A phase II study of metronomic paclitaxel/cyclophosphamide/capecitabine followed by 5-fluorouracil/epirubicin/cyclophosphamide as preoperative chemotherapy for triple-negative or low hormone receptor expressing/HER2-negative primary breast cancer

Masuda, Norikazu; Higaki, Kenji; Takano, Toshimi; Matsunami, Nobuki; Morimoto, Takashi; Ohtani, Shoichiro; Mizutani, Masaki; Miyamoto, T.; Kuroi, Katsumasa; Ohno, Shinji; Morita, Satoshi; Toi, Masakazu

doi:10.1007/s00280-014-2492-y

Cited by 35 publications

(21 citation statements)

References 36 publications

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“…The clinical response rates were 90.0% and 93.9% in the intent-to-treat and per-protocol population, respectively, with a breast conservation rate of 72.7%. 60 These pCR rates were similar to response rates reported with conventional dose chemotherapy. Grade 3-4 adverse events included neutropenia (35%), leukopenia (25%), and hand-foot syndrome (8%).…”

Section: Ideal Agents and Drug Repositioningsupporting

confidence: 81%

“…Masuda and co-authors published a phase II study of metronomic-based preoperative chemotherapy for patients with triple-negative breast cancer (TNBC) or low hormone receptor expressing/HER2-negative primary breast cancer 60 (Table 1). In total, 40 patients with primary TNBC received four cycles of paclitaxel given as a weekly metronomic schedule (80 mg/m 2 on days 1, 8, and 15) plus metronomic cyclophosphamide (50 mg/day), and capecitabine (1,200 mg/m 2 daily), followed by four cycles of conventionally dosed chemotherapy with 5-FU (500 mg/m 2 ), epirubicin (100 mg/m 2 ), and cyclophosphamide (500 mg/m 2 ) every 3 weeks.…”

Section: Ideal Agents and Drug Repositioningmentioning

confidence: 99%

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Clinical overview of metronomic chemotherapy in breast cancer

2015

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Over 15 years ago, low-dose metronomic chemotherapy was shown to induce disease control in patients with advanced-stage breast cancer with a lower incidence of adverse events compared with conventional maximum tolerated dose chemotherapy. Good response rates have been seen in heavily pre-treated patients for whom limited treatment options are available. Most patients prefer oral therapy and metronomic chemotherapy is a convenient alternative in patients with advanced-stage disease in which minimal toxicity and good tumour control are the overall aims of treatment. The addition of metronomic protocols to standard neoadjuvant chemotherapy regimens has produced promising pathological complete response rates. Ongoing trials including the SYSUCC-001 trial in patients with triple-negative breast cancer and the IBCSG 22-00 trial that is assessing a cyclophosphamide-methotrexate maintenance regimen after standard adjuvant therapy in hormone receptor-negative disease, will clarify the value of adding this approach to conventional therapies. The low cost associated with metronomic chemotherapy represents an opportunity for the utilization of this treatment option, especially in developing countries, and poses a challenge for the launch of large trials sponsored by industry. Using breast cancer as the principal example, we discuss the key clinical advances in this area, including new trial design, appropriate patient and end point selection, as well as the evolving rationale for metronomic chemotherapy combinations.

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Section: Ideal Agents and Drug Repositioningsupporting

confidence: 81%

Section: Ideal Agents and Drug Repositioningmentioning

confidence: 99%

Clinical overview of metronomic chemotherapy in breast cancer

2015

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“…The reason behind this is that prominent adverse effects and absence of obvious benefits in the overall survival were found in clinical trials for simultaneously administered combination chemotherapy, despite a higher tumor response rate [41-43]. However, positive tumor response and low toxicity profiles were reported in recent Phase II clinical trials on low dose metronomic drug combinations [44, 45]. These mixed clinical results of drug combination therapy present an opportunity to nanocarrier-based approaches, which are able to mitigate the problems encountered by free drug combination therapies.…”

Section: Rationales and Strategies Of Nanocarrier-based Combinatiomentioning

confidence: 99%

Nanomedicine of synergistic drug combinations for cancer therapy – Strategies and perspectives

Zhang

Wong

Xue

et al. 2016

Journal of Controlled Release

300

166

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Nanomedicine of synergistic drug combinations has shown increasing significance in cancer therapy due to its promise in providing superior therapeutic benefits to the current drug combination therapy used in clinical practice. In this article, we will examine the rationale, principles, and advantages of applying nanocarriers to improve anticancer drug combination therapy, review the use of nanocarriers for delivery of a variety of combinations of different classes of anticancer agents including small molecule drugs and biologics, and discuss the challenges and future perspectives of the nanocarrier-based combination therapy. The goal of this review is to provide better understanding of this increasingly important new paradigm of cancer treatment and key considerations for rational design of nanomedicine of synergistic drug combinations for cancer therapy.

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“…Our group previously found that the Fu-Zheng-Xiao-Liu granules could inhibit the proliferation of drug-resistant MCF-7 cells and enhance the sensitivity of drug-resistant MCF-7 cells to a combination of chemotherapy drugs. The inhibitory effect of Fu-Zheng-Xiao-Liu granules on cancer cell proliferation was dependent on the down-regulation of multidrug resistance 1 (MDR1) and P-gp expression [17–20]. …”

Section: Discussionmentioning

confidence: 99%

Effect of Fu-Zheng-Xiao-Liu Granules on Expression of Human Epidermal Growth Factor Receptor 2 (HER-2) and Proliferation and Apoptosis of Breast Cancer Cell Line SKBR-3

Yue

Tian

et al. 2016

Med Sci Monit

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BackgroundPrevious research showed that granulized Fu-Zheng-Xiao-Liu has a significant effect on breast cancer. However, it remains unclear whether HER-2 plays a role in this anti-cancer effect.Material/MethodsSerum of male SD rats administered Fu-Zheng-Xiao-Liu granules (SF) was prepared and used to treat HER-2 positive breast cancer cell line SKBR-3. PBS and herceptin were used as negative and positive controls, respectively. MTT was used to detect the proliferation of SKBR-3 cells. Flow cytometry was used to measure the apoptosis of SKBR-3 cells. Western blot and immunofluorescence were used to measure the expression change of HER-2.ResultsSerum of male SD rats administered Fu-Zheng-Xiao-Liu granules had significantly reduced HER-2 expression at both mRNA level and protein level, significantly inhibited proliferation of SKBR-3 cells, and significantly increased apoptosis of SKBR-3 cells, compared to that of the blank control group or serum control group.ConclusionsFu-Zheng-Xiao-Liu granules affect proliferation and apoptosis through inhibition of HER-2 transcription and translation, providing an experimental basis for further study of the mechanism by which Fu-Zheng-Xiao-Liu granules affect breast cancer.

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A phase II study of metronomic paclitaxel/cyclophosphamide/capecitabine followed by 5-fluorouracil/epirubicin/cyclophosphamide as preoperative chemotherapy for triple-negative or low hormone receptor expressing/HER2-negative primary breast cancer

Abstract: Metronomic PCX followed by FEC chemotherapy was associated with a high pCR rate and low toxicity in TNBC patients. Further studies of this regimen in larger numbers of patients are warranted.

Cited by 35 publications

References 36 publications

Clinical overview of metronomic chemotherapy in breast cancer

Clinical overview of metronomic chemotherapy in breast cancer

Nanomedicine of synergistic drug combinations for cancer therapy – Strategies and perspectives

Effect of Fu-Zheng-Xiao-Liu Granules on Expression of Human Epidermal Growth Factor Receptor 2 (HER-2) and Proliferation and Apoptosis of Breast Cancer Cell Line SKBR-3

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