scholarly journals Ixabepilone as Monotherapy or in Combination with Capecitabine for the Treatment of Advanced Breast Cancer

2011 ◽  
Vol 5 ◽  
pp. BCBCR.S5331 ◽  
Author(s):  
Katherine H. Rak Tkaczuk
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Response Rate ◽  
Locally Advanced Breast Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Advanced Breast ◽  
Prior Exposure ◽  
Phase Iii ◽  
Overall Response

Breast Cancer is the most prevalent cancer in the world with 4.4 million survivors up to 5 years following the diagnosis. 1 In the US alone approximately forty thousand women die annually of metastatic breast cancer (MBC). Despite many effective systemic treatment options approximately 50% of women with MBC succumb to the disease within 24 months of the diagnosis. 2 Ixabepilone is a novel, first in class member of the epothilone class of antineoplastic agents. Ixabepilone is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and Capecitabine. Ixabepilone is also indicated in combination with Capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated. Ixabepilone was extensively studied as a single agent in patients with MBC and was found to be effective and well tolerated with a predictable and manageable safety profile. Not surprisingly prior exposure to anthracyclines and taxanes affects significantly the potential for response to therapy with single agent Ixabepilone in metastatic setting. MBC patients with taxane resistant MBC have objective response rate (RR) of 12%, patients with prior low exposure to taxanes and/or resistance RR = 22%, Ixabepilone treatment after adjuvant anthracycline therapy exposure renders RR = 42% and in Taxane naïve patients RR = 57%. In two large phase III studies of Ixabepilone + Capecitabine versus Capecitabine alone, progression free survival (PFS) and overall response rates (RR) were higher in the combination treatment arms, but no survival advantage was seen overall. Treatment with Ixabepilone + Capecitabine in a phase II study resulted in an overall response rate (ORR) of 23% in ER/PR/HER2 negative, triple-negative breast cancer patients (TNBC) while ORR of 31% was seen in a preplanned pooled analysis of TNBC in the phase III trials of Ixabepilone + Capecitabine. Significantly prolonged median PFS was seen for TNBC treated with the combination of Ixabepilone + Capecitabine compared to Capecitabine alone 4.2 vs. 1.7 months respectively. Ixabepilone as single agent appears to show excellent antitumor activity in patients with TNBC MBC. Addition of Ixabepilone to Capecitabine results in approximately doubling in median PFS for TNBC versus Capecitabine alone. Single agent Ixabepilone is generally well tolerated, and its toxicity profile does not overlap with that of Capecitabine and therefore depending on prior exposure to chemotherapy both single agent Ixabepilone or in combination with Capecitabine can be used safely and effectively for treatment of advanced breast cancer.

scholarly journals A Phase II Study of Sequential Treatment with Anthracycline and Taxane Followed by Eribulin in Patients with HER2-negative, Locally Advanced Breast Cancer (JBCRG-17)

2021 ◽  
Author(s):  
Ippei Fukada ◽  
Yoshinori Ito ◽  
Naoto Kondo ◽  
Shoichiro Ohtani ◽  
Masaya Hattori ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Clinical Response ◽  
Phase Ii ◽  
Response Rate ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Advanced Breast ◽  
Clinical Response Rate ◽  
Sequential Administration

Abstract PurposeThe sequence of taxanes (T) followed by anthracyclines (A) as neoadjuvant chemotherapy (NAC) has been the standard of care for almost 20 years for locally advanced breast cancer (LABC). Sequential administration of eribulin (E) following A/T could provide a greater response rate for women with LABC.MethodsIn this single-arm, multicenter, Phase II prospective study, the patients received 4 cycles of the FEC regimen and 4 cycles of taxane. After the A/T-regimen, 4 cycles of E were administered followed by surgical resection. The primary endpoint was the clinical response rate. Eligible patients were women aged 20 years or older, with histologically confirmed invasive breast cancer, clinical Stage IIIA (T2-3 and N2 only), Stage IIIB, and Stage IIIC, HER2-negative.ResultsA preplanned interim analysis aimed to validate the trial assumptions was conducted after treatment of 20 patients and demonstrated that clinical progressive disease (cPD) rates in the E phase were significantly higher (30%) than assumed. Therefore, the Independent Data Monitoring Committee recommended stopping the study. Finally, 53 patients were enrolled, and 26 patients received the A/T/E-regimen. The overall observed clinical response rate (RR) was 73% (19/26); RRs were 77% (20/26) in the AT phase and 23% (6/26) in the E phase. Thirty percent (8/26) of patients had PD in the E phase, 6 of whom had achieved cCR/PR in the AT phase. Reported grade >3 AEs related to E were neutropenia (42%), white blood cell count decrease (27%), febrile neutropenia (7.6%), weight gain (3.8%), and weight loss (3.8%)ConclusionSequential administration of eribulin after the A/T-regimen provided no additional effect for LABC patients. Future research should continue to focus on identifying specific molecular biomarkers that can improve response rates.

scholarly journals Sequential dose-dense single agent chemotherapy for locally advanced breast cancer

