone schedule should be pursued further in untreated gastric or gastroesophageal adenocarcinoma patients [5].
• Ixabepilone can cause tumor regression in some patients with metastatic renal cell carcinoma and could be considered in combination regimens with other therapies [6].

High impact information on Ixabepilone

• Microtubule stabilization occurred in tumor biopsies after treatment with ixabepilone [1].
• Compared with baseline levels, levels of both glu-terminated and acetylated alpha-tubulin were increased in tumor biopsies performed after ixabepilone therapy [1].
• EXPERIMENTAL DESIGN: Ixabepilone was administered i.v. every 4 days for three doses to scid mice bearing s.c. human rhabdomyosarcoma (three lines), neuroblastoma (four), Wilms' tumors (six), osteosarcoma (four), or brain tumors (seven) [4].
• Phase II trial of ixabepilone, an epothilone B analog, given daily for three days every three weeks, in metastatic breast cancer [7].
• A multi-center phase II study of BMS-247550 (Ixabepilone) by two schedules in patients with metastatic gastric adenocarcinoma previously treated with a taxane [5].

Chemical compound and disease context of Ixabepilone

• PURPOSE: To evaluate the antitumor activity and safety of the epothilone B analog, ixabepilone, with or without estramustine phosphate (EMP), in chemotherapy-naive patients with progressive castrate metastatic prostate cancer [2].
• Response rates in taxane-refractory metastatic breast cancer are relatively modest, but ixabepilone and patupilone have shown promising efficacy in hormone-refractory metastatic prostate cancer and in taxane-refractory ovarian cancer [8].

Biological context of Ixabepilone

• The maximum-tolerated dose was 8 mg/m(2) per day of ixabepilone administered as a 1-hour intravenous infusion daily for 3 consecutive days every 21 days [9].
• The pharmacokinetics of ixabepilone and two of its chemical degradation products were evaluated [10].

Anatomical context of Ixabepilone

• A Phase II trial of epothilone B analogue BMS-247550 (NSC #710428) ixabepilone, in patients with advanced pancreas cancer: a Southwest Oncology Group study [11].

Associations of Ixabepilone with other chemical compounds

• PURPOSE: Ixabepilone (BMS-247550) is an epothilone B analog that stabilizes microtubules and has antitumor activity in taxane-refractory patients in phase I studies [1].
• There are now increasing options also for second-line therapies in the palliative treatment of HRPC, and ongoing studies on new drugs such as satraplatin and ixabepilone will define the role of these agents in this setting [12].
• The epothilones ixabepilone, patupilone, BMS-310705, KOS-862 and ZK-EPO are in early clinical trials for cancer treatment [8].
• However, for doublets with docetaxel or second-line chemotherapy, multiple studies have shown interesting and promising results with calcitriol, thalidomide, bevacizumab, satraplatin, vaccines, ixabepilone, and atrasentan [13].
• The synergistic antitumor effect was greater with ixabepilone compared with paclitaxel [14].

Gene context of Ixabepilone

• Second-line PSA declines > or = 50% were achieved by 61% of patients (95% CI, 42-78%) who achieved a first-line PSA decline > or = 50% with ixabepilone, compared with 33% of patients (95% CI, 13-59%) who did not (P = 0.08) [15].
• Ixabepilone is a good CYP3A4 substrate in vitro; however, in humans, it is likely to be cleared by multiple mechanisms [16].

Analytical, diagnostic and therapeutic context of Ixabepilone

• PATIENTS AND METHODS: Patients were randomly assigned to receive ixabepilone (35 mg/m(2)) by intravenous infusion every 3 weeks with or without EMP 280 mg orally three times daily on days 1 to 5 [2].
• CONCLUSIONS: Second-line taxane chemotherapy after ixabepilone resulted in a substantial frequency of PSA declines [15].

References