Efficacy of low-dose capecitabine in metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1065-1065
Author(s):  
Caitlin Bertelsen ◽  
Lingyun Ji ◽  
Christy Ann Russell ◽  
Darcy V. Spicer ◽  
Agustin Garcia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Flat Dose ◽  
Measurable Disease ◽  
Phase Iii Trials

1065 Background: The FDA-approved dose of capecitabine (cape) of 1250mg/m2 twice daily (BID) is associated with treatment-limiting toxicities. Published reports suggest that lower starting doses of cape can be as effective as the approved dose in treating metastatic breast cancer (MBC). We compared the efficacy of lower than previously published doses of cape with results of registrational Phase III trials using the approved dose. Methods: We performed a retrospective analysis of patients treated at the University of Southern California hospitals who received cape as the first, second, or third line of chemotherapy for MBC to determine the progression-free survival (PFS) associated with low starting doses. The primary endpoint was PFS among patients with measurable disease, and secondary aims were to analyze the relationships between PFS and various clinical characteristics for all patients. Results: Patients (n=84) received a median cape dose of 565 mg/m2 BID, often administered as a flat dose (not adjusted for body surface area) of 1000 mg BID. Median PFS among patients with measurable disease (n=62) was 4.1 months (95% confidence interval or CI = 2.9-5.7), which was similar to the median PFS values of 4.4 months (95% CI = 4.14-5.42, n=480) (Sparano et al. JCO 2010;28:3256) and 4.2 months (95% CI = 3.81-4.50, n=377) (Thomas et al. JCO 2008;25:5210) for single-agent cape reported in the major trials with similar eligibility criteria. Among all patients, PFS was shorter in measurable disease, triple negative and HER2+ subtypes, and was similar in all lines of therapy. Only two patients (2.4%) discontinued cape due to toxicity. Conclusions: These data support the efficacy of very low doses of cape for MBC. Prospective randomized controlled trials testing lower starting doses of cape are needed to optimize the benefit/risk ratio. [Table: see text]

Phase III Trial of Sunitinib in Combination With Capecitabine Versus Capecitabine Monotherapy for the Treatment of Patients With Pretreated Metastatic Breast Cancer

2013 ◽  
Vol 31 (23) ◽  
pp. 2870-2878 ◽  
Author(s):  
John P. Crown ◽  
Véronique Diéras ◽  
Elzbieta Staroslawska ◽  
Denise A. Yardley ◽  
Thomas Bachelot ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Phase Iii Trial ◽  
Free Survival

Purpose Metastatic breast cancer (MBC) remains an incurable illness in the majority of cases, despite major therapeutic advances. This may be related to the ability of breast tumors to induce neoangiogenesis, even in the face of cytotoxic chemotherapy. Sunitinib, an inhibitor of key molecules involved in neoangiogenesis, has an established role in the treatment of metastatic renal cell and other cancers and demonstrated activity in a phase II trial in MBC. We performed a randomized phase III trial comparing sunitinib plus capecitabine (2,000 mg/m2) with single-agent capecitabine (2,500 mg/m2) in patients with heavily pretreated MBC. Patients and Methods Eligibility criteria included MBC, prior therapy with anthracyclines and taxanes, one or two prior chemotherapy regimens for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. The primary end point was progression-free survival, for which the study had 90% power to detect a 50% improvement (from 4 to 6 months). Results A total of 442 patients were randomly assigned. Progression-free survival was not significantly different between the treatment arms, with medians of 5.5 months (95% CI, 4.5 to 6.0) for the sunitinib plus capecitabine arm and 5.9 months (95% CI, 5.4 to 7.6) for the capecitabine monotherapy arm (hazard ratio, 1.22; 95% CI, 0.95 to 1.58; one-sided P = .941). There were no significant differences in response rate or overall survival. Toxicity, except for hand-foot syndrome, was more severe in the combination arm. Conclusion The addition of sunitinib to capecitabine does not improve the clinical outcome of patients with MBC pretreated with anthracyclines and taxanes.

scholarly journals Ixabepilone: Overview of Effectiveness, Safety, and Tolerability in Metastatic Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Nuhad K. Ibrahim
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Management Strategies ◽  
Unmet Need ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Phase Iii Trials ◽  
Microtubule Stabilizer

