-
Medicine Aug 2023Novel-fosfamides (NFOs) belong to active metabolites of ifosfamide that bypass the generation of toxic byproducts. In this analysis, we aimed to comprehensively assess... (Meta-Analysis)
Meta-Analysis
Novel-fosfamide monotherapy or in combination with doxorubicin versus doxorubicin alone in patients with advanced soft tissue sarcoma: A pooled analysis of randomized clinical trials.
BACKGROUND
Novel-fosfamides (NFOs) belong to active metabolites of ifosfamide that bypass the generation of toxic byproducts. In this analysis, we aimed to comprehensively assess the benefits and risks of NFO monotherapy or in combination with doxorubicin (DOX) versus single-drug DOX in previously untreated patients with advanced soft-tissue sarcoma (ASTS).
METHODS
Online PubMed, Web of Science, Embase, and Cochrane CENTRAL databases were systematically searched on April 26, 2022. Objective response rate and disease control rate were primary outcomes. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events were secondary outcomes.
RESULTS
In all, 3 randomized clinical trials with a total of 1207 ASTS patients were eligible. DOX plus NFO combination therapy showed higher risk ratios of objective response rate (1.50, 95% CI 1.20-1.68, P = .0003) and disease control rate (1.15, 95% CI 1.05-1.27, P = .0030) compared with DOX monotherapy. Nevertheless, NFO-based monotherapy and combination therapy were found no improvements on OS (hazard ratio 0.93, 95% CI 0.52-1.65, P = .8050) and PFS (hazard ratio 0.88, 95% CI 0.54-1.43, P = .6088) against DOX. More incidences of grade 3 or worse anemia, thrombocytopenia, stomatitis, diarrhea, constipation, and febrile neutropenia were observed in NFO-based treatments.
CONCLUSION
Adding NFO to DOX as first-line therapy improved the responses in ASTS patients but did not prolong OS and PFS. Grade 3 or worse treatment-related adverse events should be treated with caution during the NFO-based therapies.
Topics: Humans; Randomized Controlled Trials as Topic; Doxorubicin; Soft Tissue Neoplasms; Sarcoma; Thrombocytopenia
PubMed: 37603507
DOI: 10.1097/MD.0000000000034902 -
Medicine Apr 2021Uterine leiomyosarcomas are rare malignant mesenchymal tumors. The systemic treatment of these tumors includes chemotherapy and radiotherapy. However, there are still a...
BACKGROUND
Uterine leiomyosarcomas are rare malignant mesenchymal tumors. The systemic treatment of these tumors includes chemotherapy and radiotherapy. However, there are still a lot of unanswered questions regarding the ideal therapeutic approach.
METHODS
We have conducted a systematic review of the treatment strategies of uterine leiomyosarcomas for the last ten years.
RESULTS
Adjuvant chemotherapy is still a matter of dilemma. Doxorubicin based chemotherapy or the combination of Gemcitabine-Docetaxel are the regimens of choice for the first line setting. Beyond the first line, there are several options;, including chemotherapy, targeted therapy, and recently efforts of introducing immunotherapy to the therapeutic armamentarium of clinicians treating uterine leiomyosarcomas.
CONCLUSIONS
Despite the efforts of the clinicians dealing with uterine leiomyosarcomas, the optimal therapeutic algorithm is yet to be described.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Deoxycytidine; Doxorubicin; Female; Humans; Immunotherapy; Leiomyosarcoma; Molecular Targeted Therapy; Treatment Outcome; Uterine Neoplasms; Gemcitabine
PubMed: 33787622
DOI: 10.1097/MD.0000000000025309 -
Journal of Oncology Pharmacy Practice :... Mar 2021Doxorubicin- and epirubicin-induced cardiotoxicities are life threatening for those suffering from breast cancer. Comparing the effects of different strategies on the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Doxorubicin- and epirubicin-induced cardiotoxicities are life threatening for those suffering from breast cancer. Comparing the effects of different strategies on the prevention of these agent-induced cardiotoxicities remains unexplored. A comprehensive review of clinical trials was performed on the prevention of epirubicin- and/or doxorubicin-induced cardiotoxicity in HER2-positive metastatic breast cancer patients. The reduction in ejection fraction was directed at evaluating cardiac toxicity. Fourteen articles evaluated cardiotoxicity as a condition among 2945 individuals, evaluating doxorubicin, epirubicin, Liposomal Doxorubicin (LD), Pegylated Liposomal Doxorubicin (PLD), dexrazoxane plus doxorubicin or epirubicin, and Angiotensin-Converting Enzyme Inhibitors (ACEIs) plus doxorubicin. Pooled Odds Ratio (OR) of 0.043 with a 95% credible interval (CrI) between 0.005 and 0.22 indicated that the dexrazoxane plus epirubicin reduced the number of cardiac events compared with doxorubicin. Furthermore, doxorubicin and epirubicin represented the most effective interventions with a 52% probability of success. Also, the best treatment for reducing Congestive Heart Failure (CHF) was dexrazoxane plus epirubicin with a probability of 43%. For the Left Ventricular Ejection Fraction (LVEF) reduction outcome, ACEIs plus doxorubicin was ranked first with a success probability of 61.2% and they could significantly prevent the reduction in LVEF compared with LD, epirubicin, or doxorubicin.
