Efficacy and safety of low-dose metronomic chemotherapy with capecitabine in heavily pretreated patients with metastatic breast cancer

115 Background: The purpose of this study is to determine the efficacy and safety of metronomic chemotherapy with all-oral combination of low-dose etoposide/capecitabine in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and/or taxanes. Methods: From June 2008 to April 2012, 22 women with MBC were enrolled and 16 patients were evaluable for toxicity and response. Treatment consisted of capecitabine (1,400 mg/m2 daily, taken in 2 oral doses) on days 1-14 and oral etoposide ( 30 mg/m2 daily ) on days 1-7 . Cycles were repeated every 3 weeks unless disease progression or unacceptable toxicity occurred or patient consent was withdrawn. The primary endpoint was clinical benefit rate (CR + PR + SD≥24 weeks); secondary endpoint was toxicity and time to progression (TTP). Tumor response was evaluated by RECIST criteria, and adverse events were evaluated by NCI-CTC AE v3.0. Results: Sixteen patients were included and received 145 cycles of chemotherapy, with a median of 7 cycles (range, 2-26 cycles). One of the 16 patients had partial response (PR 6.25%), 10 showed stable disease (SD 62.5%) and 5 had progression of disease (PD 31.25%), with a clinical benefit rate of 50% (CR + PR + SD≥24 weeks). Median TTP was 5.0 months (range, 1.5-20 months), and mean TTP was 6.06 months. Adverse effects were mild, and the main adverse effects were leucopenia (13%) and fatigue (13%). All patients are survival till now. Conclusions: An all-oral combination of low-dose etoposide plus capecitabine is a new regimen and has showed effective in treating MBC patients and can be well tolerated. It’s very economic compared with most other schedules today. It is worthy of further study on a large scale, especially in the developing countries.

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Paclitaxel activity in heavily pretreated breast cancer: a National Cancer Institute Treatment Referral Center trial.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.8.2056 ◽

1995 ◽

Vol 13 (8) ◽

pp. 2056-2065 ◽

Cited By ~ 85

Author(s):

J S Abrams ◽

D A Vena ◽

J Baltz ◽

J Adams ◽

M Montello ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Progressive Disease ◽

Overall Response Rate ◽

Metastatic Breast ◽

Investigational Drug ◽

Single Institution ◽

Doxorubicin Treatment ◽

Heavily Pretreated ◽

Pretreated Patients

PURPOSE To provide paclitaxel, an investigational drug at the inception of this study, to women with chemotherapy-refractory metastatic breast cancer and to evaluate response and toxicity in these patients. PATIENTS AND METHODS Two hundred sixty-seven patients with progressive disease (PD) following at least two chemotherapy regimens for metastatic breast cancer and a contraindication to further doxorubicin treatment received paclitaxel either at 175 mg/m2 intravenously (IV) over 24 hours or at 135 mg/m2 if they had prior irradiation to 30% of marrow-bearing bone or a cumulative dose of mitomycin > or = 20 mg/m2. RESULTS In a subgroup of patients (n = 172) with measurable disease, four complete responses (CRs) and 36 partial responses (PRs) occurred, for an overall response rate of 23% (95% confidence interval [CI], 17% to 30%). No differences in response rates were noted according either to the number of prior chemotherapy regimens received or to whether patients were considered refractory to doxorubicin. The dose and schedule used in this trial resulted in febrile neutropenia in 45% of patients and a hospitalization rate of 49%. CONCLUSION Paclitaxel's activity in this multiinstitutional trial in heavily pretreated patients confirms the encouraging results attained in single-institution trials. Although at this dose and schedule paclitaxel may be considered too myelosuppressive for palliative care, supportive measures such as colony-stimulating factors and antibiotics were not used prophylactically. Current research efforts are focusing on whether paclitaxel's activity against breast cancer is dose- and/or schedule-dependent, and on what role it has in patients with less advanced disease.

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Phase II Study of Temsirolimus (CCI-779), a Novel Inhibitor of mTOR, in Heavily Pretreated Patients With Locally Advanced or Metastatic Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2005.66.130 ◽

2005 ◽

Vol 23 (23) ◽

pp. 5314-5322 ◽

Cited By ~ 347

Author(s):

Stephen Chan ◽

Max E. Scheulen ◽

Stephen Johnston ◽

Klaus Mross ◽

Fatima Cardoso ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Adverse Events ◽

Dose Level ◽

Locally Advanced ◽

Metastatic Breast ◽

Heavily Pretreated ◽

Pretreated Patients ◽

Grade 3 ◽

Time To Tumor Progression

Purpose In this study, two doses of temsirolimus (CCI-779), a novel inhibitor of the mammalian target of rapamycin, were evaluated for efficacy, safety, and pharmacokinetics in patients with locally advanced or metastatic breast cancer who had been heavily pretreated. Patients and Methods Patients (n = 109) were randomly assigned to receive 75 or 250 mg of temsirolimus weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, adverse events, and pharmacokinetics of temsirolimus. Results Temsirolimus produced an objective response rate of 9.2% (10 partial responses) in the intent-to-treat population. Median time to tumor progression was 12.0 weeks. Efficacy was similar for both dose levels but toxicity was more common with the higher dose level, especially grade 3 or 4 depression (10% of patients at the 250-mg dose level, 0% at the 75-mg dose level). The most common temsirolimus-related adverse events of all grades were mucositis (70%), maculopapular rash (51%), and nausea (43%). The most common, clinically important grade 3 or 4 adverse events were mucositis (9%), leukopenia (7%), hyperglycemia (7%), somnolence (6%), thrombocytopenia (5%), and depression (5%). Conclusion In heavily pretreated patients with locally advanced or metastatic breast cancer, 75 and 250 mg temsirolimus showed antitumor activity and 75 mg temsirolimus showed a generally tolerable safety profile.

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