Treatment algorithms for metastatic breast cancer describe sequential treatment with chemotherapy and, if appropriate, targeted therapy for as long as the patient receives benefit. The epothilone ixabepilone is a microtubule stabilizer approved as a monotherapy and in combination with capecitabine for the treatment of metastatic breast cancer in patients with demonstrated resistance to anthracyclines and taxanes. While chemotherapy and endocrine therapy form the backbone of treatment for metastatic breast cancer, the epothilone drug class has distinguished itself for efficacy and safety among patients with disease progression during treatment with chemotherapy. In phase III trials, ixabepilone has extended progression-free survival and increased overall response rates, with a manageable toxicity profile. Recent analyses of subpopulations within large pooled datasets have characterized the clinical benefit for progression-free survival and overall survival for ixabepilone in special populations, such as patients with triple-negative breast cancer or those who relapsed within 12 months of prior treatment. Additional investigation settings for ixabepilone therapy discussed here include adjuvant therapy, weekly dosing schedules, and ixabepilone in new combinations of treatment. As with other microtubule stabilizers, ixabepilone treatment can lead to peripheral neuropathy, but evidence-based management strategies may reverse these symptoms. Dose reductions did not appear to have an impact on the efficacy of ixabepilone plus capecitabine. Incorporation of ixabepilone into individualized treatment plans can extend progression-free survival in a patient population that continues to represent an unmet need.

Ixabepilone Plus Capecitabine for Metastatic Breast Cancer Progressing After Anthracycline and Taxane Treatment

2007 ◽  
Vol 25 (33) ◽  
pp. 5210-5217 ◽  
Author(s):  
Eva S. Thomas ◽  
Henry L. Gomez ◽  
Rubi K. Li ◽  
Hyun-Cheol Chung ◽  
Luis E. Fein ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Options ◽  
Single Agent ◽  
Objective Response ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival

PurposeEffective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with capecitabine in this setting. This study was designed to compare ixabepilone plus capecitabine versus capecitabine alone in anthracycline-pretreated or -resistant and taxane-resistant locally advanced or metastatic breast cancer.Patients and MethodsSeven hundred fifty-two patients were randomly assigned to ixabepilone 40 mg/m2intravenously on day 1 of a 21-day cycle plus capecitabine 2,000 mg/m2orally on days 1 through 14 of a 21-day cycle, or capecitabine alone 2,500 mg/m2on the same schedule, in this international phase III study. The primary end point was progression-free survival evaluated by blinded independent review.ResultsIxabepilone plus capecitabine prolonged progression-free survival relative to capecitabine (median, 5.8 v 4.2 months), with a 25% reduction in the estimated risk of disease progression (hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P = .0003). Objective response rate was also increased (35% v 14%; P < .0001). Grade 3/4 treatment-related sensory neuropathy (21% v 0%), fatigue (9% v 3%), and neutropenia (68% v 11%) were more frequent with combination therapy, as was the rate of death as a result of toxicity (3% v 1%, with patients with liver dysfunction [≥ grade 2 liver function tests] at greater risk). Capecitabine-related toxicities were similar for both treatment groups.ConclusionIxabepilone plus capecitabine demonstrates superior efficacy to capecitabine alone in patients with metastatic breast cancer pretreated or resistant to anthracyclines and resistant to taxanes.

Phase III Study of Intravenous Vinorelbine in Combination With Epirubicin Versus Epirubicin Alone in Patients With Advanced Breast Cancer: A Scandinavian Breast Group Trial (SBG9403)

2004 ◽  
Vol 22 (12) ◽  
pp. 2313-2320 ◽  
Author(s):  
Bent Ejlertsen ◽  
Henning T. Mouridsen ◽  
Sven T. Langkjer ◽  
Jorn Andersen ◽  
Johanna Sjöström ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Complete Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Severe Toxicity ◽  
Free Survival

Purpose To determine whether the addition of intravenous (IV) vinorelbine to epirubicin increased the progression-free survival in first-line treatment of metastatic breast cancer. Patients and Methods A total of 387 patients were randomly assigned to receive IV epirubicin 90 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8, or epirubicin 90 mg/m2 IV on day 1. Both regimens were given every 3 weeks for a maximum of 1 year but discontinued prematurely in the event of progressive disease or severe toxicity. In addition, epirubicin was discontinued at a cumulative dose of 1,000 mg/m2 (950 mg/m2 from June 1999). Prior anthracycline-based adjuvant chemotherapy and prior chemotherapy for metastatic breast cancer was not allowed. Reported results were all based on intent-to-treat analyses. Results Overall response rates to vinorelbine and epirubicin, and epirubicin alone, were 50% and 42%, respectively (P = .15). The complete response rate was significantly superior in the combination arm (17% v 10%; P = .048) as was median duration of progression-free survival (10.1 months v 8.2 months; P = .019). Median survival was similar in the two arms (19.1 months v 18.0 months; P = .50). Leukopenia related complications, stomatitis, and peripheral neuropathy were more common in the combination arm. The incidences of cardiotoxicity and constipation were similar in both arms. Conclusion Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival, but not in terms of survival.

Lapatinib and HER2 status: Results of a meta-analysis of randomized phase III trials in metastatic breast cancer

2010 ◽  
Vol 36 (5) ◽  
pp. 410-415 ◽  
Author(s):  
Eitan Amir ◽  
Alberto Ocaña ◽  
Bostjan Seruga ◽  
Orit Freedman ◽  
Mark Clemons
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Her2 Status ◽  
Phase Iii Trials
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