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Cancer Treatment Reviews Oct 2011Castration-refractory prostate cancer remains a therapeutic challenge even after introduction of docetaxel as first-line treatment. Castration-refractory prostate cancer... (Review)
Review
PURPOSE
Castration-refractory prostate cancer remains a therapeutic challenge even after introduction of docetaxel as first-line treatment. Castration-refractory prostate cancer cannot be cured by any available therapeutic option, and chemotherapy still needs to be considered palliative. The survival benefit is modest, and treating physicians are searching for alternative treatment options. Despite new drugs currently under investigation, some conventional and well known chemotherapeutic drugs are experiencing a renaissance. The development of anti-angiogenic approaches in cancer treatment has led to the development of metronomic dosing of conventional chemotherapeutic drugs including cyclophosphamide. The intention of this review is to evaluate the efficacy and toxicity of oral/metronomic cyclophosphamide in the treatment of patients with castration-refractory prostate cancer.
MATERIALS AND METHODS
A comprehensive literature search was performed in different databases using various key words. Relevant articles and references between 1962 and 2010 were reviewed and analyzed for data regarding the association between oral cyclophosphamide treatment and prostate cancer.
RESULTS
Oral cyclophosphamide is active in the treatment for castration-refractory prostate cancer even in patients treated with previous chemotherapy including docetaxel. It yields symptomatic and objective remissions. The side effects are usually grade 1-2 and easy to manage. Grade three to four side effects are less common.
CONCLUSIONS
Oral cyclophosphamide treatment for patients with castration-refractory prostate cancer deserves more attention and validation, and warrants further testing of various treatment combinations. Given the fact that castration-refractory prostate cancer includes an extremely heterogeneous group of patients with variability of tumor growth rates, the combination of cyclophosphamide with other active agents such as angiogenesis inhibitors and immunomodulatory compounds need to be explored.
Topics: Administration, Oral; Antineoplastic Agents, Alkylating; Castration; Cyclophosphamide; Humans; Male; Prostatic Neoplasms
PubMed: 21277093
DOI: 10.1016/j.ctrv.2010.12.006 -
Pediatric Blood & Cancer Sep 2019Metronomic chemotherapy transitioned from the bench to bedside in the early 2000s and since then has carved a niche for itself in pediatric oncology. It has been used... (Review)
Review
Metronomic chemotherapy transitioned from the bench to bedside in the early 2000s and since then has carved a niche for itself in pediatric oncology. It has been used solely or in combination with other modalities such as radiotherapy, maximum tolerated dose chemotherapy, and targeted agents in adjuvant, palliative, as well as maintenance settings. No wonder, the resulting medical literature is extremely heterogeneous. In this review, the authors review and synthesize the published literature in pediatric metronomics giving a glimpse of its history, varied applications, and evolution of this genre of chemotherapy in pediatric cancers. Limitations, future prospects, and grey areas are also highlighted.
Topics: Administration, Metronomic; Child; Humans; Neoplasms
PubMed: 31207063
DOI: 10.1002/pbc.27811 -
Cancer Communications (London, England) May 2020Real-world data of the CM regimen [cyclophosphamide (CTX) plus methotrexate (MTX)] in metronomic pattern for advanced breast cancer is limited to small-sample or...
BACKGROUND
Real-world data of the CM regimen [cyclophosphamide (CTX) plus methotrexate (MTX)] in metronomic pattern for advanced breast cancer is limited to small-sample or retrospective studies. This study was aimed to determine the effectiveness and safety of CM regimen in treating advanced breast cancer and to identify which patients are most likely to benefit from metronomic CM regimen.
METHODS
Patients with advanced breast cancer who received the metronomic CM regimen at least once between January 2009 and February 2019 in Sun Yat-sen University Cancer Center were included. Clinicopathological characteristics were collected. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier estimates. Characteristics between patients with PFS < 6 months and ≥6 months were compared using the Chi-square test. Univariate and multivariate Cox regression model was used to estimate the prognostic factors for PFS and OS.
