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Journal of Veterinary Internal Medicine 2023Visceral hemangiosarcomas (HSA) are rare in cats and typically associated with aggressive biologic behavior and poor prognosis. A 4-year-old male neutered domestic...
Visceral hemangiosarcomas (HSA) are rare in cats and typically associated with aggressive biologic behavior and poor prognosis. A 4-year-old male neutered domestic shorthair cat was presented with a 3-month history of hematuria and stranguria; ultrasonography identified a large bladder mass. Complete excision was achieved by partial cystectomy. Histopathology and immunohistochemistry for von Willebrand factor confirmed HSA. The cat was treated using adjuvant cyclophosphamide, thalidomide, and meloxicam for 8 months. Abdominal ultrasonography repeated at 2 months and computed tomography repeated at 5 and 19 months after diagnosis showed no evidence of local recurrence or metastasis. The cat was alive at last follow-up (896 days). Although the cat described in this report experienced a more favorable prognosis compared to other visceral HSA locations, additional cases are needed to further understand the biological behavior of bladder HSAs and guide treatment decisions.
Topics: Male; Cats; Animals; Urinary Bladder; Cystectomy; Hemangiosarcoma; Thalidomide; Cyclophosphamide; Adjuvants, Immunologic; Cat Diseases; Urinary Bladder Neoplasms
PubMed: 37381579
DOI: 10.1111/jvim.16750 -
Indian Journal of Surgical Oncology Jun 2023To evaluate the feasibility, tolerance, and efficacy of OMCT (oral metronomic chemotherapy) after CRS + HIPEC for peritoneal mesothelioma in patients with poor...
OBJECTIVE
To evaluate the feasibility, tolerance, and efficacy of OMCT (oral metronomic chemotherapy) after CRS + HIPEC for peritoneal mesothelioma in patients with poor prognostic factors: PCI > 20, incomplete CRS, poor performance status, or progression on systemic chemotherapy.
METHODS
A retrospective analysis of patients undergoing CRS + HIPEC for peritoneal mesothelioma and receiving OMCT for poor risk factors.
RESULTS
Sixteen patients underwent CRS + HIPEC between 2013 and 2017. The median PCI was 31.5. Complete cytoreduction (CC-0/1) was obtained in 8 patients (50%). All 16 received HIPEC except one patient with baseline renal dysfunction.Thirteen patients had PCI > 20 where only 5 had CC-0/1. Of 8 suboptimal cytoreduction (CC-2/3), 7 received OMCT (6 for progression on chemotherapy and one for mixed histology). Three patients had PCI < 20 and all had CC-0/1 clearance. Only one received OMCT for progression on adjuvant chemotherapy. Patients receiving OMCT for progression on adjuvant chemotherapy (ACT) were in poor PS.The median follow-up was 13.4 months. Five are alive with the disease (three are on OMCT). Six are alive without disease (2 are on OMCT). The mean OS was 24.3 months and the mean DFS was 18 months. Outcomes were similar between CC-0/1 and CC-2/3 groups, OMCT vs no OMCT groups.All patients receiving OMCT for progression on neoadjuvant chemotherapy had better survival (alive at 12, 20, 32, 36 months) compared to those receiving OMCT for progression on the ACT ( = 0.012).
CONCLUSION
OMCT is a good alternative in high-volume peritoneal mesothelioma with incomplete cytoreduction and progression on chemotherapy. OMCT may improve outcomes in these scenarios when started early.
PubMed: 37359939
DOI: 10.1007/s13193-022-01691-8 -
Cancer Science Sep 2023The present study proposes metronomic chemotherapy (CPT), including prednisolone, cyclophosphamide, and thalidomide, as a treatment for patients with severe symptomatic...
The present study proposes metronomic chemotherapy (CPT), including prednisolone, cyclophosphamide, and thalidomide, as a treatment for patients with severe symptomatic indolent T‐cell lymphoproliferative disorder of the gastrointestinal tract. The encouraging efficacy and excellent safety profile of CPT suggest the clinical potential of this combination.
Topics: Humans; Gastrointestinal Tract; Lymphoma, T-Cell; T-Lymphocytes; Lymphoproliferative Disorders
PubMed: 37340510
DOI: 10.1111/cas.15880 -
The Journal of Experimental Medicine Jul 2023
PubMed: 37339062
DOI: 10.1084/jem.2015166506142023c -
Frontiers in Oncology 2023Peripheral T-cell lymphoma (PTCL) is a rare and heterogenous hematologic malignancy with poor prognosis especially in elderly and frail patients who are not eligible for...
PURPOSE
Peripheral T-cell lymphoma (PTCL) is a rare and heterogenous hematologic malignancy with poor prognosis especially in elderly and frail patients who are not eligible for intensive treatment. The resulting palliative setting necessitates tolerable but effective schedules for outpatient treatment. TEPIP is a locally developed, all-oral low-dose regimen comprising trofosfamide, etoposide, procarbazine, idarubicin, and prednisolone.
