Metastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of response

Perroud, Herman A.; Alasino, Carlos María; Rico, María José; Mainetti, Leandro E.; Queralt, Francisco; Pezzotto, Stella Maris; Rozados, Viviana R.; Scharovsky, O. Graciela

doi:10.1007/s00280-015-2947-9

Cited by 39 publications

(39 citation statements)

References 36 publications

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“…Orlando et al [15] showed in a long-term follow-up study that metronomic CTX/MTX was feasible and provided a prolonged clinical benefit (CB) in 16% of patients without cumulative toxicity despite prolonged use. In a prospective, non-randomized, phase II clinical trial, Perroud et al [12] showed in patients with advanced breast cancer a CB of 55% (11/20) at 24 weeks after the beginning of treatment with metronomic CTX and celecoxib, a selective cyclooxygenase-2 inhibitor. Moreover, serum concentration of vascular endothelial growth factor (VEGF) decreased and soluble vascular endothelial growth factor receptor 2 (sVEGFR-2) increased during treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Circulating endothelial cells (CECs) increased in patients with CB at the time of progression. Perroud et al [12] postulated baseline VEGF and VEGF/sVEGFR-2 to be potential predictive biomarkers of response, and CECs of follow-up, in metronomic chemotherapy. Because of the well-known anti-angiogenic effects of LDMC, combinations with other agents targeting VEGF were evaluated [16,17].…”

Section: Discussionmentioning

confidence: 99%

“…Over the last decade, clinicians have begun to consider introducing LDMC much earlier into the treatment plan [8,9]. In comparison with conventional chemotherapy, the lower doses of LDMC may induce fewer side effects [10,11,12,13], which may lead to a lower rate of discontinuation due to side effects such as myelosuppression [10]. In this explorative retrospective analysis, the therapeutic effects and the side effects of LDMC with cyclophosphamide (CTX) and methotrexate (MTX) in patients with MBC were examined.…”

Section: Introductionmentioning

confidence: 99%

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Explorative Analysis of Low-Dose Metronomic Chemotherapy with Cyclophosphamide and Methotrexate in a Cohort of Metastatic Breast Cancer Patients

Krajnak¹,

Battista²,

Brenner³

et al. 2018

Breast Care

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Background: Low-dose metronomic chemotherapy (LDMC) is increasingly used in metastatic breast cancer (MBC). In this retrospective analysis, we examined the therapeutic effects and side effects of LDMC in a cohort of MBC patients. Methods: Patients with MBC were included when LDMC with oral cyclophosphamide (CTX) and methotrexate (MTX) was administered between 2009 and 2015. The primary endpoint was disease control rate (DCR) ≥ 24 weeks after the start of LDMC. Secondary endpoints were duration of progression-free survival (PFS), rates of discontinuation due to side effects, and DCR with regard to subgroups. Results: Retrospective data of 35 patients were available for this analysis. 31% patients achieved DCR. The median PFS was 12 weeks. 9% of patients discontinued LDMC due to adverse events. DCR was 37% in the first 2 lines and 25% in further lines of therapy. 22% of patients with multiple metastases and 35% with ≤2 different metastatic sites achieved DCR. DCR was achieved in 33% of hormone receptor(HR)-positive patients and 27% of HR-negative patients. Conclusion: The DCR of 31% is in line with the results of previous phase II studies. LDMC was well tolerated. Subgroup analysis was not able to identify a group in which LDMC was more efficient.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Explorative Analysis of Low-Dose Metronomic Chemotherapy with Cyclophosphamide and Methotrexate in a Cohort of Metastatic Breast Cancer Patients

Krajnak¹,

Battista²,

Brenner³

et al. 2018

Breast Care

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“…More details about individual patient's characteristics are available in Supplementary Table 1. Details regarding response were previously described by Perroud et al [15,16]. Briefly, the treatment combination showed a good therapeutic profile, being clinical benefit the most important clinical outcome, with a very low toxicity profile.…”

Section: Resultsmentioning

confidence: 99%

“…Details about the clinical study have been described elsewhere [15,16]. This study has been reviewed and approved by the Bioethics Committee of the School of Medical Sciences of the National University of Rosario (#5732/2007) and by ANMAT (National Administration of Drugs, Foods and Medical Devices), the Argentine regulatory agency (#4596/09).…”

