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Child's Nervous System : ChNS :... May 2024Pediatric low-grade gliomas (PLGG) are commonly treated with a combination of surgery, radiotherapy, and chemotherapy. Recent trends prioritize reducing long-term...
Pediatric low-grade gliomas (PLGG) are commonly treated with a combination of surgery, radiotherapy, and chemotherapy. Recent trends prioritize reducing long-term morbidities, particularly in younger patients. While historically chemotherapy was reserved for cases progressing after radiotherapy, evolving recommendations now advocate for its early use, particularly in younger age groups. The carboplatin and vincristine (CV) combination stands as a standard systemic therapy for PLGG, varying in dosage and administration between North America and Europe. Clinical trials have shown promising response rates, albeit with varying toxicity profiles. Vinblastine has emerged as another effective regimen with minimal toxicity. TPCV, a regimen combining thioguanine, procarbazine, lomustine, and vincristine, was compared to CV in a Children's Oncology Group trial, showing comparable outcomes, but more toxicity. Vinorelbine, temozolomide, and metronomic chemotherapy have also been explored, with varied success rates and toxicity profiles. Around 40-50% of PLGG patients require subsequent chemotherapy lines. Studies have shown varied efficacy in subsequent lines, with NF1 patients generally exhibiting better outcomes. The identification of molecular drivers like BRAF mutations has led to targeted therapies' development, showing promise in specific molecular subgroups. Trials comparing targeted therapy to conventional chemotherapy aim to delineate optimal treatment strategies based on molecular profiles. The landscape of chemotherapy in PLGG is evolving, with a growing focus on molecular subtyping and targeted therapies. Understanding the role of chemotherapy in conjunction with novel treatments is crucial for optimizing outcomes in pediatric patients with low-grade gliomas.
PubMed: 38819670
DOI: 10.1007/s00381-024-06458-w -
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 -
Cancer Letters Jul 2024Current methods of cancer therapy have demonstrated enormous potential in tumor inhibition. However, a high dosage regimen of chemotherapy results in various... (Review)
Review
Current methods of cancer therapy have demonstrated enormous potential in tumor inhibition. However, a high dosage regimen of chemotherapy results in various complications which affect the normal body cells. Tumor cells also develop resistance against the prescribed drugs in the whole treatment regimen increasing the risk of cancer relapse. Metronomic chemotherapy is a modern treatment method that involves administering drugs at low doses continuously, allowing the drug sufficient time to take its effect. This method ensures that the toxicity of the drugs is to a minimum in comparison to conventional chemotherapy. Nanoparticles have shown efficacy in delivering drugs to the tumor cells in various cancer therapies. Combining nanoparticles with metronomic chemotherapy can yield better treatment results. This combination stimulates the immune system, improving cancer cells recognition by immune cells. Evidence from clinical and pre-clinical trials supports the use of metronomic delivery for drug-loaded nanoparticles. This review focuses on the functionalization of nanoparticles for improved drug delivery and inhibition of tumor growth. It emphasizes the mechanisms of metronomic chemotherapy and its conjunction with nanotechnology. Additionally, it explores tumor progression and the current methods of chemotherapy. The challenges associated with nano-based metronomic chemotherapy are outlined, paving the way for prospects in this dynamic field.
Topics: Humans; Administration, Metronomic; Neoplasms; Nanoparticles; Antineoplastic Agents; Animals; Drug Delivery Systems; Drug Carriers
PubMed: 38801886
DOI: 10.1016/j.canlet.2024.216990 -
Pediatric Blood & Cancer Aug 2024Metronomic chemotherapy-based combinations have received interest for relapsed/refractory malignancies. Preclinical and clinical studies showed activity of metronomic...
Metronomic chemotherapy-based combinations have received interest for relapsed/refractory malignancies. Preclinical and clinical studies showed activity of metronomic etoposide and axitinib. We report our retrospective experience in six children treated with axitinib and metronomic etoposide for refractory/relapsed brain tumors as an "off-label" combination. Three patients with medulloblastoma experienced partial response; one patient with atypical teratoid rhabdoid tumor (ATRT) displays an ongoing stable disease (12 months); two patients with medulloblastoma had progressive disease. Grade 3-4 toxicities were observed in two patients (thrombocytopenia, anemia, diarrhea, fatigue). The axitinib-etoposide combination shows signals of efficacy in heavily pretreated patients with relapsed/refractory brain tumors. These results were based on real-world observation and will need formal evaluation in a phase I/II trial.
