Did you mean: 'metronomic chemotherapy'
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Frontiers in Veterinary Science 2024Veterinary oncology has experienced significant evolution over the last few decades, with chemotherapy being currently applied to several neoplasms with therapeutic... (Review)
Review
Veterinary oncology has experienced significant evolution over the last few decades, with chemotherapy being currently applied to several neoplasms with therapeutic success. Traditionally, chemotherapy protocols are based on classic cytostatic drugs under the concept of maximum tolerated dose (MTD), which has been associated with a greater risk of toxicity and resistance. Thus, new therapeutic alternatives have emerged, such as metronomic chemotherapy (MC), introducing a new paradigm in cancer treatment. MC consists of administering low doses of chemotherapy drugs continuously over a long period of time, modulating the tumour microenvironment (TME) due to the combination of cytotoxic, antiangiogenic and immunomodulatory effects. This multi-targeted therapy has been described as a treatment option in several canine and feline cancers since 2007, with positive results already published in the literature, particularly in mammary carcinomas and soft tissue sarcomas in dogs. The aim of this review article is to describe the current knowledge about the use of MC in small animal oncology, with emphasis on its mechanisms of action, the most commonly used drugs and clinical outcome.
PubMed: 38903691
DOI: 10.3389/fvets.2024.1397376 -
Wounds : a Compendium of Clinical... May 2024Marjolin ulcer (MU) is an aggressive cutaneous malignancy that commonly occurs in those with a chronic wound such as post-burn scar. (Review)
Review
BACKGROUND
Marjolin ulcer (MU) is an aggressive cutaneous malignancy that commonly occurs in those with a chronic wound such as post-burn scar.
CASE REPORT
A 20-year-old male who sustained a flame burn over the scalp at 3 months of age developed a nonhealing ulcer over the burn scar 20 years later, which was treated with adequate surgical margins with adjuvant mold brachytherapy. Two months after completion of that treatment, he developed parotid nodal metastasis with positron emission tomography (PET)-positive bilateral cervical, supraclavicular, right suboccipital, and mesenteric lymph nodes that were treated with concurrent chemoradiation. One month later, the patient developed an ulcerative lesion involving the left parotid region with PET showing infiltration of the parotid gland, but with resolution of other previous sites of uptake. The patient was treated surgically with radical parotidectomy with elective neck dissection and reconstruction with locoregional flap. At 6-month follow-up, the patient developed extensive locoregional recurrence and distant metastasis and was started on oral metronomic therapy. The patient was alive with stable disease at 3-month follow-up after initiation of palliative chemotherapy.
CONCLUSION
Despite timely multimodality therapy, MU may present with a hostile clinical course with a short disease-free interval and early recurrence.
Topics: Humans; Male; Brachytherapy; Burns; Combined Modality Therapy; Neck Dissection; Neoplasm Recurrence, Local; Parotid Neoplasms; Plastic Surgery Procedures; Scalp; Skin Neoplasms; Skin Ulcer; Treatment Outcome; Adult
PubMed: 38861212
DOI: 10.25270/wnds/23138 -
Cell Reports. Medicine Jun 2024When applied as the standard therapeutic modality, intensity-modulated radiotherapy (IMRT) improves local control and survival rates in patients with nasopharyngeal... (Review)
Review
When applied as the standard therapeutic modality, intensity-modulated radiotherapy (IMRT) improves local control and survival rates in patients with nasopharyngeal carcinoma (NPC). However, distant metastasis continues to be the leading cause of treatment failure. Here, we review the most recent optimization strategies for combining chemotherapy with IMRT in high-risk patients with locoregionally advanced NPC. We focus on major clinical trials on induction chemotherapy and metronomic adjuvant chemotherapy, emphasizing their efficacy in mitigating distant metastasis and prognosis. We also highlight innovations in reducing toxicity in low-risk patients, particularly through approaches of excluding chemotherapy, adopting equivalent low-toxicity drugs, or selectively exempting lymph nodes with low metastatic risk from irradiation. These approaches have provided positive treatment outcomes and significantly enhanced patients' quality of life. Finally, we provide an overview of the evolving immunotherapy landscape, with a focus on the ongoing trials and future potential of immune checkpoint inhibitors in advanced NPC treatment.
