Metronomic oral combination chemotherapy with capecitabine and cyclophosphamide: a phase II study in patients with HER2-negative metastatic breast cancer

Yoshimoto, Masataka; Takao, Shintaro; Hirata, Masaru; Okamoto, Yasushi; Yamashita, Sumio; Kawaguchi, Yoshihiro; Takami, Makoto; Furusawa, Hidemi; Morita, Satoshi; Abe, Chigusa; Sakamoto, Junichi

doi:10.1007/s00280-012-1826-x

Cited by 51 publications

(28 citation statements)

References 24 publications

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“…In summary, a total of 818 patients received MCT, 383 patients received MCT combined with other therapies, and 159 patients could not be grouped (see detailed MCT schedules and registration numbers in S1 Table). It should be noted that data about tumor response from 5 studies were omitted due to the lack of adherence to the RECIST criteria [3,7,25,28,34], so were AEs data for lacking adherence to the NCICTC guidelines [18,28,35–39]. The 2 trials in which patients were divided into two separate groups (MCT vs. MCT in combination with other therapy) did not present data separately for each individual group and therefore data from those studies were excluded from the subgroup analysis [25,28].…”

Section: Resultsmentioning

confidence: 99%

The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis

Liu

Liang

et al. 2017

PLoS ONE

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PurposeThe current meta-analysis aimed to summarize the available evidence for the efficacy and serious adverse events (AEs) associated with use of metronomic chemotherapy (MCT) in patients with metastatic breast cancer (MBC).MethodElectronic databases (PubMed, EMBASE database, Web of Knowledge, and the Cochrane database) were systematically searched for articles related to the use of MCT in MBC patients. Eligible studies included clinical trials of MBC patients treated with MCT that presented sufficient data related to tumor response, progression-free survival (PFS), overall survival (OS), and grade 3/4 AEs. A meta-analysis was performed using a random effects model.ResultsThis meta-analysis consists of 22 clinical trials with 1360 patients. The pooled objective response rate and clinical benefit rate of MCT were 34.1% (95% CI 27.4–41.5) and 55.6% (95% CI 49.2–61.9), respectively. The overall 6-month PFS, 12-month OS, and 24-month OS rates were 56.8% (95% CI 48.3–64.9), 70.3% (95% CI 62.6–76.9), and 40.0% (95% CI 30.6–50.2), respectively. The pooled incidence of grade 3/4 AEs was 29.5% (95% CI 21.1–39.5). There was no statistically significant difference observed in any endpoint between subgroups defined by concomitant anti-cancer therapies or chemotherapy regimens. After excluding one controversial study, we observed a trend showing lower toxicity rates with the use of MCT alone compared to use of MCT with other anti-cancer therapies (P = 0.070).ConclusionsMetronomic chemotherapy may be effective for use in patients with metastatic breast cancer. MCT used alone is possibly equally effective and less toxic than combination therapies. Well-designed RCTs are needed to obtain more evidence.

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Section: Resultsmentioning

confidence: 99%

The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis

Liu

Liang

et al. 2017

PLoS ONE

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“…[9] The various drugs used with substantial clinical effects are oral cyclophosphamide, capecetabine, methotrexate, etoposide, vinorelbine etc. [1011121314] This strategy has some definite advantages over conventional pulsed course chemotherapy like its lesser toxicity profile, better compliance and suitability for patients otherwise not fit for full dose chemotherapy. Metronomic oral cyclophosphamide (Cy) has been extensively studied and widely used for various advanced and metastatic solid tumors with variable results.…”

Section: Discussionmentioning

confidence: 99%

“…It is used singly or in combination with various chemotherapeutic and targeted agents for diverse malignancies like metastatic renal cell carcinoma, multiple myeloma, breast, prostate, head and neck and GI malignancies. [10111213] The heterogenecity of chemotherapy combinations used in above studies has made it difficult to objectively evaluate the additional value of the metronomic administration of cyclophosphamide. The combination of cyclophosphamide with celecoxib for heavily pretreated gastrointestinal tumors is found to be feasible, well tolerated and associated with a promising antitumor activity both demonstrated by pharmacodynamic markers and clinical parameters.…”

Section: Discussionmentioning

confidence: 99%

Metastatic primary duodenal adeno-carcinoma responding to metronomic oral cyclophosphamide chemotherapy