RESULTS
A total of 186 patients were included. The median age and follow-up were 49 years and 13.3 months, respectively. Over 50% of the patients were estrogen receptor/progesterone receptor-positive, and 60.8% had been heavily treated (≥3 lines). The objective response rate was 3.8%, the disease control rate at 12 weeks was 41.4%, and the clinical benefit rate at 24 weeks was 31.2% (58/186). The median PFS was 4.0 months [95% confidence interval (CI): 3.6-4.7 months], the median duration of clinical benefit was 9.5 months (95% CI: 8.2-10.8 months), and the median OS was 26.8 months (95% CI: 20.9-37.7 months). Multivariate analysis for PFS revealed the CM regimen as maintenance therapy and no liver metastasis as favorable prognostic factors. Furthermore, patients without liver metastasis were more likely to have a PFS over 6 months than those with liver involvement (P = 0.022). Liver, lymph node, and brain metastases were unfavorable prognostic factors for OS. The CM regimen was well-tolerated without newly reported adverse events.
CONCLUSIONS
The CM regimen was effective in selected patients. In clinical practice, it would be better used as maintenance therapy and in patients without liver metastasis. Further follow-up investigation should be performed to examine its effect when used in combination with other treatments and determine predictive biomarkers.
Topics: Administration, Metronomic; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Data Analysis; Drug Administration Schedule; Humans; Kaplan-Meier Estimate; Methotrexate; Middle Aged; Multivariate Analysis; Retrospective Studies; Treatment Outcome
PubMed: 32390331
DOI: 10.1002/cac2.12029 -
Breast (Edinburgh, Scotland) Dec 2019Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged... (Observational Study)
Observational Study
Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3-10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8-11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3-15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Administration Schedule; Female; Humans; Middle Aged; Retrospective Studies; Survival Rate; Treatment Outcome
PubMed: 31470257
DOI: 10.1016/j.breast.2019.07.006 -
Anti-cancer Drugs Jan 2022Metronomic chemotherapy is a treatment option for metastatic breast cancer (MBC) patients who require prolonged disease control without cumulative toxicity. Data...
Metronomic chemotherapy is a treatment option for metastatic breast cancer (MBC) patients who require prolonged disease control without cumulative toxicity. Data available on the efficacy and tolerability of prolonged usage of metronomic therapy are limited. We analyzed patients with MBC, enrolled in a clinical trial, who obtained a prolonged clinical benefit for a duration of at least 12 months with vinorelbine 30 or 40 mg orally three times a week, cyclophosphamide 50 mg daily and capecitabine 500 mg three times a day (VEX regimen). The patients were treated at the European Institute of Oncology, Milan. We identified 67 MBC patients. The median age before starting the VEX regimen was 53 years. There were 59 patients (88%) who had hormone-receptors positive and HER2 negative BC. We had 37 patients who received VEX as the first-line treatment for MBC, while 30 patients were pretreated. The objective response rate was 49% (95% CI, 37-62). The median duration of VEX treatment after the first year was 14 months (min-max range 0.3-81.3 months). The progression-free survival at 3 years was 25.4% (95% CI, 15.7-36.2) and at 4 years was 18.5% (95% CI, 10.1-28.8 time 0 corresponds to 1 year after starting VEX). A total of 25 patients required a dose reduction, 7% of patients experienced G3 hand and foot syndrome. Metronomic VEX regimen can induce prolonged clinical benefit in MBC. On the basis of this long-term safety evaluation, there is no evidence of specific cumulative or delayed toxicities with metronomic chemotherapy.
Topics: Administration, Metronomic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Cyclophosphamide; Female; Humans; Middle Aged; Neoplasm Metastasis; Progression-Free Survival; Vinorelbine
PubMed: 34407044
DOI: 10.1097/CAD.0000000000001209 -
Journal of Clinical Oncology : Official... Mar 2023
Topics: Humans; Head and Neck Neoplasms; Immunotherapy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36669141
DOI: 10.1200/JCO.22.02398 -
Mathematical Biosciences Jun 2024Metronomic chemotherapy refers to the frequent administration of chemotherapeutic agents at a lower dose and presents an attractive alternative to conventional...