CONCLUSION
Our data suggested that angiotensin-converting enzyme inhibitors and dexrazoxane plus epirubicin were the most effective interventions for preventing cardiotoxicity and CHF. However, ACEIs plus doxorubicin was the best treatment for preventing LVEF reduction.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiotoxicity; Dexrazoxane; Doxorubicin; Epirubicin; Female; Heart Failure; Humans; Network Meta-Analysis; Polyethylene Glycols; Randomized Controlled Trials as Topic; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left
PubMed: 33081570
DOI: 10.1177/1078155220965674 -
Cancer Radiotherapie : Journal de La... Dec 2020Alveolar rhabdomyosarcoma (ARMS) represents the most common childhood soft tissue sarcoma, but they are rarely seen among adults. Most of the protocols for adults are...
Alveolar rhabdomyosarcoma (ARMS) represents the most common childhood soft tissue sarcoma, but they are rarely seen among adults. Most of the protocols for adults are adapted from pediatric protocols. Here we report a case of a 53-year-old woman diagnosed with a nasal alveolar rhabdomyosarcoma, stage IV at diagnosis, treated by chemotherapy (a regimen inspired from the pediatric protocole pEpSSG RMS 2005) which led to partial response followed by chemo-radiotherapy. We performed a systematic review of adult head and neck ARMS and found 29 cases. Primary chemotherapy with different protocols (VAC, VAI or VIE) should be done followed by surgery and/or external beam radiotherapy (preferably with IMRT). EBRT seems beneficial to every ARMS with a dose around 50Gy in a conventional fractionation, eventually completed with a boost on residual tumor. The target volume must be defined on pre-chemotherapy imaging. Brachytherapy and proton therapy are under evaluation.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Combined Modality Therapy; Dactinomycin; Doxorubicin; Female; Humans; Ifosfamide; Middle Aged; Nose Neoplasms; Radiotherapy, Intensity-Modulated; Rhabdomyosarcoma, Alveolar; Vincristine
PubMed: 33172776
DOI: 10.1016/j.canrad.2020.03.015 -
Oncogene Jan 2023Over the last 40 years osteosarcoma (OS) survival has stagnated with patients commonly resistant to neoadjuvant MAP chemotherapy involving high dose methotrexate,...
Over the last 40 years osteosarcoma (OS) survival has stagnated with patients commonly resistant to neoadjuvant MAP chemotherapy involving high dose methotrexate, adriamycin (doxorubicin) and platinum (cisplatin). Due to the rarity of OS, the generation of relevant cell models as tools for drug discovery is paramount to tackling this issue. Four literature databases were systematically searched using pre-determined search terms to identify MAP resistant OS cell lines and patients. Drug exposure strategies used to develop cell models of resistance and the impact of these on the differential expression of resistance associated genes, proteins and non-coding RNAs are reported. A comparison to clinical studies in relation to chemotherapy response, relapse and metastasis was then made. The search retrieved 1891 papers of which 52 were relevant. Commonly, cell lines were derived from Caucasian patients with epithelial or fibroblastic subtypes. The strategy for model development varied with most opting for continuous over pulsed chemotherapy exposure. A diverse resistance level was observed between models (2.2-338 fold) with 63% of models exceeding clinically reported resistance levels which may affect the expression of chemoresistance factors. In vitro p-glycoprotein overexpression is a key resistance mechanism; however, from the available literature to date this does not translate to innate resistance in patients. The selection of models with a lower fold resistance may better reflect the clinical situation. A comparison of standardised strategies in models and variants should be performed to determine their impact on resistance markers. Clinical studies are required to determine the impact of resistance markers identified in vitro in poor responders to MAP treatment, specifically with respect to innate and acquired resistance. A shift from seeking disputed and undruggable mechanisms to clinically relevant resistance mechanisms may identify key resistance markers that can be targeted for patient benefit after a 40-year wait.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Clinical Relevance; Doxorubicin; Neoplasm Recurrence, Local; Osteosarcoma; Drug Resistance, Neoplasm
PubMed: 36434179
DOI: 10.1038/s41388-022-02529-x -
International Journal of Clinical... Aug 2020There is no standard chemotherapy available for unresectable or metastatic small bowel adenocarcinoma (SBA) because of its rarity. This systematic review aims to assess...