Topics: Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Immunotherapy; Radiotherapy, Intensity-Modulated; Treatment Outcome; Immune Checkpoint Inhibitors; Clinical Trials as Topic; Quality of Life
PubMed: 38843843
DOI: 10.1016/j.xcrm.2024.101594 -
Frontiers in Cell and Developmental... 2024Metronomic chemotherapy (MCT), characterized by the continuous administration of chemotherapeutics at a lower dose without prolonged drug-free periods, has garnered... (Review)
Review
Metronomic chemotherapy (MCT), characterized by the continuous administration of chemotherapeutics at a lower dose without prolonged drug-free periods, has garnered significant attention over the last 2 decades. Extensive evidence from both pre-clinical and clinical settings indicates that MCT induces distinct biological effects than the standard Maximum Tolerated Dose (MTD) chemotherapy. The low toxicity profile, reduced likelihood of inducing acquired therapeutic resistance, and low cost of MCT render it an attractive chemotherapeutic regimen option. One of the most prominent aspects of MCT is its anti-angiogenesis effects. It has been shown to stimulate the expression of anti-angiogenic molecules, thereby inhibiting angiogenesis. In addition, MCT has been shown to decrease the regulatory T-cell population and promote anti-tumor immune response through inducing dendritic cell maturation and increasing the number of cytotoxic T-cells. Combination therapies utilizing MCT along with oncolytic virotherapy, radiotherapy or other chemotherapeutic regimens have been studied extensively. This review provides an overview of the current status of MCT research and the established mechanisms of action of MCT treatment and also offers insights into potential avenues of development for MCT in the future.
PubMed: 38813084
DOI: 10.3389/fcell.2024.1369597 -
European Journal of Obstetrics &... Jun 2024Recurrence rates of FIGO stage IB-IIA and IIB-IVA cervical cancer 28-64 respectively. There is a scarcity of data on the recurrence recurrence pattern for unusual...
To study the survival outcomes of uncommon recurrences among patients with cervical cancer compared with loco-regional and nodal recurrences at a tertiary care center in North East India - Bridging the knowledge gap in the existing literature.
BACKGROUND
Recurrence rates of FIGO stage IB-IIA and IIB-IVA cervical cancer 28-64 respectively. There is a scarcity of data on the recurrence recurrence pattern for unusual sites and theirrecurrence pattern for unusual sites and its association with survival and prognosis.
OBJECTIVE
To study overall survival in patients with distant metastasis compared to local and regional nodal metastasis.
METHODS
A retrospective study was done from 1/1/2017 to 30/12/22. Cervical cancer patients post primary treatments were included. Survival was analyzed with respect to 3 groups local, regional nodalconducted from 1/1/2017 to 30/12/22. Cervical cancer patients who had received primary post-primary treatments were included. Survival was analyzed with respect to three groups: local, regional nodal, and distant metastasis.
RESULTS
225 patients had recurrences post-completion of primary treatment, of which 105 (46.6%)(46.6 %) had local, 46 (20.4%)(20.4 %) had regional nodal, and 74 (33.3 %) had distant recurrences. The median time for recurrence in local, regional nodal, and atypical recurrences were 9, 9, and 13 months (p value - <0.05), respectively. Treatment included systemic chemotherapy 122 (54.2 %), metronomic therapy 19 (8.4 %), palliative radiotherapy 44 (19.5 %), palliative surgery 8 (3.5 %) and best supportive care 30 (13.3 %) patients. Median Time to treatment-death of patients after recurrence in local, nodal and distant recurrences was 17.0 months, 18.0 months and 10.0 months respectively (p value - < 0.05). Overall Survival of patients after primary treatment with local, nodal and distant recurrences was 35.0 months, 47.0 months and 50.0 months respectively (p value <0.05).
CONCLUSION
Local recurrence is most common, followed by regional, nodal, and distant recurrences. Overall survival post recurrence was lowest for distant recurrences and highest for local recurrences however overall survival after primary treatment completion was highest for distant recurrence due to the late presen; however, tation of distant recurrences.
PubMed: 38770162
DOI: 10.1016/j.eurox.2024.100314 -
Exploration of Targeted Anti-tumor... 2024Triple negative breast cancer (TNBC) is usually treated with high doses of paclitaxel, whose effectiveness may be modulated by the action of environmental contaminants...