Metronomic chemotherapy refers to the frequent administration of chemotherapeutic agents at a lower dose and presents an attractive alternative to conventional chemotherapy with encouraging response rates. However, the schedule of the therapy, including the dosage of the drug, is usually based on empiricism. The confounding effects of tumor-endothelial-immune interactions during metronomic administration of drugs have not yet been explored in detail, resulting in an incomplete assessment of drug dose and frequency evaluations. The present study aimed to gain a mechanistic understanding of different actions of metronomic chemotherapy using a mathematical model. We have established an analytical condition for determining the dosage and frequency of the drug depending on its clearance rate for complete tumor elimination. The model also brings forward the immune-mediated clearance of the tumor during the metronomic administration of the chemotherapeutic agent. The results from the global sensitivity analysis showed an increase in the sensitivity of drug and immune-mediated killing factors toward the tumor population during metronomic scheduling. Our results emphasize metronomic scheduling over the maximum tolerated dose (MTD) and define a model-based approach for approximating the optimal schedule of drug administration to eliminate tumors while minimizing harm to the immune cells and the patient's body.
Topics: Humans; Administration, Metronomic; Neoplasms; Antineoplastic Agents; Models, Theoretical; Models, Biological; Maximum Tolerated Dose; Mathematical Concepts
PubMed: 38580078
DOI: 10.1016/j.mbs.2024.109186 -
Medical Oncology (Northwood, London,... Aug 2019The aim of our study is to investigate the efficacy of metronomic cyclophosphamide plus low dose of corticosteroids in advanced or metastatic castration-resistant...
Metronomic chemotherapy with cyclophosphamide plus low dose of corticosteroids in advanced castration-resistant prostate cancer across the era of taxanes and new hormonal drugs.
The aim of our study is to investigate the efficacy of metronomic cyclophosphamide plus low dose of corticosteroids in advanced or metastatic castration-resistant prostate cancer (CRPC) before, between, and after standard chemotherapy, such as docetaxel and cabazitaxel, and new hormonal treatments, such as abiraterone and enzalutamide. A retrospective analysis was performed on 37 patients. Cyclophosphamide was given orally 50 mg per day together with low dose of corticosteroids, namely dexametasone orally 1 mg per day or prednisone 10 mg per day. Seventeen patients (51%) showed a PSA decline≥ 50%. Median progression-free survival (PFS) and overall survival (OS) were 11 and 28 months, respectively. Median PFS and OS in the subgroup of patients with a PSA decline ≥ 50% were 14 and 35 months, respectively. Treatment was very well tolerated. We suggest that oral metronomic cyclophosphamide plus low dose of oral dexamethasone or prednisone may be a good and safe therapeutic option not only in those CRPC patients unfit for standard treatments but also in those heavily pre-treated patients.
Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Drug Administration Schedule; Glucocorticoids; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Survival Analysis; Taxoids; Treatment Outcome
PubMed: 31399784
DOI: 10.1007/s12032-019-1304-y -
Journal of Cancer Research and... 2020Head-and-neck cancer is the most common cancer in developing countries of Southeast Asia. Most of the patients present to the hospital in advanced stage and have a poor... (Observational Study)
Observational Study
Metronomic palliative chemotherapy in locally advanced, recurrent and metastatic head-and-neck cancer: A single-arm, retrospective study of a regional cancer center of North India (Asia).
BACKGROUND
Head-and-neck cancer is the most common cancer in developing countries of Southeast Asia. Most of the patients present to the hospital in advanced stage and have a poor prognosis. This study aims to evaluate the efficacy and toxicity profile of oral metronomic chemotherapy (MCT) in the form of methotrexate and celecoxib in locally advanced, recurrent and metastatic head-and-neck cancers.
MATERIALS AND METHODS
This was a single-arm retrospective observational study that included posttreatment patients with locally advanced, recurrent and metastatic disease in the year 2016 (January 1, to December 31, 2016). A total of 84 patients warranting palliative chemotherapy but not willing to take intravenous chemotherapy were included in the study. The oral MCT schedule consisted of oral celecoxib (200 mg twice daily) and oral methotrexate (15 mg/m/week). Response evaluation was done using the Response Evaluation Criteria in Solid Tumors criteria version 1.1, and toxicity profile was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Descriptive statistics and Kaplan-Meier analysis were performed.
