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Thoracic Cancer Aug 2023This single-arm prospective phase II trial was performed to assess the efficacy and safety of the dual oral metronomic vinorelbine and capecitabine (mNC) regimen in...
A phase II study of a doublet metronomic chemotherapy regimen consisting of oral vinorelbine and capecitabine in Chinese women with HER2-negative metastatic breast cancer.
BACKGROUND
This single-arm prospective phase II trial was performed to assess the efficacy and safety of the dual oral metronomic vinorelbine and capecitabine (mNC) regimen in women with HER2-negative metastatic breast cancer (MBC) in China.
METHODS
The mNC regimen was administered to the enrolled cases, including oral vinorelbine (VNR) 40 mg three times weekly (on days 1, 3 and 5 every week) and capecitabine (CAP) 500 mg three times a day, until disease progression or intolerable toxicity. The primary endpoint was the 1-year progression-free survival (PFS) rate. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR) and treatment-related adverse events (TRAEs). Stratified factors included treatment lines and hormone receptor (HR) status.
RESULTS
Between June 2018 and March 2023, 29 patients were enrolled into the study. The median follow-up time was 25.4 months (range, 2.0-53.8). In the entire group, the 1-year PFS rate was 54.1%. ORR, DCR and CBR were 31.0%, 96.6% and 62.1%, respectively. The mPFS was 12.5 months (range, 1.1-28.1). Subgroup analysis revealed that ORRs were 29.4% and 33.3% in first- and ≥second-line chemotherapy, respectively. ORRs were 29.2% (7/24) and 40.0% (2/5) for HR-positive MBC and metastatic triple-negative breast cancer (mTNBC), respectively. Grade 3/4 TRAEs were neutropenia (10.3%) and nausea/vomiting (6.9%).
CONCLUSIONS
The dual oral mNC regimen showed very good safety features and improved compliance without loss of efficacy in both first- and second-line treatments. The regimen also reached an excellent ORR in the mTNBC subgroup.
Topics: Humans; Female; Breast Neoplasms; Capecitabine; Vinorelbine; East Asian People; Prospective Studies; Vinblastine; Antineoplastic Combined Chemotherapy Protocols; Receptor, ErbB-2; Triple Negative Breast Neoplasms; Neoplasm Metastasis; Treatment Outcome
PubMed: 37402471
DOI: 10.1111/1759-7714.15011 -
Indian Journal of Cancer 2023Ovarian cancer is a leading cause of death from gynecological cancer in the world and in India. This study aims to evaluate the efficacy and toxicity profile of oral... (Observational Study)
Observational Study
BACKGROUND
Ovarian cancer is a leading cause of death from gynecological cancer in the world and in India. This study aims to evaluate the efficacy and toxicity profile of oral metronomic chemotherapy (MCT) in the form of etoposide, cyclophosphamide, and tamoxifen in recurrent and metastatic ovarian cancer.
METHODS
This was a retrospective observational study that included those post-treatment patients who had the recurrent or metastatic disease after completion of treatment in 2018 at Regional Cancer Centre, Bikaner, Rajasthan. Forty patients who were unfit for further intensive intravenous chemotherapy were included. The oral MCT constituted etoposide, cyclophosphamide, and tamoxifen. Descriptive statistics and Kaplan-Meier analyses were performed. Progression-free survival (PFS) and overall survival (OS) were assessed.
RESULTS
Forty women with a median age of 62 (range: 35-80) years were enrolled in the study to receive oral MCT. The Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) was 0-1 in 28 patients and 2-3 in 12 patients. The best clinical response rate post-oral MCT was seen in the first 4 months. Objective response was observed in 24 (60%) of patients in the form of stable disease (19, 47.5%) and partial response (5, 12.5%). Disease progression was observed in 10 (25%) of patients. The median follow-up was 6.4 months (4.5-9.2 months). The median estimated OS was 6.5 months. The median estimated PFS was 3.7 months. Nineteen (47.5%) patients had grade-I/II mucositis. Grade-III/IV mucositis were observed in 9 (22.5%) patients. Thirty-seven (92.5%) patients died at the end of the study at 1 year. Dose reduction was required in 15 (37.5%) patients.
CONCLUSION
Oral MCT was found to be an effective and well-tolerated regime with good symptomatic control and low-moderate toxicity profile in patients with relapsed and metastatic ovarian cancer. However, 22% of patients showed grade-III/IV thrombocytopenia.