AIM
Triple negative breast cancer (TNBC) is usually treated with high doses of paclitaxel, whose effectiveness may be modulated by the action of environmental contaminants such as hexachlorobenzene. High doses of paclitaxel cause adverse effects such as low cellular selectivity and the generation of resistance to treatment due to an increase in the expression of multidrug resistance proteins (MRPs). These effects can be reduced using a metronomic administration scheme with low doses. This study aimed to investigate whether hexachlorobenzene modulates the response of cells to conventional chemotherapy with paclitaxel or metronomic chemotherapy with paclitaxel plus carbachol, as well as to study the participation of the MRP ATP-binding cassette transporter G2 (ABCG2) in human TNBC MDA-MB231 cells.
METHODS
Cells were treated with hexachlorobenzene alone or in combination with conventional or metronomic chemotherapies. The effects of treatments on cell viability were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the nuclear factor kappa B pathway participation was evaluated using a selective inhibitor. ABCG2 expression and its modulation were determined by western blot.
RESULTS
Results confirmed that paclitaxel reduces MDA-MB231 cell viability in a concentration-dependent manner. Results also showed that both conventional and metronomic chemotherapies reduced cell viability with similar efficacy. Although hexachlorobenzene did not modify cell viability , it did reverse the effect induced by the conventional chemotherapy, without affecting the efficacy of the metronomic chemotherapy. Additionally, a differential modulation of ABCG2 expression was determined, mediated by the nuclear factor kappa B pathway, which was directly related to the modulation of cell sensitivity to another cycle of paclitaxel treatment.
CONCLUSIONS
The findings indicate that, in human TNBC MDA-MB231 cells, in the presence of hexachlorobenzene, the metronomic combination of paclitaxel plus carbachol is more effective in affecting the tumor biology than the conventional therapeutic administration scheme of paclitaxel.
PubMed: 38745771
DOI: 10.37349/etat.2024.00218 -
BMC Immunology May 2024Metronomic capecitabine used as an adjuvant therapy improves survival in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This therapeutic...
INTRODUCTION
Metronomic capecitabine used as an adjuvant therapy improves survival in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This therapeutic approach may also contribute to improving immune function, consequently enhancing overall therapeutic efficacy.
AIM
We aimed to evaluate the effect of metronomic capecitabine as adjuvant therapy on immune function and survival in cases of LA-NPC.
SUBJECTS AND METHODS
28 patients with LA-NPC were enrolled in the study and equally assigned to two groups of 14 each: experimental and control group. The experimental group received induction chemotherapy + concurrent chemotherapy + adjuvant chemotherapy as well as oral capecitabine at a dose of 650 mg/m² of body surface area twice daily for 1 year, with the option to discontinue in case of intolerance. The control group did not receive additional chemotherapy or targeted drugs after the induction chemotherapy + concurrent chemoradiotherapy; however, they were followed up regularly. Changes in immune function and survival were compared between the two groups.
RESULTS
The median follow-up time was 43.5 months. One year after adjuvant chemotherapy, the experimental group showed higher levels of CD8 + cells, CD28 + CD8 + cells, and activated CD8 + cells compared to the control group (P < 0.05). The CD4/CD8 ratio and proportion of monocyte-derived dendritic cells were also higher in the experimental group than in the control group, but the difference was not statistically significant (P ≥ 0.05). Comparisons of 3-year overall survival, local-regional recurrence-free survival, progression-free survival, and distant metastasis-free survival between the two groups showed percentages of 92.9% vs. 78.6%, 92.9% vs. 92.9%, 78.6% vs. 71.4%, and 85.7% vs. 0.78 0.6% respectively, but these differences were not significant (P > 0 0.05 ).
CONCLUSION
Metronomic capecitabine chemotherapy was observed to induce an immunomodulatory effect in LA-NPC.
TRIAL REGISTRATION
NCT02958111, date of registration 04-11-2016.