METHODS
In this observational retrospective, single-center study, the safety and efficacy of TEPIP was evaluated in 12 patients (pts.) with PTCL treated at the University Medical Center Regensburg between 2010 and 2022. The endpoints were overall response rate (ORR) and overall survival (OS), and adverse events were individually reported according to the Common Terminology Criteria for Adverse Events (CTCAE) criteria.
RESULTS
The enrolled cohort was characterized by advanced age (median 70 years), extensive disease (100% Ann Arbor ≥stage 3), and poor prognosis (75% high/high-intermediate international prognostic index). The most common subtype was angioimmunoblastic T-cell lymphoma (8/12), and 11/12 patients had relapsed or refractory disease at TEPIP onset with a median of 1.5 prior treatment regimens. After a median of 2.5 TEPIP cycles (total of 83 cycles), the ORR was 42% (complete remission 25%), and the OS reached a median of 185 days. Any grade of adverse event (AE) occurred in 8/12 patients, with four patients showing AE ≥CTCAE grade 3 (33%), and the AEs were mainly non-hematological.
CONCLUSION
TEPIP demonstrated competitive efficacy with a tolerable safety profile in a highly palliative cohort of patients with difficult-to-treat PTCL. The all-oral application, which makes outpatient treatment possible, is particularly noteworthy.
PubMed: 37305564
DOI: 10.3389/fonc.2023.1177330 -
Cells Jun 2023Alternative therapies such as photodynamic therapy (PDT) that combine light, oxygen and photosensitizers (PSs) have been proposed for glioblastoma (GBM) management to...
Alternative therapies such as photodynamic therapy (PDT) that combine light, oxygen and photosensitizers (PSs) have been proposed for glioblastoma (GBM) management to overcome conventional treatment issues. An important disadvantage of PDT using a high light irradiance (fluence rate) (cPDT) is the abrupt oxygen consumption that leads to resistance to the treatment. PDT metronomic regimens (mPDT) involving administering light at a low irradiation intensity over a relatively long period of time could be an alternative to circumvent the limitations of conventional PDT protocols. The main objective of the present work was to compare the effectiveness of PDT with an advanced PS based on conjugated polymer nanoparticles (CPN) developed by our group in two irradiation modalities: cPDT and mPDT. The in vitro evaluation was carried out based on cell viability, the impact on the macrophage population of the tumor microenvironment in co-culture conditions and the modulation of HIF-1α as an indirect indicator of oxygen consumption. mPDT regimens with CPNs resulted in more effective cell death, a lower activation of molecular pathways of therapeutic resistance and macrophage polarization towards an antitumoral phenotype. Additionally, mPDT was tested in a GBM heterotopic mouse model, confirming its good performance with promising tumor growth inhibition and apoptotic cell death induction.
Topics: Mice; Animals; Glioblastoma; Photochemotherapy; Polymers; Tumor Microenvironment; Cell Line, Tumor; Nanoparticles
PubMed: 37296661
DOI: 10.3390/cells12111541 -
PLoS Computational Biology Jun 2023Implementation of effective cancer treatment strategies requires consideration of how the spatiotemporal heterogeneities within the tumor microenvironment (TME)...
Implementation of effective cancer treatment strategies requires consideration of how the spatiotemporal heterogeneities within the tumor microenvironment (TME) influence tumor progression and treatment response. Here, we developed a multi-scale three-dimensional mathematical model of the TME to simulate tumor growth and angiogenesis and then employed the model to evaluate an array of single and combination therapy approaches. Treatments included maximum tolerated dose or metronomic (i.e., frequent low doses) scheduling of anti-cancer drugs combined with anti-angiogenic therapy. The results show that metronomic therapy normalizes the tumor vasculature to improve drug delivery, modulates cancer metabolism, decreases interstitial fluid pressure and decreases cancer cell invasion. Further, we find that combining an anti-cancer drug with anti-angiogenic treatment enhances tumor killing and reduces drug accumulation in normal tissues. We also show that combined anti-angiogenic and anti-cancer drugs can decrease cancer invasiveness and normalize the cancer metabolic microenvironment leading to reduced hypoxia and hypoglycemia. Our model simulations suggest that vessel normalization combined with metronomic cytotoxic therapy has beneficial effects by enhancing tumor killing and limiting normal tissue toxicity.
Topics: Humans; Pharmaceutical Preparations; Angiogenesis Inhibitors; Neoplasms; Antineoplastic Agents; Immunotherapy; Neovascularization, Pathologic; Tumor Microenvironment
PubMed: 37289729
DOI: 10.1371/journal.pcbi.1011131 -
Frontiers in Oncology 2023We retrospectively analyzed the effective and safety of continuous low-dose cyclophosphamide combined with prednisone (CP) in relapsed and refractory multiple myeloma...
BACKGROUND/OBJECTIVE
We retrospectively analyzed the effective and safety of continuous low-dose cyclophosphamide combined with prednisone (CP) in relapsed and refractory multiple myeloma (RRMM) patients with severe complications.
METHODS
A total of 130 RRMM patients with severe complications were enrolled in this study, among which 41 patients were further given bortezomib, lenalidomide, thalidomide or ixazomib on the basis of CP regimen (CP+X group). The response to therapy, adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were recorded.
