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Cancer Medicine Nov 2019Consensus is lacking regarding the optimal salvage therapy for patients with follicular lymphoma who relapse after or are refractory to immunochemotherapy.
Response-adapted treatment with rituximab, bendamustine, mitoxantrone, and dexamethasone followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma after first-line immunochemotherapy: Results of the RBMDGELTAMO08 phase II trial.
BACKGROUND
Consensus is lacking regarding the optimal salvage therapy for patients with follicular lymphoma who relapse after or are refractory to immunochemotherapy.
METHODS
This phase II trial evaluated the efficacy and safety of response-adapted therapy with rituximab, bendamustine, mitoxantrone, and dexamethasone (RBMD) in follicular lymphoma patients who relapsed after or were refractory to first-line immunochemotherapy. Sixty patients received three treatment cycles, and depending on their response received an additional one (complete/unconfirmed complete response) or three (partial response) cycles. Patients who responded to induction received rituximab maintenance therapy for 2 years.
RESULTS
Thirty-three (55%) and 42 (70%) patients achieved complete/unconfirmed complete response after three cycles and on completing induction therapy (4-6 cycles), respectively (final overall response rate, 88.3%). Median progression-free survival was 56.4 months (median follow-up, 28.3 months; 95% CI, 15.6-51.2). Overall survival was not reached. Progression-free survival did not differ between patients who received four vs six cycles (P = .6665), nor between patients who did/did not receive rituximab maintenance after first-line therapy (P = .5790). Median progression-free survival in the 10 refractory patients was 25.5 months (95% CI, 0.6-N/A) and was longer in patients who had shown progression of disease after 24 months of first-line therapy (median, 56.4 months; 95% CI, 19.8-56.4) than in those who showed early progression (median, 42.31 months; 95% CI, 24.41-NA) (P = .4258). Thirty-six (60%) patients had grade 3/4 neutropenia. Grade 3/4 febrile neutropenia and infection were recorded during induction (4/60 [6.7%] and 5/60 [8.3%] patients, respectively) and maintenance (2/43 [4.5%] and 4/43 [9.1%] patients, respectively).
CONCLUSIONS
This response-adapted treatment with RBMD followed by rituximab maintenance is an effective and well-tolerated salvage treatment for relapsed/refractory follicular lymphoma following first-line immunochemotherapy.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov # NCT01133158.
Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Dexamethasone; Drug Resistance, Neoplasm; Female; Humans; Immunotherapy; Lymphoma, Follicular; Male; Middle Aged; Mitoxantrone; Neoplasm Recurrence, Local; Progression-Free Survival; Rituximab; Salvage Therapy
PubMed: 31573746
DOI: 10.1002/cam4.2555 -
Taiwanese Journal of Obstetrics &... Sep 2019
Topics: Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Gestational Trophoblastic Disease; Humans; Mitoxantrone; Prednimustine; Pregnancy
PubMed: 31542075
DOI: 10.1016/j.tjog.2019.07.001 -
International Journal of Molecular... Jun 2022The medical application of cannabidiol (CBD) has been gathering increasing attention in recent years. This non-psychotropic cannabis-derived compound possesses...
The medical application of cannabidiol (CBD) has been gathering increasing attention in recent years. This non-psychotropic cannabis-derived compound possesses antiepileptic, antipsychotic, anti-inflammatory and anxiolytic properties. Recent studies report that it also exerts antineoplastic effects in multiple types of cancers, including melanoma. In this in vitro study we tried to reveal the anticancer properties of CBD in malignant melanoma cell lines (SK-MEL 28, A375, FM55P and FM55M2) administered alone, as well as in combination with mitoxantrone (MTX) or cisplatin (CDDP). The effects of CBD on the viability of melanoma cells were measured by the MTT assay; cytotoxicity was determined in the LDH test and proliferation in the BrdU test. Moreover, the safety of CBD was tested in human keratinocytes (HaCaT) in LDH and MTT tests. Results indicate that CBD reduces the viability and proliferation of melanoma-malignant cells and exerts additive interactions with MTX. Unfortunately, CBD produced antagonistic interaction when combined with CDDP. CBD does not cause significant cytotoxicity in HaCaT cell line. In conclusion, CBD may be considered as a part of melanoma multi-drug therapy when combined with MTX. A special attention should be paid to the combination of CBD with CDDP due to the antagonistic interaction observed in the studied malignant melanoma cell lines.