Topics: Humans; Female; Adult; Middle Aged; Aged; Aged, 80 and over; Carcinoma, Ovarian Epithelial; Retrospective Studies; Etoposide; Mucositis; Administration, Metronomic; India; Cyclophosphamide; Ovarian Neoplasms; Tamoxifen; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37530237
DOI: 10.4103/ijc.IJC_143_20 -
Aging Apr 2016
Topics: Administration, Metronomic; Animals; Antineoplastic Agents; Female; Humans; Triple Negative Breast Neoplasms
PubMed: 27084985
DOI: 10.18632/aging.100947 -
Oncology Research and Treatment 2022Metronomic chemotherapy (MCT), termed sustained low-dose administration with minimal toxicity, is a new modality of conventional chemotherapy, a verified therapy... (Review)
Review
BACKGROUND
Metronomic chemotherapy (MCT), termed sustained low-dose administration with minimal toxicity, is a new modality of conventional chemotherapy, a verified therapy alternative, and has acquired significant recognition and interest in oncology. Numerous clinical trials of MCT in combination with other treatments, including targeted therapies, biologics, and endocrine therapy, are in progress to obtain better results.
SUMMARY
We comprehensively described the clinical benefits of MCT in combination with other treatments in different molecular subtypes of breast cancer and assessed the feasibility of its adoption in varying phases of treatment. Due to the promising preclinical and clinical investigations, it is expected that MCT in combination with other treatments will enhance the advantages of this strategy and apply it to clinical practice.
KEY MESSAGE
MCT, in combination with other therapeutic interventions, will fully exploit the benefits of this strategy, ushering in a new paradigm in oncology treatment and driving the transformation of cancer into a more manageable chronic disease using newly developed treatment approaches.
Topics: Humans; Female; Breast Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 35988534
DOI: 10.1159/000526481 -
International Journal of Molecular... Oct 2019Low dose metronomic chemotherapy (MC) is becoming a mainstream treatment for cancer in veterinary medicine. Its mechanism of action is anti-angiogenesis by lowering... (Review)
Review
Low dose metronomic chemotherapy (MC) is becoming a mainstream treatment for cancer in veterinary medicine. Its mechanism of action is anti-angiogenesis by lowering vascular endothelial growth factor (VEGF) and increasing trombospondin-1 (TSP1). It has also been adopted as a compassionate treatment in very advanced human cancer. However, one of the main limitations of this therapy is its short-term effectiveness: 6 to 12 months, after which resistance develops. pH-centered cancer treatment (pHT) has been proposed as a complementary therapy in cancer, but it has not been adopted or tested as a mainstream protocol, in spite of existing evidence of its advantages and benefits. Many of the factors directly or indirectly involved in MC and anti-angiogenic treatment resistance are appropriately antagonized by pHT. This led to the testing of an association between these two treatments. Preliminary evidence indicates that the association of MC and pHT has the ability to reduce anti-angiogenic treatment limitations and develop synergistic anti-cancer effects. This review will describe each of these treatments and will analyze the fundamentals of their synergy.
Topics: Administration, Metronomic; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Drug Synergism; Humans; Hydrogen-Ion Concentration; Neoplasms; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A
PubMed: 31683667
DOI: 10.3390/ijms20215438 -
Journal of Neuro-oncology Jan 2021Glioblastoma (GBM) has a survival rate of around 2 years with aggressive current standard of care. While other tumors have responded favorably to trials combining... (Review)
Review
INTRODUCTION
Glioblastoma (GBM) has a survival rate of around 2 years with aggressive current standard of care. While other tumors have responded favorably to trials combining immunotherapy and chemotherapy, GBM remains uniformly deadly with minimal increases in overall survival. GBM differ from others due to being isolated behind the blood brain barrier, increased heterogeneity and mutational burden, and immunosuppression from the brain environment and tumor itself.
METHODS
We have reviewed clinical and preclinical studies investigating how different doses (dose intense (DI) and metronomic) and timing of immunotherapy following TMZ treatment can eradicate tumor cells, alter tumor mutational burden, and change immune cells.