RESULTS
Among the 130 patients, 128 patients received therapeutic response assessment, with a complete remission rate (CRR) and objective response rate (ORR) of 4.7% and 58.6%, respectively. The median OS and PFS time were (38.0 ± 3.6) and (22.9±5.2) months, respectively. The most common AEs were hyperglycemia (7.7%), pneumonia (6.2%) and Cushing's syndrome (5.4%). In addition, we found the pro-BNP/BNP level was obviously decreased while the LVEF (left ventricular ejection fraction) was increased in RRMM patients following CP treatment as compared with those before treatment. Furthermore, CP+X regimen further improved the CRR compared with that before receiving the CP+X regimen (24.4% . 2.4%, =0.007). Also, both the OS and PFS rates were significantly elevated in patients received CP+X regimen following CP regimen as compared with the patients received CP regimen only.
CONCLUSION
This study demonstrates the metronomic chemotherapy regimen of CP is effective to RRMM patients with severe complications.
PubMed: 37284198
DOI: 10.3389/fonc.2023.1185991 -
Breast Care (Basel, Switzerland) May 2023Metronomic chemotherapy (MCT) is increasingly used in oncology due to its favorable therapeutic index. There is still a lack of evidence for MCT in metastatic breast...
INTRODUCTION
Metronomic chemotherapy (MCT) is increasingly used in oncology due to its favorable therapeutic index. There is still a lack of evidence for MCT in metastatic breast cancer (MBC). In this retrospective unicenter study, we demonstrated real-word data on MCT in MBC.
METHODS
MBC patients who received metronomic oral cyclophosphamide (CTX) (50 mg daily) and methotrexate (MTX) (2.5 mg every other day), CTX and capecitabine (CAPE) (500 mg thrice daily), CTX, or vinorelbine (VRL) (30 mg daily) alone for at least 4 weeks between 2009 and 2021 were included. The primary endpoint was disease control rate (DCR) ≥24 weeks. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Patient characteristics and therapy response were analyzed using χ test. For survival analyses, Kaplan-Meier estimator and log-rank test were used.
RESULTS
Seventy-two patients were identified. Sixty-two patients received CTX/MTX, three CTX/CAPE, two CTX, and five VRL. Median age at diagnosis MBC and at start of MCT was 59.0 years and 64.5 years, respectively. 72.2% tumors were hormone receptor positive and 27.8% were triple-negative. 54.2% patients had more than two different metastases. 80.6% patients showed visceral involvement. 31.9% patients achieved DCR ≥24 weeks. Median PFS was 17.0 weeks (95% CI 14.5-19.5) and median OS was 58.0 weeks (95% CI 29.0-87.0). MCT showed similar DCR ≥24 weeks and clinically meaningful but not statistically significant shorter median PFS compared to prior therapy (31.9% versus 32.8% [ = 0.570] and 17.0 weeks versus 20.0 weeks [ = 0.093], respectively) and statistically significant higher DCR ≥24 weeks and longer median PFS compared to subsequent therapy (31.9% versus 17.4% [ = 0.038] and 17.0 weeks versus 12.0 weeks [ = 0.006], respectively). Three (4.2%) patients terminated MCT because of toxicity.
CONCLUSION
In this real-world retrospective study, MCT was effective and well tolerated and may thus represent a valuable treatment option in selected MBC patients.
PubMed: 37261128
DOI: 10.1159/000528042 -
Frontiers in Pharmacology 2023Metronomic maintenance therapy (MMT) has significantly improved the survival of patients with high-risk rhabdomyosarcoma in clinical trials. However, there remains a...
Metronomic maintenance therapy (MMT) has significantly improved the survival of patients with high-risk rhabdomyosarcoma in clinical trials. However, there remains a lack of relevant data on its effectiveness in real-world situations. We retrospectively retrieved data of 459 patients < 18 years of age diagnosed with rhabdomyosarcoma at Sun Yat-sen University Cancer Center from January 2011 to July 2020 from our database. The MMT regimen was oral vinorelbine 25-40 mg/m for twelve 4-week cycles on days 1, 8, and 15, and oral cyclophosphamide 25-50 mg/m daily for 48 consecutive weeks. A total of 57 patients who underwent MMT were included in the analysis. The median follow-up time was 27.8 (range: 2.9-117.5) months. From MMT to the end of follow-up, the 3-year PFS and OS rates were 40.6% ± 6.8% and 58.3% ± 7.2%, respectively. The 3-year PFS was 43.6% ± 11.3% in patients who were initially diagnosed as low- and intermediate-risk but relapsed after comprehensive treatment (20/57), compared with 27.8% ± 10.4% in high-risk patients (20/57) and 52.8% ± 13.3% in intermediate-risk patients who did not relapse (17/57). The corresponding 3-year OS for these three groups was 65.8% ± 11.4%, 50.1% ± 12.9%, and 55.6% ± 13.6%, respectively. We present a novel study of MMT with oral vinorelbine and continuous low doses of cyclophosphamide in real-world pediatric patients with RMS. Our findings showed that the MMT strategy significantly improved patient outcomes and may be an effective treatment for high-risk and relapsed patients.
PubMed: 37205905
DOI: 10.3389/fphar.2023.1132219