Topics: Humans; Male; Retrospective Studies; Female; Etoposide; Antineoplastic Combined Chemotherapy Protocols; Child; Axitinib; Brain Neoplasms; Child, Preschool; Neoplasm Recurrence, Local; Adolescent; Administration, Metronomic; Administration, Oral; Follow-Up Studies; Prognosis; Infant
PubMed: 38778441
DOI: 10.1002/pbc.31076 -
Small (Weinheim An Der Bergstrasse,... May 2024Immuno-stimulative effect of chemotherapy (ISECT) is recognized as a potential alternative to conventional immunotherapies, however, the clinical application is... (Review)
Review
Immuno-stimulative effect of chemotherapy (ISECT) is recognized as a potential alternative to conventional immunotherapies, however, the clinical application is constrained by its inefficiency. Metronomic chemotherapy, though designed to overcome these limitations, offers inconsistent results, with effectiveness varying based on cancer types, stages, and patient-specific factors. In parallel, a wealth of preclinical nanomaterials holds considerable promise for ISECT improvement by modulating the cancer-immunity cycle. In the area of biomedical nanomaterials, current literature reviews mainly concentrate on a specific category of nanomaterials and nanotechnological perspectives, while two essential issues are still lacking, i.e., a comprehensive analysis addressing the causes for ISECT inefficiency and a thorough summary elaborating the nanomaterials for ISECT improvement. This review thus aims to fill these gaps and catalyze further development in this field. For the first time, this review comprehensively discusses the causes of ISECT inefficiency. It then meticulously categorizes six types of nanomaterials for improving ISECT. Subsequently, practical strategies are further proposed for addressing inefficient ISECT, along with a detailed discussion on exemplary nanomedicines. Finally, this review provides insights into the challenges and perspectives for improving chemo-immunotherapy by innovations in nanomaterials.
PubMed: 38773882
DOI: 10.1002/smll.202403024 -
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 -
Journal of Chemotherapy (Florence,... May 2024First line endocrine therapy is the gold standard for advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative breast cancer. Adding CDK4/6...
First line endocrine therapy is the gold standard for advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative breast cancer. Adding CDK4/6 inhibitors has improved progression free survival. Metronomic Capecitabine has proven to be safe to combine with endocrine therapy with promising efficacy. We conducted a phase II randomized, open label, single centre clinical trial on patients with metastatic ER positive and HER 2 negative breast cancer. Eligible patients were randomized (1:1) to arm A: metronomic dose of capecitabine (500 mg/m BID) combined with letrozole (2.5 mg OD) or arm B: letrozole single agent. The primary endpoint was progression free survival. The study was terminated early due to poor accrual and 60 eligible patients out of the planned 204 were randomized. This clinical trial is registered on ClinicalTrials.gov (MD-127-2019, NCT04571437). Between February 2019 and April 2022, 60 patients were randomized. This is the first report of the study, after a median follow-up of 18.6 months. The median age at diagnosis was 47 years with only 41.7% of patients post-menopausal. Half of our patients had bone-only disease, 45% had visceral metastasis (liver and lung) and 63% presented with endocrine sensitive disease. The estimated median PFS for the whole population was 16.2 months. Median PFS for capecitabine arm was 17.7 months versus 14.6 months for letrozole alone ( = 0.078). Overall response rate was 70% for capecitabine/letrozole arm and 56.6% for letrozole only. Clinical benefit rate was 90% in the capecitabine/letrozole arm versus 73.3% in the letrozole arm. Overall survival data is still immature after this short follow up duration. Adverse event assessment showed acceptable all grade and high grade toxicity profile consistent with the established adverse events of both capecitabine and letrozole. Anaemia (28.3%) and hand & foot syndrome (43.8%) were significantly more common in the capecitabine/letrozole arm. Capecitabine combined with letrozole have showed a trend towards improvement in progression free survival with potential more benefit to certain sub-groups and the combination showed acceptable safety profile consistent with the established known safety profile of both letrozole and capecitabine.
PubMed: 38764430
DOI: 10.1080/1120009X.2024.2342741 -
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 -
Indian Journal of Surgical Oncology Jun 2024Head and neck squamous cell carcinomas (HNSCC) have proven to be inherently resistant to systemic treatments as a result of histological, molecular, and etiological...