RESULTS
Recent clinical trials with standard of care (SoC), DI and metronomic TMZ regimes are no able to completely eradicate GBM. Elevated TMZ levels in DI treatment can overcome MGMT resistance but may result in hypermutation of surviving tumor cells. Higher levels of TMZ will also generate a higher degree of lymphopenia compared to SoC and metronomic regimes in preclinical studies.
CONCLUSION
The different levels of lymphopenia and tumor eradication discussed in this review suggest possible beneficial pairings between immunotherapy and TMZ treatment. Treatments resulting in profound lymphopenia will allow for expansion of vaccine specific T cells or of CAT T cells. Clinical and preclinical studies are currently comparing different combinations of TMZ and immunotherapy timing to treat GBM through a balance between tumor killing and immune cell expansion. More frequent immune monitoring time points in ongoing clinical trials are crucial for further development of these combinations.
Topics: Antineoplastic Agents, Alkylating; Brain Neoplasms; Cell Line, Tumor; Glioblastoma; Humans; Immunotherapy; Lymphopenia; Temozolomide; Treatment Outcome
PubMed: 32813186
DOI: 10.1007/s11060-020-03598-2 -
Cancer Medicine Aug 2019Patients with Non-Hodgkin lymphoma (NHL) treated by conventional chemotherapeutic drugs usually require a long recovery period. However, metronomic combination... (Comparative Study)
Comparative Study
Patients with Non-Hodgkin lymphoma (NHL) treated by conventional chemotherapeutic drugs usually require a long recovery period. However, metronomic combination chemotherapy (MCC) enhances therapeutic efficacy and decreases side effects in the treatment of NHL. In this study, we tested and compared the effects of metronomic chemotherapy (MC) using podophyllotoxin derivative etoposide (VP-16) alone and that of MCC using both VP-16 and everolimus (RAD001) in the treatment of NHL. Two types of NHL cells, OCI-LY-10 and SU-DHL-6, were employed for the experiments. Cell proliferation, apoptosis, and cell senescence were measured to test the effects of drugs in each experiment. In addition, the influences of MC and MCC on the cell cycle and autophagy pathway were evaluated to study the functional mechanisms behind their effects. Finally, we conducted analyses of the growth inhibitory effect and synergistic activity for different MCC. The results showed that MC using low-dose VP-16 alone demonstrated strong treatment effects in terms of inducing apoptosis, cell senescence, and reducing tumor cell proliferation, and this treatment also led to changes of the cell cycle. Compared with MC, MCC using VP-16 and RAD001 together demonstrated even stronger treatment effects, with both the cell cycle and autophagy-related proteins being affected. Considering the synergistic activity, our results showed the MCC of VP-16 48 hours + RAD001 24 hours is the optimal method for treating NHL.
Topics: Administration, Metronomic; Antineoplastic Combined Chemotherapy Protocols; Autophagy-Related Proteins; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drug Synergism; Etoposide; Everolimus; Gene Expression Regulation, Neoplastic; Humans; Lymphoma, Non-Hodgkin; Survival Analysis; Treatment Outcome
PubMed: 31218841
DOI: 10.1002/cam4.2364 -
Indian Journal of Pharmacology 2020Treatment of cancer is a major challenge even though the pathophysiology is becoming clearer with time. A number of new chemical entities are developed to target cancer... (Comparative Study)
Comparative Study Review
Treatment of cancer is a major challenge even though the pathophysiology is becoming clearer with time. A number of new chemical entities are developed to target cancer growth inhibition, but the targeted delivery of these products still needs novel research. This is of utmost importance not only for higher efficacy but also for a reduction in systemic toxicity and cost of treatment. Although multiple novel targets and molecules are being researched, most of them could not pass the regulatory approval process, due to low benefit-risk ratio and lack of target specificity. Failure of a majority of these drugs was in part due to their superiority claimed via surrogate markers. Despite these, currently, more than 100 chemotherapeutic agents are in practice. This review paper discusses in detail the molecular basis, drug discovery, and pros and cons over conventional treatment approaches of three novel approaches in cancer therapy, i.e., (i) antibody-drug conjugates, (ii) cancer immunotherapy, and (iii) metronomic chemotherapy. All the drugs developed using these three novel approaches were compared against the established treatment regimens in clinical trials with clinical end points, such as overall survival, progression-free survival, and quality of life.