Topics: Cannabidiol; Cell Line; Cisplatin; Humans; Melanoma; Mitoxantrone
PubMed: 35743195
DOI: 10.3390/ijms23126752 -
Haematologica Apr 2019
Phase I/II trial of cladribine, high-dose cytarabine, mitoxantrone, and G-CSF with dose-escalated mitoxantrone for relapsed/refractory acute myeloid leukemia and other high-grade myeloid neoplasms.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cladribine; Disease-Free Survival; Female; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mitoxantrone; Survival Rate
PubMed: 30409798
DOI: 10.3324/haematol.2018.204792 -
Journal of Cancer Research and Clinical... Sep 2022Curative intended treatment is challenging in patients with relapsed or refractory acute myeloid leukemia (r/r AML) and associated with a dismal prognosis for long-term...
PURPOSE
Curative intended treatment is challenging in patients with relapsed or refractory acute myeloid leukemia (r/r AML) and associated with a dismal prognosis for long-term survival. Despite novel treatment options, the majority of patients are treated with chemotherapy-based regimens. Although widely used, little data exist on the combination of fludarabine, cytarabine, granulocyte colony stimulating factor (FLAG) and mitoxantrone as salvage strategy for r/r AML.
MATERIALS AND METHODS
Sixty-six patients receiving Mito-FLAG for r/r AML treated at a German tertiary care center between 2009 and 2019 were analyzed with regard to response rates, survival and safety profile.
RESULTS
Overall response rate was 75.8% with 56.1% of patients achieving complete remission (CR) and 19.7% partial remission (PR). After a median follow-up of 54 months, median overall survival (OS) was 13 months. Patients transitioned to allogeneic hematopoietic stem cell transplantation (alloHSCT) (75.8%) showed a significant improvement in OS with a median OS of 17 (95% CI 8.5-25.4) months vs 3 (95% CI 1.7-4.3) months (p < 0.001). 30- and 60-day mortality rates for all patients after the initial cycle of Mito-FLAG were 4.5% and 7.6%, respectively.
CONCLUSION
The Mito-FLAG salvage protocol represents an effective and feasible treatment regimen for r/r AML. Importantly, a high rate of transition to successful alloHSCT with the aim of long-term disease-free survival has been shown.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Mitoxantrone; Prognosis; Remission Induction; Salvage Therapy; Treatment Outcome; Vidarabine
PubMed: 34609595
DOI: 10.1007/s00432-021-03821-1 -
Biochimica Et Biophysica Acta.... May 2020Molecular interactions of tumor cells with the microenvironment are regarded as onset of chemotherapy resistance, referred to as cell adhesion mediated drug resistance...
Molecular interactions of tumor cells with the microenvironment are regarded as onset of chemotherapy resistance, referred to as cell adhesion mediated drug resistance (CAM-DR). Here we elucidate a mechanism of CAM-DR in breast cancer cells in vitro. We show that human MCF-7 and MDA-MB-231 breast cancer cells decrease their sensitivity towards cisplatin, doxorubicin, and mitoxantrone cytotoxicity upon binding to collagen type 1 (COL1) or fibronectin (FN). The intracellular concentrations of doxorubicin and mitoxantrone were decreased upon cell cultivation on COL1, while cellular cisplatin levels remained unaffected. Since doxorubicin and mitoxantrone are transporter substrates, this refers to ATP binding cassette (ABC) efflux transporter activities. The activation of the transporters BCRP, P-gp and MRP1 was shown by fluorescence assays to distinguish the individual input of these transporters to resistance in presence of COL1 and related to their expression levels by western blot. An ABC transporter inhibitor was able to re-sensitize COL1-treated cells for doxorubicin and mitoxantrone toxicity. Antibody-blocking of β-integrin (ITGB1) induced sensitization towards the indicated cytostatic drugs by attenuating the increased ABC efflux activity. This refers to a key role of ITGB1 for matrix binding and subsequent transporter activation. A downregulation of αβ integrin following COL1 binding appears as clear indication for the relationship between ITGB1 and ABC transporters in regulating resistance formation, while knockdown of ITGB1 leads to a significant upregulation of all three transporters. Our data provide evidence for a role of CAM-DR in breast cancer via an ITGB1 - transporter axis and offer promising therapeutic targets for cancer sensitization.