Bandyopadhyay¹,

Das²,

Kundu³

2014

Indian J Palliat Care

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Primary adenocarcinoma of duodenum is a very rare tumour with a prevalence of only 0.3 to 1% of among all the tumours of gastrointestinal tracts. Localised tumours, if resected have good prognosis but those with metastates entails a poor prognosis, where generally palliation may be the only feasible option. Low dose continous cytotoxic treatment or metronomic chemotherapy prevents neoangiogenesis and chemoresistance thereby, provides excellent symptom relief and palliation in many advanced heavily pretreated solid malignancies. It offers as an affordable, less toxic therapy with moderate to good efficacy. Here we report a case of a 52 year female who, presented with history of maleana, pallor and pedal edema for last 2 months. Her performance status was poor (KPS 40) and she had enlarged left supraclavicular lymph node, palpable liver and vague mass in paraumbilical region. Upper GI endoscopy revealed large ulceroproliferative growth in the D2 segment and HPE showed moderately differentiated adenocarcinoma. CT scan revealed paratracheal and retroperitoneal lymphadenopathy and bone scan revealed vertebral metastasis. Patient received oral cyclophosphamide and hematinic and vitamin support, along with radiation to spine. There was near complete clinical response, and progression free period of about 32 weeks. Thus, single agent cyclophosphamide in the present case provided near total clinical response and prolonged period of freedom from disease progression with excellent palliation of symptoms. Hence in patient of advanced and metastatic small bowel cancer, with poor performance status metronomic therapy with single agent cyclophosphamide may provide viable option both for treatment and palliation.

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“…The purpose of these regimens is to achieve longer survival with fewer side effects. For HER2 negative breast cancers, Yoshimoto et al [60] found that TNBC patients had an overall response rate of 44.4% with a progression-free survival of 10.7 months; and for ER/PR-positive patients, the response rates were 46.4% and 12.2 months PFS. It has been postulated that this treatment modality induces endothelial cells apoptosis, resulting in angiogenesis impairment [60].…”

Section: Metastatic Diseasementioning

confidence: 99%

“…For HER2 negative breast cancers, Yoshimoto et al [60] found that TNBC patients had an overall response rate of 44.4% with a progression-free survival of 10.7 months; and for ER/PR-positive patients, the response rates were 46.4% and 12.2 months PFS. It has been postulated that this treatment modality induces endothelial cells apoptosis, resulting in angiogenesis impairment [60]. This is an interesting approach that merits further investigation considering the lack of durability in the patient response to chemotherapy seen in TNBC.…”

Section: Metastatic Diseasementioning

confidence: 99%

Triple Negative Breast Cancer: A Review of Clinicopathologic Characteristics And Treatment Options

Porro

Mrazek

Washington

et al. 2014

TOBCANJ

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Breast cancer is the second leading cause of cancer death in women. Approximately 15-20% are triple negative breast cancer (TNBC: no protein expression of estrogen receptor, progesterone receptor, nor human epidermal growth factor receptor 2), representing one of the most challenging molecular subtypes of breast cancer. TNBC encompasses a heterogenous group of breast cancers that are not generally responsive to targeted therapies for hormone and growth factor receptors. Compared to their hormone receptor-positive counterparts, TNBC cases are associated with poor prognosis, worse overall survival and earlier recurrence. The purpose of this review is to describe the clinicopathologic features, molecular variants, associations with the BRCA genes, and therapeutic approaches for TNBC. New TNBC-targeted drug therapies are currently under investigation and include poly-ADP-ribose polymerase (PARP) inhibitors, platinum-based drugs, anti-epidermal growth factor receptor (EGFR) inhibitors, and anti-vascular endothelial growth factor receptor (VEGF) inhibitors. Both clinical trials and basic research are needed to further our understanding of the best treatment options for patients with TNBC.

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Metronomic oral combination chemotherapy with capecitabine and cyclophosphamide: a phase II study in patients with HER2-negative metastatic breast cancer

Abstract: Oral XC is an effective first- or second-line therapy for MBC, demonstrating high activity in both luminal A and triple-negative disease with few severe side effects. This metronomic oral combination chemotherapy could be beneficial for the treatment of HER2-negative MBC.

Cited by 51 publications

References 24 publications

The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis

The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis

Metastatic primary duodenal adeno-carcinoma responding to metronomic oral cyclophosphamide chemotherapy

Triple Negative Breast Cancer: A Review of Clinicopathologic Characteristics And Treatment Options

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