Topics: Administration, Metronomic; Animals; Antineoplastic Agents; Drug Development; Humans; Immunoconjugates; Immunotherapy; Neoplasms; Progression-Free Survival; Quality of Life; Survival Rate
PubMed: 33283772
DOI: 10.4103/ijp.IJP_475_18 -
Taiwanese Journal of Obstetrics &... Jan 2020To analyze the response to dose-dense chemotherapy of weekly paclitaxel and 3-weekly carboplatin in recurrent ovarian cancer, and to report results of literature review. (Review)
Review
OBJECTIVE
To analyze the response to dose-dense chemotherapy of weekly paclitaxel and 3-weekly carboplatin in recurrent ovarian cancer, and to report results of literature review.
MATERIALS AND METHODS
Patients accepted weekly paclitaxel 80 mg/m on day 1, 8, 15 and carboplatin on day1 at area under curve (AUC) 6 every 21 days were reviewed for the response rate, progression-free survival, overall survival, and toxicity during January 2012 to April 2016 in Chang Gung Memorial Hospital at Linkou, Taiwan.
RESULTS
Sixteen patients with recurrent ovarian cancer, including 1 platinum-resistant, 7 partially platinum-sensitive, and 8 platinum-sensitive, accepted a median of 6 cycles of chemotherapy (range 3-10). The overall response rate (ORR) and complete response (CR) rate were 93.8%, and 62.5%, respectively. The median PFS of all patients were 10.9 months (range 4.3-40.5). The median time to response (TTR) was 29.0 days (range 19.6-38.4). The median disease-free survival (DFS) after CR was 5.6 months (range 1.2-34.2). Grade 3 at least toxicity included anemia (6.3%), neutropenia (50%), and thrombocytopenia (18.8%). Twenty-nine articles on phase I, II, III, or retrospective studies of dose-dense chemotherapy with weekly paclitaxel were reviewed.
CONCLUSION
This is the first report using Japanese Gynecologic Oncology Group 3016 protocol, weekly paclitaxel and 3-weely carboplatin, on recurrent ovarian cancer. The current study showed high ORR and CR with tolerable toxicities. Our study suggested dose-dense chemotherapy with paclitaxel, especially combining carboplatin created high efficacy probably by anti-angiogenesis. However, consolidation or maintenance therapy is needed to prolong DFS.
Topics: Adult; Antineoplastic Agents; Carboplatin; Drug Administration Schedule; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Paclitaxel; Progression-Free Survival; Retrospective Studies; Survival Rate; Taiwan; Treatment Outcome
PubMed: 32039795
DOI: 10.1016/j.tjog.2019.10.003 -
APMIS : Acta Pathologica,... Jul 2014Metronomic chemotherapy, which is continuously administered systemically at close to non-toxic doses, targets the endothelial cells (ECs) that are proliferating during... (Review)
Review
Metronomic chemotherapy, which is continuously administered systemically at close to non-toxic doses, targets the endothelial cells (ECs) that are proliferating during tumor angiogenesis. This leads to harmful effects of an even greatly increased number contiguous tumor cells. Although pre-clinical studies of angiogenesis-related EC features in vitro and of the anti-angiogenic and anti-tumor effects in vivo of metronomic chemotherapy have provided valuable insights, clinical trials with this type of therapy have been less successful in inhibiting tumor growth. One possible reason for the apparent disconnect between the pre-clinical and clinical outcomes is that most of the currently used experimental angiogenesis assays and tumor models are incapable of yielding data that can be translated readily into the clinical setting. Many of the assays used suffer from unintentional artifactual effects, e.g., oxidative stress in vitro, and inflammation in vivo, which reduces the sensitivity and discriminatory power of the assays. Co-treatment with an antioxidant or the inclusion of antioxidants in the vehicle often significantly affects the angiogenesis-modulating outcome of metronomic mono-chemotherapy in vivo. This 'metronomic chemotherapy vehicle factor' merits further study, as do the observations of antagonistic effects following metronomic treatment with a combination of standard chemotherapeutic drugs in vivo.
Topics: Administration, Metronomic; Angiogenesis Inhibitors; Animals; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Artifacts; Cell Line, Tumor; Cell Proliferation; Endothelial Cells; Humans; Inflammation; Mice; Neoplasms; Neovascularization, Pathologic; Oxidative Stress; Rats; Reactive Oxygen Species; Treatment Outcome
PubMed: 24164171
DOI: 10.1111/apm.12201