BACKGROUND
There is no standard chemotherapy available for unresectable or metastatic small bowel adenocarcinoma (SBA) because of its rarity. This systematic review aims to assess the efficacy and safety of chemotherapy for patients with unresectable or metastatic SBA.
METHODS
In accordance with the PRISMA statements, literature search was conducted using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. The included studies were prospective randomized, nonrandomized, or observational studies. Risk of bias was assessed the ROBINS-I tool.
RESULTS
Seven prospective single-arm Phase II studies were included in this review. Six of them were assessed as having a moderate risk of bias and one as having a serious risk of bias. A meta-analysis was not performed, because the studies were single-arm. Systemic chemotherapy based on fluoropyrimidine regimens achieved favorable outcomes with acceptable adverse effects as a first therapy; however, the regimens differed in each study. The object response rate was 18-50%, and the disease control rate was 29-87%. With 5-fluorouracil, adriamycin, and mitomycin-C regimen, one treatment-related death occurred. A second line of therapy including chemotherapy with nab-paclitaxel also showed favorable efficacy. The object response rate was 20%, and the disease control rate was 50%.
CONCLUSIONS
Systemic chemotherapy based on fluoropyrimidine regimens was mainly used for unresectable or metastatic SBA. While it may achieve favorable outcomes with acceptable adverse effects, further evidence is needed.
Topics: Adenocarcinoma; Albumins; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Fluorouracil; Humans; Intestinal Neoplasms; Intestine, Small; Paclitaxel; Prospective Studies; Treatment Outcome
PubMed: 32448950
DOI: 10.1007/s10147-020-01703-z -
Haematologica Jul 2020Central nervous system (CNS) relapse of diffuse large B-cell lymphoma remains uncommon but catastrophic. The benefit of standalone intrathecal prophylaxis in reducing...
Efficacy of central nervous system prophylaxis with stand-alone intrathecal chemotherapy in diffuse large B-cell lymphoma patients treated with anthracycline-based chemotherapy in the rituximab era: a systematic review.
Central nervous system (CNS) relapse of diffuse large B-cell lymphoma remains uncommon but catastrophic. The benefit of standalone intrathecal prophylaxis in reducing CNS recurrence is unclear and remains controversial. No systematic review analysing the evidence for stand-alone intrathecal prophylaxis has been performed in the era of anti-CD20 monoclonal antibody therapy. A comprehensive search (01/2002-01/2019) was systematically performed using Ovid MEDLINE, Ovid EMBASE and Cochrane. Studies were selected from a total of 804, screened based on predefined inclusion/exclusion criteria, and were critically appraised. Three post hoc analyses (RICOVER-60, RCHOP-14/21, GOYA), one prospective database and 10 retrospective series were included. 7,357 rituximab/obinutuzumab-exposed patients were analysed. The median percentage receiving intrathecal prophylaxis was 11.9%. Cumulative CNS relapse incidence ranged from 1.9% at 6.5 years to 8.4% at 5 years. Median time (of medians) to CNS relapse was 10 months. 73% developed isolated CNS relapses, 24% concurrent CNS/systemic relapse, and 3% post-systemic relapse. Reported CNS relapse sites were: parenchymal (58%), leptomeningeal (27%), and both (12%). Event rates were low resulting in limited power within each study to provide robust univariable/multivariable analysis. Intrathecal prophylaxis was not a univariable or multivariable factor associated with a reduction in CNS relapse in any study. We found no strong evidence for the benefit, or indeed genuine lack of benefit, of stand-alone intrathecal prophylaxis in preventing CNS relapse in diffuse large B-cell lymphoma-treated patients using anthracycline-based immunochemotherapy. Current published study designs limit the strength of such conclusions.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System; Central Nervous System Neoplasms; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Neoplasm Recurrence, Local; Prednisone; Retrospective Studies; Rituximab; Vincristine
PubMed: 31488560
DOI: 10.3324/haematol.2019.229948 -
Journal of Molecular and Cellular... Jan 2020Cardiotoxicity is a well-known adverse effect of doxorubicin (Dox) administration, but the underlying molecular mechanism of this effect is not fully understood. Over...
