Resistance to metronomic chemotherapy and ways to overcome it

Martínez, María Carmen Riesco; Parra, Karla; Saluja, Ronak; Francia, Giulio; Emmenegger, Urban

doi:10.1016/j.canlet.2017.02.027

Cited by 30 publications

(21 citation statements)

References 79 publications

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“…Independent comparisons and discussions of neoadjuvant chemotherapy and adjuvant chemotherapy were not mentioned in our study. As we know, the resistance of chemotherapy does not change with or without surgery [49]. A large number of studies have confirmed that MDCI shows the same efficacy in neoadjuvant chemotherapy and adjuvant chemotherapy [24,50].…”

Section: Discussionmentioning

confidence: 93%

The efficacy and safety comparison of first-line chemotherapeutic agents (high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide) for osteosarcoma: a network meta-analysis

Zhang

et al. 2020

J Orthop Surg Res

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Background: Osteosarcoma, a primary malignant bone tumor derived from mesenchymal tissue, is the most common type of pleomorphic tumor that occurs in children and adolescents. The aim of this study was to compare the efficacy and safety of high-dose methotrexate (M), doxorubicin (D), cisplatin (C), and ifosfamide (I) in the management of osteosarcoma. Methods: Electronic databases including PubMed, Cochrane Library, and Embase database were searched for studies published from when the databases were established to July 13, 2019. The network meta-analysis was performed using software R 3.3.2 and STATA version 41.0 after demographic and outcome data extraction. The ranks based on probabilities of interventions for each outcome were performed. In addition, the consistency of direct and indirect evidence was assessed by node splitting. Results: The network meta-analysis results revealed that MDCI had a significant lower hazard risk of overall survival [MDCI vs MDC: HR = 0.74, 95% CrI (0.23, 0.87); MDCI vs DC: HR = 0.60, 95% CrI (0.16, 0.92)]. In addition, MDCI had a clearly longer progression-free survival time than that of DC [MDCI: HR = 0.88, 95% CrI (0.46, 0.98)]. No significant difference was detected in MDC and DC in OS, PFS, and AEs. The probabilities of rank plot showed that MDCI ranked first in OS (73.12%) and PFS (52.43%). DC was the best treatment in safety, ranked first (75.43%). Conclusions: MDCI showed its superiority among all chemotherapeutic agents in relation to efficacy and safety, followed by MDC. In addition, MDCI was associated with an increased risk of AEs. According to our analysis, DC was less effective but safer for MDC and MDCI.

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Section: Discussionmentioning

confidence: 93%

The efficacy and safety comparison of first-line chemotherapeutic agents (high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide) for osteosarcoma: a network meta-analysis

Zhang

et al. 2020

J Orthop Surg Res

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“…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]. A phase II trial with metronomic CTX and capecitabine in combination with bevacizumab showed a CBR of 68% ≥ 24 weeks and a mild toxicity profile in heavily pretreated MBC patients [18].…”

Section: Discussionmentioning

confidence: 99%

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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“…Different strategies to solve this problem were studied in preclinical and clinical models using thrombospondin 1 peptide ABT-510, VEGF pathway inhibitors, AKT inhibitor V, autophagy inducer rapamycin, autophagy inhibitor hydroxychloroquine and the tumor stroma modulating agents rofecoxib and pioglitazone. These therapeutic combinations may represent promising approaches to amplify MCT efficacy [102].…”

Section: Challenges and Future Directionsmentioning

confidence: 99%

Achievements and challenges in the use of metronomics for the treatment of breast cancer

Scharovsky

Rico

Mainetti

et al. 2020

Biochemical Pharmacology

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Resistance to metronomic chemotherapy and ways to overcome it

Cited by 30 publications

References 79 publications

The efficacy and safety comparison of first-line chemotherapeutic agents (high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide) for osteosarcoma: a network meta-analysis

The efficacy and safety comparison of first-line chemotherapeutic agents (high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide) for osteosarcoma: a network meta-analysis

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

Achievements and challenges in the use of metronomics for the treatment of breast cancer

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