Topics: Antineoplastic Agents; Breast Neoplasms; Cell Adhesion; Cell Line, Tumor; Cisplatin; Collagen Type I; Doxorubicin; Drug Resistance, Neoplasm; Extracellular Matrix; Female; Fibronectins; Humans; Integrin beta1; MCF-7 Cells; Mitoxantrone
PubMed: 31987794
DOI: 10.1016/j.bbamcr.2020.118663 -
Cancer May 2012Although the long natural history of prostate cancer presents challenges in the development of novel therapeutics, major contributions have been observed recently. A... (Review)
Review
Although the long natural history of prostate cancer presents challenges in the development of novel therapeutics, major contributions have been observed recently. A better understanding of the long-term complications of androgen deprivation has changed the initial approach to most patients with advanced disease. Specifically, recognition of the limitations of prostate-specific antigen has driven the pursuit of new tools capable of becoming true surrogates for disease outcome. Understanding the molecular biology of castration-resistant prostate cancer (CRPC) has led to a dramatic paradigm shift in the treatment of patients with metastatic disease where the androgen receptor becomes a central therapeutic target. Specific adrenal inhibitors and engineered super androgen receptor inhibitors have become the most promising agents in the disease. Novel immune therapies have been shown to improve survival in selected patients with castration-resistant disease despite the inability to impact traditional markers of response. Similarly, agents such as cabazitaxel and abiraterone acetate have demonstrated clinical benefit are now a standard of care in docetaxel-refractory metastatic CRPC patients. All these changes have occurred in a relatively short period and are likely to change the prostate cancer treatment paradigm. This review summarizes the current management of CRPC and discusses potential future directions.
Topics: Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Humans; Immunotherapy; Male; Mitoxantrone; Orchiectomy; Prostatic Neoplasms; Receptors, Androgen; Taxoids
PubMed: 22038761
DOI: 10.1002/cncr.26582 -
Biomolecules May 2023Doxorubicin (DOX) and mitoxantrone (MTX) are classical chemotherapeutic agents used in cancer that induce similar clinical cardiotoxic effects, although it is not clear...
Doxorubicin (DOX) and mitoxantrone (MTX) are classical chemotherapeutic agents used in cancer that induce similar clinical cardiotoxic effects, although it is not clear if they share similar underlying molecular mechanisms. We aimed to assess the effects of DOX and MTX on the cardiac remodeling, focusing mainly on metabolism and autophagy. Adult male CD-1 mice received pharmacologically relevant cumulative doses of DOX (18 mg/kg) and MTX (6 mg/kg). Both DOX and MTX disturbed cardiac metabolism, decreasing glycolysis, and increasing the dependency on fatty acids (FA) oxidation, namely, through decreased AMP-activated protein kinase (AMPK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) content and decreased free carnitine (C0) and increased acetylcarnitine (C2) concentration. Additionally, DOX heavily influenced glycolysis, oxidative metabolism, and amino acids turnover by exclusively decreasing phosphofructokinase (PFKM) and electron transfer flavoprotein-ubiquinone oxidoreductase (ETFDH) content, and the concentration of several amino acids. Conversely, both drugs downregulated autophagy given by the decreased content of autophagy protein 5 (ATG5) and microtubule-associated protein light chain 3 (LC3B), with MTX having also an impact on Beclin1. These results emphasize that DOX and MTX modulate cardiac remodeling differently, despite their clinical similarities, which is of paramount importance for future treatments.