Cardiotoxicity is a well-known adverse effect of doxorubicin (Dox) administration, but the underlying molecular mechanism of this effect is not fully understood. Over the past two decades, considerable efforts have focused on the potential molecular targets of cardiotoxicity in the hope that novel targeted therapies will be generated to attenuate Dox-induced cardiotoxicity. Here, we provide a comprehensive overview of genetically modified animals that show enhanced or reduced susceptibility to the cardiotoxic effects of Dox. We focused on the process by which the molecules involved in DNA damage, oxidative stress, apoptosis, autophagy and necrosis are affected in the presence of Dox. We also present a protein-protein interaction network and explain the contribution of the components to the process of Dox-induced cardiotoxicity. More importantly, data from the literature have indicated that PI3Kγ and Rac1 are potential targets with therapeutic advantages in cancer therapy; molecules that target these proteins can simultaneously attenuate Dox-induced cardiotoxicity and enhance its anticancer activity. This review highlights the potential molecular targets that are critical regulators involved in Dox-mediated cardiotoxicity, thus providing further insight into the development of potential treatment strategies to prevent the cardiotoxic effects and enhance the anticancer efficiency of Dox in cancer patients.
Topics: Animals; Autophagy; Cardiotoxicity; DNA Damage; Doxorubicin; Humans; Molecular Targeted Therapy; Oxidative Stress
PubMed: 31751567
DOI: 10.1016/j.yjmcc.2019.11.150 -
International Journal of Clinical... May 2024Granulocyte colony-stimulating factor (G-CSF) decreases the incidence, duration, and severity of febrile neutropenia (FN); however, dose reduction or withdrawal is often... (Meta-Analysis)
Meta-Analysis
Effectiveness and safety of primary prophylaxis of granulocyte colony-stimulating factor during dose-dense chemotherapy for urothelial cancer: Clinical Practice Guidelines for the Use of G-CSF 2022.
Granulocyte colony-stimulating factor (G-CSF) decreases the incidence, duration, and severity of febrile neutropenia (FN); however, dose reduction or withdrawal is often preferred in the management of adverse events in the treatment of urothelial cancer. It is also important to maintain therapeutic intensity in order to control disease progression and thereby relieve symptoms, such as hematuria, infection, bleeding, and pain, as well as to prolong the survival. In this clinical question, we compared treatment with primary prophylactic administration of G-CSF to maintain therapeutic intensity with conventional standard therapy without G-CSF and examined the benefits and risks as major outcomes. A detailed literature search for relevant studies was performed using PubMed, Ichu-shi Web, and Cochrane Library. Data were extracted and evaluated independently by two reviewers. A qualitative analysis of the pooled data was performed, and the risk ratios with corresponding confidence intervals were calculated and summarized in a meta-analysis. Seven studies were included in the qualitative analysis, two of which were reviewed in the meta-analysis of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) therapy, and one randomized controlled study showed a reduction in the incidence of FN. Primary prophylactic administration of G-CSF may be beneficial, as shown in a randomized controlled study of dose-dense MVAC therapy. However, there are no studies on other regimens, and we made a "weak recommendation to perform" with an annotation of the relevant regimen (dose-dense MVAC).
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Febrile Neutropenia; Granulocyte Colony-Stimulating Factor; Methotrexate; Urologic Neoplasms; Vinblastine
PubMed: 38517658
DOI: 10.1007/s10147-024-02491-6 -
Revista Espanola de Geriatria Y... 2024The increasing aging of the population brings with it an increase in the incidence of neurocognitive disorder (NCD) as well as various situations that generate...
INTRODUCTION
The increasing aging of the population brings with it an increase in the incidence of neurocognitive disorder (NCD) as well as various situations that generate dependence.
OBJECTIVE
To analyze by means of a systematic review the relationship between NCD and dependence with the risk of mortality in the elderly.
METHODS
A bibliographic search of longitudinal studies published in Pubmed and Scopus addressing the relationship between NCI, dependence for basic activities of daily living (ADL) and mortality published between 1995 and 2021 was performed. Of the 1040 articles found, 10 studies were selected.
RESULTS
It was observed that cohorts of elderly people with NCI presented mortality risk associated with ABVD impairment (Barthel test) and Mini-Mental State Examination scores following a significant linear trend. Other factors associated with mortality risk were low levels of education, living alone, and frailty.
CONCLUSIONS
The results underline the importance of performing assessments of cognitive and functional status using validated scales, since both areas are associated with mortality. The link between the three terms used in the search for this work is clear, but it is noteworthy that there are few longitudinal studies that analyze them together. The assessment of dependence and cognitive function in older adults should be considered in both research and clinical practice as it would provide information on their possible relationship with mortality.
Topics: Humans; Aged; Activities of Daily Living; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dacarbazine; Doxorubicin; Hodgkin Disease; Vinblastine; Neurocognitive Disorders
PubMed: 37820397
DOI: 10.1016/j.regg.2023.101411