Phase II Clinical Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Metastatic and Locally Advanced Breast Cancer

Low, Jennifer A.; Wedam, Suparna; Lee, James J.; Berman, Arlene; Brufsky, Adam; Yang, Sherry X.; Poruchynsky, Marianne S.; Steinberg, Seth M.; Mannan, N.; Fojo, Tito; Swain, Sandra M.

doi:10.1200/jco.2005.10.024

Cited by 202 publications

(108 citation statements)

References 21 publications

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…81 Currently, these preclinical observations are translating into clinical effects: Adjuvant ixabepilone has demonstrated antitumor activity in taxane-refractory patients in Phase I and II studies. 69,82 Tumor response to EPO-906 also has been demonstrated in Phase I trials in patients with several cancers, including BC, and Phase II studies are in progress.…”

Section: Identifying New Agents For Neoadjuvant Therapy In Breast Cancermentioning

confidence: 99%

“…68 Of these, ixabepilone (BMS247550) is the furthest along in terms of clinical development and has shown promising efficacy and a manageable safety profile in a range of tumor types, including multiresistant BC. [69][70][71][72][73][74][75] EPO-906 also has shown promising activity in a Phase II trial of gastric cancer, 76 and patients currently are being recruited for a Phase III trial in ovarian cancer (see www.clinicaltrials.gov; NCT00262990). In addition, epothilone D (KOS-862) is undergoing Phase II clinical evaluation in BC and lung cancer.…”

Section: Identifying New Agents For Neoadjuvant Therapy In Breast Cancermentioning

confidence: 99%

See 1 more Smart Citation

Preoperative chemotherapy treatment of breast cancer—A review

Buzdar

2007

Cancer

View full text Add to dashboard Cite

Despite proven benefits of neoadjuvant chemotherapy in patients with locally advanced, invasive breast cancer, no regimen is recommended as the treatment of choice. Neoadjuvant chemotherapy regimens encompass single-agent and combination therapy and sequential treatment. For this report, the author reviewed the literature to determine which regimen, if any, was most beneficial.The results indicated that studies have yielded a wide range of response rates, but no single regimen has emerged as a clear leader. The literature is compounded further by lack of standardized criteria to determine pathologic complete response (which is predictive of survival benefits) and between-study variation in the stringency by which this endpoint is defined. Given the lack of a preferred treatment regimen in the neoadjuvant setting, identifying patients who are likely to respond to specific agents could inform treatment decisions, improve treatment outcomes, and aid in avoiding unnecessary exposure to potential toxicities. The development of novel agents for use alone or in combination with existing agents may improve response rates further in the neoadjuvant setting, especially because a significant proportion of breast tumors can be resistant to many current antineoplastic agents. Particularly noteworthy are the epothilones and their analogs because of their low susceptibility to common tumor-resistance mechanisms. Initial data have indicated that ixabepilone, which is an epothilone analog, has activity in the neoadjuvant setting, and predictive factors for response have been identified. The future of neoadjuvant therapy lies in tailoring treatment to individual patients by identifying response predictors and developing novel agents. This ultimately may lead to improved outcomes for women with breast cancer.

show abstract

Section: Identifying New Agents For Neoadjuvant Therapy In Breast Cancermentioning

confidence: 99%

Section: Identifying New Agents For Neoadjuvant Therapy In Breast Cancermentioning

confidence: 99%

Preoperative chemotherapy treatment of breast cancer—A review

Buzdar

2007

Cancer

View full text Add to dashboard Cite

show abstract

“…Docetaxel and vinorelbine were ineffective in these cell lines (61). (63,64). Ixabepilone has shown clinical efficacy and acceptable tolerability, as monotherapy and in combination with capecitabine, in patients with MBC, including those with disease resistant to anthracyclines, taxanes, and/or capecitabine (14 -16, 62 -65).…”

