New cytotoxic agents and schedules for advanced breast cancer

The search for cytotoxic agents from marine natural products ultimately led to the production of eribulin, which is a synthetic macrocyclic ketone analog of halichondrin B. Eribulin binds to tubulin to induce mitotic arrest and gained approval in Japan in May 2010; it was approved by the US Food and Drug Administration in November 2010 and the European Medicines Agency in March 2011 and was reimbursed by the Taiwan National Health Insurance in December 2014 for patients with metastatic breast cancer who had received at least one anthracycline and one taxane. The recommended regimen for eribulin mesylate comprises intravenous administration of 1.4 mg/m2 (equivalent to 1.23 mg/m2 eribulin) over two to five minutes on days 1 and 8 of a three-week cycle. Since 2011, various clinical investigations of eribulin monotherapy with dose or schedule modifications, combined use with other antineoplastic therapeutics, or head-to-head comparisons with specific agents have been performed in the management of advanced breast cancer. Ethnic-specific data from Japan and Korea indicate higher rates (>85%) of grade 3 or 4 neutropenia. Some anecdotal evidence suggests that eribulin can shrink brain and retinal metastases, which warrants further detailed studies. In this review, current observations of the effects of eribulin monotherapy are summarized and eribulin-backbone combination (bio-) chemotherapy is investigated.

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New cytotoxic agents and schedules for advanced breast cancer

Seminars in Oncology ◽

10.1016/s0093-7754(01)90129-0 ◽

2001 ◽

Vol 28 (4) ◽

pp. 344-358 ◽

Cited By ~ 18

Author(s):

H BURSTEIN

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Advanced Breast ◽

Cytotoxic Agents

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Intensified local treatment and systemic therapy significantly increase time to progression and survival in patients with brain metastases from advanced breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.10536 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 10536-10536

Author(s):

R. Bartsch ◽

S. Muschitz ◽

C. Wenzel ◽

K. Roessler ◽

K. Dieckmann ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Advanced Breast Cancer ◽

Systemic Therapy ◽

Systemic Treatment ◽

Local Treatment ◽

Advanced Breast ◽

Cytotoxic Agents ◽

Time To Progression ◽

Metastatic Sites

10536 Background: Brain metastases (BM) have evolved from a rare to a frequently encountered event in advanced breast cancer (ABC) due to advances in palliative systemic treatment. Especially since the introduction of trastuzumab, different groups reported an increased incidence of BM. In this study, we retrospectively tried to establish factors predicting a prolonged survival in those patients (P). Methods: All P treated at our centre from 1994 to 2004 with whole brain radiotherapy for BM from ABC were included. Cerebral time to progression (cTTP) and overall survival (OS) were calculated using the Kaplan-Meier product limit method. A multivariate analysis (Cox regression) was performed to explore which factors are able to influence significantly cTTP and OS (metastatic sites [visceral versus non-visceral], Karnofsky performance score [KPS], age, intensified local treatment [boost irradiation, neuro-surgical resection], further palliative systemic treatment). Results: Overall 174 P, median age 51 years (y), range 27–76 y, were included. Median cTTP was 3 months (m), range 1–33+ m (95% CI 4.67–7.37). Median OS was 7 m, range 1–44 m (95% CI 5.08– 8.92). Factors significantly influencing cTTP were KPS (p = 0.0024), intensified local treatment (p < 0.0001), and palliative systemic treatment (P = 0.0003). Factors significantly influencing OS were intensified local treatment (p = 0.004), metastatic sites (p = 0.008), KPS (p = 0.006), and palliative systemic treatment (p < 0.001). Conclusion: As shown by the significant influence of metastatic sites, some P die from their advanced systemic disease situation before they would experience cerebral progression, in part explaining the influence of systemic treatment. In other individuals however, intensified local treatment and systemic treatment appear to influence both cTTP and OS significantly, implicating a direct influence of systemic therapy on BM. This might result from an impaired blood brain barrier around metastatic sites, making sufficient tissue concentrations of cytotoxic agents possible. No significant financial relationships to disclose.

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High-Dose Medroxyprogesterone Acetate (MPA) Treatment in Advanced Breast Cancer. A Review

Tumori Journal ◽

10.1177/030089167906500507 ◽

1979 ◽

Vol 65 (5) ◽

pp. 563-585 ◽

Cited By ~ 32

Author(s):

Fabrizio Ganzina

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Postmenopausal Women ◽

Medroxyprogesterone Acetate ◽

Response Rate ◽

Well Being ◽

Advanced Breast ◽

Cytotoxic Agents ◽

High Dose ◽

Early Results

Medroxyprogesterone acetate (MPA) when employed at high doses ≥ 500 ≤ 1000 mg/day i.m.) can produce objective remission with improved survival in about 30% of postmenopausal women with advanced breast cancer resistant to cytotoxic drugs and endocrine therapies. When administered to women not previously treated with chemotherapy, the objective remission response rate reached 40%. From available evidence, high dose MPA can be considered a useful agent in the treatment of advanced breast cancer in postmenopausal women with soft tissue, pulmonary, pleural or osseous involvement even when patients have become refractory to prior hormone and cytotoxic therapies. Early results suggest that the response rate can be increased in patients with estrogen and/or progesterone-positive receptors. It is note worthy that in a study conducted on postmenopausal women resistant to cytotoxic and/or hormonal drugs, the median duration of survival was 13.5 months, while CRs plus PRs did not reach the median at 24 months after starting MPA treatment. High dose MPA is essentially devoid of major side effects. Relief of pain, increase in appetite and body weight, and sense of well being are characteristic features of the improved quality of life under MPA treatment. However, a gluteal abscess (from 2% to 20% dose related) is the most frequent side effect. A promising area for future studies is combined therapy using hormonal and cytotoxic agents or alternating sequential combinations. Well-designed studies are needed to develop means for increasing the complete response rate and therefore survival. Recent studies of combined chemo-and hormonal (MPA) therapy have yielded objective tumor regressions of 53 to 80% with an increased rate of complete remissions and duration of response.

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