Topics: Male; Mice; Animals; Mitoxantrone; Ventricular Remodeling; Antineoplastic Agents; Doxorubicin; Autophagy; Amino Acids; Myocytes, Cardiac; Apoptosis; Oxidative Stress
PubMed: 37371499
DOI: 10.3390/biom13060921 -
Biomaterials Advances Aug 2023Photothermal therapy has emerged as a new promising strategy for the management of cancer, either alone or combined with other therapeutics, such as chemotherapy. The...
Photothermal therapy has emerged as a new promising strategy for the management of cancer, either alone or combined with other therapeutics, such as chemotherapy. The use of nanoparticles for multimodal therapy can improve treatment performance and reduce drug doses and associated side effects. Here we propose the development of a novel multifunctional nanosystem based on solid lipid nanoparticles co-loaded with gold nanorods and mitoxantrone and functionalized with folic acid for dual photothermal therapy and chemotherapy of breast cancer. Nanoparticles were produced using an economically affordable method and presented suitable physicochemical properties for tumor passive accumulation. Upon Near-Infrared irradiation (808 nm, 1.7 W cm, 5 min), nanoparticles could effectively mediate a temperature increase of >20 °C. Moreover, exposure to light resulted in an enhanced release of Mitoxantrone. Furthermore, nanoparticles were non-hemolytic and well tolerated by healthy cells even at high concentrations. The active targeting strategy was found to be successful, as shown by the greater accumulation of the functionalized nanoparticles in MCF-7 cells. Finally, the combined effects of chemotherapy, light-induced drug release and photothermal therapy significantly enhanced breast cancer cell death. Overall, these results demonstrate that the developed lipid nanosystem is an efficient vehicle for breast cancer multimodal therapy.
Topics: Humans; Female; Breast Neoplasms; Mitoxantrone; Photothermal Therapy; Nanoparticles
PubMed: 37146526
DOI: 10.1016/j.bioadv.2023.213443 -
Journal of the American Veterinary... Dec 2012A 5-year-old sexually intact male Giant Schnauzer was evaluated because of difficulty breathing and left pelvic limb swelling. Eighteen months previously, the patient...
CASE DESCRIPTION
A 5-year-old sexually intact male Giant Schnauzer was evaluated because of difficulty breathing and left pelvic limb swelling. Eighteen months previously, the patient had had intermittent left pelvic limb swelling, but the owner declined further testing at that time.
CLINICAL FINDINGS
Physical examination revealed severe pitting edema of the left pelvic limb and prepuce and muffled heart sounds on thoracic auscultation. Results of thoracic radiography and thoracocentesis were consistent with chylothorax, and CT imaging of the thorax and abdomen revealed a mass involving the whole left sublumbar area.
TREATMENT AND OUTCOME
In an attempt to treat the chylothorax, pleural omentalization and pericardectomy were performed. Histologic evaluation of several biopsy specimens harvested in the abdominal and thoracic cavities revealed disseminated lymphangiosarcoma. The patient recovered well from surgery, and mitoxantrone chemotherapy was administered. As of 10 months after surgery, the dog was clinically normal except for mild pelvic limb edema.
CLINICAL RELEVANCE
The combination of clinical signs, multiple imaging features, surgical findings, and histologic examination findings enabled the final diagnosis of lymphangiosarcoma. Clinical management that included medical and surgical treatments and chemotherapy resulted in improved quality of life and extended survival time in a dog with metastatic lymphangiosarcoma.
Topics: Animals; Antineoplastic Agents; Dog Diseases; Dogs; Lymphangiosarcoma; Male; Mitoxantrone
PubMed: 23216040
DOI: 10.2460/javma.241.12.1639