Section: Methodsmentioning

confidence: 99%

Quality of Life in Patients with Metastatic Breast Cancer Treated with Metronomic Chemotherapy

et al. 2016

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Aim:The objective of the study was to detect changes in quality of life (QoL) in metastatic breast cancer patients treated with metronomic chemotherapy with daily low doses of cyclophosphamide and celecoxib. Material & methods: Patients included in a Phase II trial, treated with metronomic cyclophosphamide and celecoxib were included in the QoL study. Assessment of QoL was carried out every 2 months by the Functional Assessment of Cancer Therapy Breast (FACT-B) questionnaire, Brief Pain Inventory and Eastern Cooperative Oncologic Group scale. Data were analyzed at three time points: baseline (BL); middle of treatment (MT); and end of treatment (ET). Results: A total of 20 patients were included. All patients were heavily pretreated. Treatment showed a good and safe therapeutic profile. With FACT-B questionnaire, no significant differences were observed during the response period (BL-MT). However, a significant increase was observed in the Emotional wellbeing and Additional concerns axes, when the last time point was included in the analysis (BL-MT-ET). A significant decrease in the proportion of patients with pain was found when comparing BL with ET (p = 0.046). The assessment with Eastern Cooperative Oncologic Group scale showed that 26.7% (4/15) of the patients improved their functional status and 40% (6/15) showed no changes, while 33.3% (5/10) worsened it. Conclusion: Patients treated metronomically for several months did not worsen their QoL. A high proportion of patients showed improvement or no changes and there were less patients with pain at the end of the treatment. The quality of life (QoL) is a very common term used in different fields of human health. Therefore, it is very difficult to find a unique definition since it could be related to all aspects of human life [1].In an attempt to define it, it can be said that it is "the perfect balance between well-being and distress" [2,3]. The concept of adaptation to chronic disease is different but it is related to that of QoL; adaptation is the process whereby individuals use conscious awareness and choice to create new human environmental integration [4,5]. Both are good indicators of the evolution of psychological features of cancer patients at different stages of the disease [6]. In oncology QoL is centered in patients' health, and refers to all aspects (general, social, personal, emotional, among others) of 1234RESEaRch aRticlE Perroud, Alasino, Rico et al. future science group the subject and their relationship to the cancer disease and its treatment.The presence of pain is a very complex aspect related to QoL, and it is one of the most difficult symptoms to evaluate and to treat; in many cases pain is caused by the pressure that the tumor exerts on bones and/or nerves, and also it could be caused by cancer treatment. One of the barriers in pain treatment is the inadequate measurement and assessment of pain. An optimal management includes the evaluation of intensity, characteristics and interference with daily habits and life style [7,8].The meas...

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A Phase 1 Dose‐Escalation Study of Low‐Dose Metronomic Treatment With Novel Oral Paclitaxel Formulations in Combination With Ritonavir in Patients With Advanced Solid Tumors

Weger

Vermunt

Stuurman

et al. 2020

Clinical Pharm in Drug Dev

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ModraPac001 (MP1) and ModraPac005 (MP5) are novel oral paclitaxel formulations that are coadministered with the cytochrome P450 3A4 inhibitor ritonavir (r), enabling daily low-dose metronomic (LDM) treatment. The primary aim of this study was to determine the safety, pharmacokinetics and maximum tolerated dose (MTD) of MP1/r and MP5/r. The second aim was to establish the recommended phase 2 dose (RP2D) as LDM treatment. This was an open-label phase 1 trial. Patients with advanced solid tumors were enrolled according to a classical 3+3 design. After initial employment of the MP1 capsule, the MP5 tablet was introduced. Safety was assessed using the Common Terminology Criteria for Adverse Events version 4.02. Pharmacokinetic sampling was performed on days 1, 2, 8, and 22 for determination of paclitaxel and ritonavir plasma concentrations. In this study, 37 patients were treated with up to twice-daily 30-mg paclitaxel combined with twice-daily 100-mg ritonavir (MP5/r 30-30/100-100) in 9 dose levels. Dose-limiting toxicities were nausea, (febrile) neutropenia, dehydration and vomiting. At the MTD/RP2D of MP5/r 20-20/100-100, the maximum paclitaxel plasma concentration and area under the concentration-time curve until 24 hours were 34.6 ng/mL (coefficient of variation, 79%) and 255 ng • h/mL (coefficient of variation, 62%), respectively. Stable disease was observed as best response in 15 of 31 evaluable patients. Based on these results, LDM therapy with oral paclitaxel coadministrated with ritonavir was considered feasible and safe. The MTD and RP2D were determined as MP5/r 20-20/100-100. Further clinical development of MP5/r as an LDM concept, including potential combination treatment, is warranted.

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Metastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of response

Abstract: Background: Preclinical results showing therapeutic effect and low toxicity of metronomic

Cited by 39 publications

References 36 publications

Explorative Analysis of Low-Dose Metronomic Chemotherapy with Cyclophosphamide and Methotrexate in a Cohort of Metastatic Breast Cancer Patients

Explorative Analysis of Low-Dose Metronomic Chemotherapy with Cyclophosphamide and Methotrexate in a Cohort of Metastatic Breast Cancer Patients

Quality of Life in Patients with Metastatic Breast Cancer Treated with Metronomic Chemotherapy

A Phase 1 Dose‐Escalation Study of Low‐Dose Metronomic Treatment With Novel Oral Paclitaxel Formulations in Combination With Ritonavir in Patients With Advanced Solid Tumors

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