Section: Ixabepilone In Biii-tubulin^overexpressing Cellsmentioning

confidence: 99%

Ixabepilone: targeting βIII-tubulin expression in taxane-resistant malignancies

Dumontet

Jordan

Lee

2009

Molecular Cancer Therapeutics

104

View full text Add to dashboard Cite

Microtubule-targeting agents, such as taxanes and epothilones, block mitosis and cell proliferation by targeting the dynamics of the cytoskeleton. The taxanes are widely used for treatment of various malignancies, but primary and acquired resistance to chemotherapy remains a significant clinical concern. Class I, II, III, IV, and V B-tubulin isotypes are expressed in human tumors. Overexpression of the BIII-tubulin isotype is one mechanism that can render tumor cells resistant to taxanes. The relative expression of BIII-tubulin correlates with clinical outcomes in several tumor types, including breast cancer, non -small cell lung cancer, and ovarian cancer. A novel analogue of epothilone B, ixabepilone, has recently been approved in combination with capecitabine for the treatment of patients with anthracycline-and taxaneresistant locally advanced or metastatic breast cancer and as monotherapy in patients whose tumors are resistant or refractory to an anthracycline, a taxane, and capecitabine. The significant antitumor activity of ixabepilone in taxaneresistant tumors may be related to its preferential suppression of the dynamic instability of A/BIII-microtubules in cells expressing high levels of BIII-tubulin.

show abstract

“…Moderate activity has been observed with irinotecan and pemetrexed yielding ORRs of 14 -26% and 10 -26%, respectively, in patients with MBC after anthracycline and/ or taxane exposure (Calvert, 2003;Heinemann, 2003;Perez et al, 2004). In a phase II trial with ixabepilone, 37 women with metastatic and locally advanced breast cancer who had received paclitaxel and/or docetaxel as prior neoadjuvant, adjuvant or metastatic therapy, the ORR was 22% and median duration of response 3.8 months; the median PFS was established at 2.8 months (Low et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Vinflunine: a new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy

Campone

Cortés

Vorobiof³

et al. 2006

Br J Cancer

View full text Add to dashboard Cite

To evaluate the single agent activity, pharmacokinetics and tolerability of the novel tubulin targeted agent vinflunine (VFL) (320 mg m À2 q 21 days) as second-line chemotherapy in patients with metastatic breast carcinoma (MBC). All patients had disease progression after anthracycline/taxane (A/T) therapy. They could have received a nonanthracycline adjuvant treatment and subsequently received a first-line A/T combination for advanced/metastatic disease; or relapsed 46 months after completion of adjuvant A/T therapy and were subsequently treated with the alternative agent; or relapsed within 6 months from an adjuvant A/T combination. Objective response was documented in 18 of 60 patients enrolled (RR: 30% (95% confidence interval (CI): 18.9 -43.2%)). Among the responders, seven patients had relapsed during a period of o3 months from taxane-based regimen yielding a RR of 33.3%. The median duration of response was 4.8 months (95% CI: 4.2 -7.2), median progression-free survival was 3.7 months (95% CI: 2.8 -4.2) and median overall survival was 14.3 months (95% CI: 9.2 -19.6). The most frequent adverse event was neutropenia (grade 3 in 28.3% and grade 4 in 36.7% of patients). No febrile neutropenia was observed. Fatigue (grade 3 in 16.7% of patients) and constipation (grade 3 in 11.7% of patients) were also common; these were non-cumulative and manageable permitting achievement of a good relative dose intensity of 93.5%. Vinflunine is an active agent with acceptable tolerance in the management of MBC patients previously treated with (A/T)-based regimens. These encouraging phase II results warrant further investigation of this novel agent in combination with other active agents in this setting or in earlier stages of disease.

show abstract

Phase II Clinical Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Metastatic and Locally Advanced Breast Cancer

Abstract: An objective response was seen in 22% of the patients in a population who had been previously treated with a taxane. Sensory neuropathy was mild with grade 3 neurotoxicity rarely seen. Microtubule stabilization occurred in tumor biopsies after treatment with ixabepilone.

Cited by 202 publications

References 21 publications

Preoperative chemotherapy treatment of breast cancer—A review

Preoperative chemotherapy treatment of breast cancer—A review

Ixabepilone: targeting βIII-tubulin expression in taxane-resistant malignancies

Vinflunine: a new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy

Contact Info

Product

Resources

About