RESULTS
Eighty-four patients, 68 males and 16 females, with a median age of 62 years (range: 35-80 years), were enrolled in the study to receive oral MCT. The Eastern Cooperative Oncology Group performance status was 0-1 in 62 patients and 2-3 in 22 patients. The primary sites of disease were buccal mucosa (18), tongue (22), tonsil (24), lower alveolus (7), hypopharynx (10), and soft palate (3). The best clinical response rate in post oral MCT was seen in the first 4 months (120 days). Objective response was observed in 67% of patients in the form of stable disease (56%) and partial response (11%). Disease progression was observed in 27% of patients. The median follow-up was 192 (6.4 months) days. The median estimated overall survival was 195 (6.5 months) days. The median estimated progression-free survival was 110 (3.6 months) days. Symptomatic relief with respect to pain was reported in about 75% of patients. Eighteen (21%) patients had Grade I-II mucosal reactions. Grade III-IV mucosal reactions were observed in five (6%) patients. Seventy-eight (93%) patients died at the end of the study at 1 year. Dose reduction was required in 15 (18%) patients.
CONCLUSION
Oral MCT using celecoxib and methotrexate is an effective, economical, and well-tolerated regimen with good pain control and low toxicity profile in patients with locally advanced, recurrent and metastatic head-and-neck cancer.
Topics: Administration, Metronomic; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Celecoxib; Female; Head and Neck Neoplasms; Humans; India; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Palliative Care; Prognosis; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Survival Rate
PubMed: 32719267
DOI: 10.4103/jcrt.JCRT_702_18 -
Cancer Journal (Sudbury, Mass.) 2015The clinical circumstance of treating spontaneous metastatic disease, after resection of primary tumors, whether advanced/overt or microscopic in nature, is seldom... (Review)
Review
A Decade of Experience in Developing Preclinical Models of Advanced- or Early-Stage Spontaneous Metastasis to Study Antiangiogenic Drugs, Metronomic Chemotherapy, and the Tumor Microenvironment.
The clinical circumstance of treating spontaneous metastatic disease, after resection of primary tumors, whether advanced/overt or microscopic in nature, is seldom modeled in mice and may be a major factor in explaining the frequent discordance between preclinical and clinical therapeutic outcomes where the trend is "overprediction" of positive results in preclinical mouse model studies. To evaluate this hypothesis, a research program was initiated a decade ago to develop multiple models of metastasis in mice, using variants of human tumor cell lines selected in vivo for enhanced spontaneous metastatic aggressiveness after surgical resection of established orthotopic primary tumors. These models have included breast, renal, and colorectal carcinomas; ovarian cancer (but without prior surgery); and malignant melanoma. They have been used primarily for experimental therapeutic investigations involving various antiangiogenic drugs alone or with chemotherapy, especially "metronomic" low-dose chemotherapy. The various translational studies undertaken have revealed a number of clinically relevant findings. These include the following: (i) the potential of metronomic chemotherapy, especially when combined with a vascular endothelial growth factor pathway targeting drug to successfully treat advanced metastatic disease; (ii) the development of relapsed spontaneous brain metastases in mice with melanoma or breast cancer whose systemic metastatic disease is successfully controlled for a period with a given therapy; (iii) foreshadowing the failure of adjuvant antiangiogenic drug-based phase III trials; (iv) recapitulating the failure of oral antiangiogenic tyrosine kinase inhibitors plus standard chemotherapy in contrast to the modest successes of antiangiogenic antibodies plus chemotherapy in metastatic breast cancer; and (v) revealing "vessel co-option" and absence of angiogenesis as a determinant of intrinsic resistance or minimal responsiveness to antiangiogenic therapy in lung metastases. Developing similar models of metastatic disease but involving mouse tumors grown in syngeneic immunocompetent mice may also prove useful for future translational studies of immune therapy-based treatments.
Topics: Administration, Metronomic; Angiogenesis Inhibitors; Animals; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cell Line, Tumor; Colorectal Neoplasms; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Humans; Kidney Neoplasms; Melanoma; Mice; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms; Neovascularization, Pathologic; Ovarian Neoplasms; Tumor Microenvironment; Vascular Endothelial Growth Factor A
PubMed: 26222079
DOI: 10.1097/PPO.0000000000000134