Head and neck squamous cell carcinomas (HNSCC) have proven to be inherently resistant to systemic treatments as a result of histological, molecular, and etiological heterogeneity, with limited responses seen after second-line therapy and beyond. With limited treatment options after progression on systemic chemotherapy in HNSCCs, immunotherapy has a role to play with improved results. In this prospective, observational, non-randomized, open-label study, a total of 12 patients with advanced, relapsed, or metastatic HNSCC received Inj. Nivolumab weight-based dose of 3 mg per kg, intravenously every 2 weeks along with low-dose capecitabine 500 mg twice a day, was prospectively assessed. The patient's clinical, hematological, and staging characteristics were described and the clinical benefit rate (CBR) was calculated. A total of 12 patients received the combined metronomic chemo-immunotherapy (CMCI). The majority of patients were belonging to ECOG-PS 1(66%), with all patients being in stage IV disease. Six, four, and two patients received immunotherapy as the 5th, 3rd, and 4th line of therapy, respectively. Nivolumab and low-dose capecitabine were used in all 12 patients. CBR was seen in 66% (8/12) of patients, one patient died due to hepatitis and hepatic encephalopathy, another patient died due to pneumonia and respiratory complications, two patients had progressive disease, and two patients with stable disease discontinued treatment because of financial constraints and kept on capecitabine alone. The majority tolerated therapy well with no grade 3/4 immune-related adverse events (IRAEs). Two patients required supportive therapy with packed red cell transfusion and albumin infusions. Six-month overall survival (OS) and progression-free survival (PFS) in the study population were 83.3% and 66.6%, respectively. In conclusion, nivolumab along with metronomic chemotherapy with low-dose capecitabine was very well tolerated and exhibited anti-tumor activity with a CBR of 66%, 6-month OS of 83.3%, and 6-month PFS of 66.6%, in extensively pretreated patients with HNSCCs. Additional studies of nivolumab and metronomic chemotherapy and immuno-immuno combination therapy in these diseases are ongoing.
PubMed: 38741631
DOI: 10.1007/s13193-024-01900-6 -
JCO Global Oncology May 2024Desmoid fibromatosis (DF) is a locally aggressive tumor with low mortality but significant morbidity. There is a lack of standard of care, and existing therapies are...
PURPOSE
Desmoid fibromatosis (DF) is a locally aggressive tumor with low mortality but significant morbidity. There is a lack of standard of care, and existing therapies are associated with significant barriers including access, cost, and toxicities. This study aimed to explore the efficacy and safety of the metronomic therapy (MT) in DF in a large, homogenous cohort from India.
PATIENTS AND METHODS
This study involved histologically confirmed DF cases treated with MT comprising vinblastine (6 mg) and methotrexate (15 mg) both once a week, and tamoxifen (40 mg/m) in two divided doses once daily between 2002 and 2018.
RESULTS
There were 315 patients with a median age of 27 years; the commonest site was extremity (142 of 315; 45.0%). There were 159 (50.1%) male patients. Of the 123 (39.0%) prior treated patients, 119 had surgery. Of 315 patients, 263 (83.5%) received treatment at our institute (MT-151, 77-local treatment, 9-tyrosine kinase inhibitor, and 26 were observed). Among the MT cohort (n = 163, 61.2%), at a median follow-up of 36 (0.5-186) months, the 3-year progression-free and overall survival were 81.1% (95% CI, 74.3 to 88.4) and 99.2% (95% CI, 97.6 to 100), respectively. There were 35% partial responses. Ninety-two patients (56.4%) completed 1-year therapy, which was an independent prognosticator ( < .0001; hazard ratio, 0.177 [95% CI, 0.083 to 0.377]). MT was well tolerated. Predominant grade ≥3 toxicities were febrile neutropenia, 12 (7.4%) without any chemotoxicity-related death. The annual cost of MT was $130 US dollars.
CONCLUSION
The novel, low-cost MT qualifies as one of the effective, less toxic, sustainable, standard-of-care options for the treatment of DF with global reach and merits wide recognition.
Topics: Humans; Male; Female; Adult; Fibromatosis, Aggressive; India; Tertiary Care Centers; Young Adult; Middle Aged; Administration, Metronomic; Adolescent; Methotrexate; Standard of Care; Child; Vinblastine; Aged; Antineoplastic Combined Chemotherapy Protocols; Tamoxifen; Retrospective Studies
PubMed: 38723218
DOI: 10.1200/GO.23.00308