2003 ◽  
Vol 11 (3) ◽  
pp. 149-149
Author(s):  
Svetislav Vrbic ◽  
Ivica Pejcic ◽  
Sladjana Filipovic ◽  
Stojan Radic
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Conservative Surgery ◽  
Advanced Breast ◽  
Dose Dense ◽  
Novel Concept ◽  
Single Agent Chemotherapy

Chemotherapy of breast cancer is still the area of intensive research. Based on mathematical model of tumor cell growth kinetics, articulated by Larry Norton, novel concept of chemotherapy in breast cancer was launched and it implies dose-densification of chemotherapy trough the use of sequential non cross-resistant single agents or regimens. The introduction of primary systemic chemotherapy (PST) improved the outcome of patients with locally advanced breast cancer (LABC). Simultaneous PST is the standard approach to patients with LABC nowadays. On the other hand, many studies using two most active cytotoxic drugs in primary breast cancer, anthracyclines and taxanes showed that sequential dose-dense single agent PST could be superior in terms of enhancing the rates of patients suitable for conservative surgery. In the light of this data, based on the results of the new clinical trials we will discuss merits and demerits of using sequential dose-dense single agent chemotherapy in LABC.

Identification of knowledge translation opportunities in the treatment of locally advanced breast cancer: Results of a national survey of physicians.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6585-6585
Author(s):  
Yanchini Rajmohan ◽  
Robyn Leonard ◽  
Sophie Hogeveen ◽  
Jalal Ebrahim ◽  
Dolly Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Knowledge Translation ◽  
Advanced Breast Cancer ◽  
Clinical Assessment ◽  
Current Practice ◽  
Practice Patterns ◽  
Response Rate ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Advanced Breast

6585 Background: Locally advanced breast cancer (LABC) accounts for only 10% of all breast cancers. While several guidelines and consensus statements exist, whether the current practice reflects these guidelines is unclear. We sought to survey the oncologists in Canada to assess current practice patterns and identify areas of targeted knowledge translation interventions (KTIs) in the treatment of LABC. Methods: 426 Canadian oncologists were surveyed with a 29 item survey-tool. They were subdivided into LABC experts (n=83) and non-experts (n=343). Physicians were removed from the survey if they identified that they were not involved in the treatment of breast cancer. The survey included demographic information as well as questions as to the current practice patterns utilized in the pathway of care for LABC patients. Level of discordance was calculated between the expert and non-expert responses using a z test. Results: 139 responses were obtained (48% response rate) from the non-experts and 51 responses were obtained from the experts (61% response rate). Areas of discordance in expert and non-expert survey included: frequency of clinical assessment during neoadjuvant therapy, methods for clinical assessment, radiographic re-evaluation post therapy, and assessment of receptor status (see Table). Conclusions: Several areas have been identified as targets for KTIs that may help to improve the quality and consistency of care of patients with LABC in Canada and may also have implications for improvements in resource utilization. [Table: see text]

A Randomized Trial of Chemotherapy with or without Estrogenic Recruitment in Locally Advanced Breast Cancer

1997 ◽  
Vol 83 (5) ◽  
pp. 829-833 ◽  
Author(s):  
Editta Baldini ◽  
Giovanni Gardin ◽  
Piergiorgio Giannessi ◽  
Fulvio Brema ◽  
Alessandra Camorriano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Advanced Breast ◽  
Phase Iii ◽  
Pathologic Features ◽  
Significant Difference

The present phase III trial was carried out to verify whether a kinetic recruitment induced by low doses of diethylstilbes-trol (DES) could increase the killing efficacy of chemotherapy in patients with locally advanced breast cancer. One-hundred and seventeen untreated patients with locally advanced breast cancer (stage IIIA/IIIB) were randomized to receive 3 courses of primary chemotherapy consisting of cyclophosphamide (600 mg/m2 i.v.), doxorubicin (50 mg/m2 i.v.) and fluorouracil (600 mg/m2 i.v.) (CAF) on day 1, or DES-CAF (DES, 1 mg orally days 1-3, CAF on day 4). The courses were repeated every 3 weeks. The patients who achieved an objective response were submitted to mastectomy followed by 3 courses of CAF alternated with 3 courses of CMF (cyclophosphamide, 600 mg/m2 i.v.; methotrexate, 40 mg/m2 i.v.; fluorouracil, 600 mg/m2 i.v.), with or without DES. The two treatment arms were well balanced in terms of clinical and pathologic features. There was no significant difference in response rates to induction chemotherapy between the two treatment arms (objective response rate, 63.3% for CAF and 56.1% for DES-CAF). Median overall survival was 49 and 47 months and median progression-free survival was 24 and 21 months for CAF and DES-CAF patients, respectively. Toxicity was not significantly different in the two groups, with the exception of leukopenia: DES chemotherapy was significantly more myelotoxic than the standard treatment, which resulted in a significant reduction in the actual dose intensity. In spite of the attractive experimental evidence, we conclude that so far there is no clinical advantage in the combination of estrogen and chemotherapy. Further research is needed to investigate different schedules of chemotherapy and hor-mones, or to test the possibility of combining various mitogens.

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