Topics: Humans; Capecitabine; Male; Nasopharyngeal Carcinoma; Female; Middle Aged; Administration, Metronomic; Adult; Chemotherapy, Adjuvant; Nasopharyngeal Neoplasms; CD8-Positive T-Lymphocytes; Aged; Neoplasm Staging; Treatment Outcome; Antimetabolites, Antineoplastic; Follow-Up Studies
PubMed: 38710996
DOI: 10.1186/s12865-024-00621-3 -
Cancer Letters Jun 2024Metronomic chemotherapy (mCHEMO), based on frequent, regular administration of low, but pharmacologically active drug doses, optimizes antitumor efficacy by targeting... (Review)
Review
Metronomic chemotherapy (mCHEMO), based on frequent, regular administration of low, but pharmacologically active drug doses, optimizes antitumor efficacy by targeting multiple targets and reducing toxicity of antineoplastic drugs. This minireview will summarize preclinical and clinical studies on cytotoxic drugs given at weekly, daily, or at continuous metronomic schedules alone or in combination with novel targeted agents for hematological malignancies, including lymphoma, multiple myeloma, and leukemia. Most of the preclinical in vitro and in vivo studies have reported a significant benefit of both mCHEMO monotherapy and combinatorial regimens compared with chemotherapy at the maximum tolerated dose. However, the combination of mCHEMO with targeted drugs is still little explored in the hematologic clinical setting. Data obtained from preclinical studies on low dose metronomic chemotherapy in hematological malignancies clearly suggested the possibility to clinically investigate more tolerable and effective strategies for the treatment of patients with advanced hematological malignancies, or at least for those frail and elderly patients, who are not eligible or resistant to standard treatments.
Topics: Humans; Administration, Metronomic; Hematologic Neoplasms; Antineoplastic Agents; Animals; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38636896
DOI: 10.1016/j.canlet.2024.216900 -
Breast Cancer (Dove Medical Press) 2024Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only... (Clinical Trial)
Clinical Trial
Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.
PURPOSE
Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not.
PATIENTS AND METHODS
We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes.
RESULTS
All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06).
CONCLUSION
This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.
PubMed: 38628818
DOI: 10.2147/BCTT.S447290 -
Breast (Edinburgh, Scotland) Jun 2024Optimizing chemotherapy to achieve disease and symptoms control is a noteworthy purpose in advanced breast cancer (ABC). We reported the activity and quality of life of... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Phase II randomized trial comparing metronomic anthracycline-containing chemotherapy versus standard schedule in untreated HER2 negative advanced breast cancer: activity and quality of life results of the GOIM 21003 trial.
BACKGROUND
Optimizing chemotherapy to achieve disease and symptoms control is a noteworthy purpose in advanced breast cancer (ABC). We reported the activity and quality of life of a phase II study, comparing metronomic regimen with standard schedule as first line chemotherapy for ABC.
METHODS
Patients with HER2 negative ABC were randomized to non-pegylated liposomal doxorubicin (NPLD, 60 mg/m2 every 3 weeks) and cyclophosphamide (CTX, 600 mg/m2 every 3 weeks) (Arm A) or NPLD (20 mg/m2 day, on day 1, 8 and 15 every 4 weeks) and metronomic daily oral CTX 50 mg (ARM B). Primary end-points were overall response rate (ORR) and quality of life, secondary progression-free survival (PFS), overall survival (OS) and toxicity.
RESULTS
From August 2012 to December 2017, 121 patients were enrolled, 105 evaluable. Median follow-up was 21.3 months. Most patients had hormone receptor positive. ORR was 43 % in arm A and 50 % in arm B. Median PFS was 8.9 months in arm A and 6,4 months in arm B. There was no difference in OS. Total score was not clinically different between the two arms. Grade 4 neutropenia was observed in 12 patients and 16 patients respectively; alopecia G2 in 41 % (77 %) vs 14 (27 %) in arm A and in arm B respectively. One cardiac toxicity was observed (arm A).
CONCLUSIONS
First line metronomic chemotherapy for HER2 negative ABC had similar clinical activity and quite better tolerability than standard schedule and could be considered a further treatment option when chemotherapy is indicated.
Topics: Humans; Female; Breast Neoplasms; Middle Aged; Quality of Life; Administration, Metronomic; Cyclophosphamide; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Receptor, ErbB-2; Progression-Free Survival; Drug Administration Schedule; Treatment Outcome; Anthracyclines; Polyethylene Glycols
PubMed: 38615483
DOI: 10.1016/j.breast.2024.103725