combined chemotherapy
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2021 ◽  
Vol 21 (12) ◽  
pp. 6196-6204
Author(s):  
Shu Wen ◽  
Weiping Xing ◽  
Lingxue Gao ◽  
Shuping Zhao

This study aimed to investigate the effects of DMSO@γ-Fe2O3 nanomagnetic fluid thermotherapy combined with the chemotherapy drug carmustine on cervical cancer cells under a certain intensity of alternating magnetic field. And the role of Mir-590-3P in the development and progression of cervical cancer. The optimal thermotherapy concentration of γ-Fe2O3 nanomaterials on cervical cancer cells was determined by in vitro heating. In addition, the MTT colorimetric method was used to evaluate the toxic effect of γ-Fe2O3 magnetic nanoparticles on cervical cancer cells, and the optimal therapeutic concentration of carbachol on cervical cancer cells was optimized (0.015 g · L−1). The cervical cancer cells were divided into control, γ-Fe2O3 hyperthermia, chemotherapy, and DMSO@γ-Fe2O3 combined chemotherapy groups. After 2 h exposure to hypothermic conditions, flow cytometry was used to assess cell apoptosis for each group. The heating effect of the γ-Fe2O3 magnetic nanomaterials was apparent. When the concentration of γ-Fe2O3 was ≥6 g· L−1, the temperature rise above 41 °C. γ-Fe2O3 is non-toxic to cervical cancer cells and has good biocompatibility. Taking the drug concentration of IC25 as the working concentration of this study, the working concentration of carmustine was 0.015 g · L−1. Both the 41 °C heat treatment and chemotherapy alone had a killing effect on glioma and cervical cancer cells (P < 0.05). Additionally, the combined inhibitory effect of DMSO@γ-Fe2O3 nanomagnetic fluid thermotherapy and drugs at this temperature was significantly stronger than that of thermotherapy and chemotherapy alone (P < 0.05). For the control, gamma-Fe2O3 hyperthermia, chemotherapy, and DMSO@γ-Fe2O3 combined chemotherapy groups, the apoptosis rates of the cervical cancer cells were 1.4%, 18.6%, 24.12%, and 38.97%, respectively. DMSO@γ-Fe2O3 nanomagnetic fluid thermotherapy combined with the chemotherapeutic drug carmustine exerted a noticeable toxic effect on the cervical cancer cells, and DMSO@γ-Fe2O3 significantly enhanced the killing effect of carmustine on cervical cancer cells.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Weiwei Liu ◽  
Xiaoping Ye ◽  
Lingyun He ◽  
Juan Cheng ◽  
Wenpei Luo ◽  
...  

Abstract Background Distant metastasis to vital organs is the major contributor to breast cancer mortality, and regional lymph node metastasis is an important facilitator of distant metastasis and recurrence in this cancer. The early diagnosis and precise treatment of lymph node metastasis are crucial for staging and prognosis in breast cancer. Herein, we report a visualized precision medicine nanoplatform of metastatic lymph nodes for ultrasonic/photoacoustic (US/PA) dual modal imaging-guided in situ targeted hyperthermia-combined chemotherapy. Results Carbon nanoparticles (CNs), approved by the China Food and Drug Administration, were loaded with docetaxel and rationally combined with anti-hypoxia-inducible factor 1α antibody-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles to achieve the combination of passive targeting at the lymph nodes and intracellular targeting at HIF 1α factor. The accumulation and retention of nanoparticles in metastatic lymph nodes via lymphatic delivery were enhanced. Docetaxel could be effectively offloaded by CNs that have active carbon nanoparticles, and the PLGA membrane prevented drug leakage. The nanoparticles exhibited excellent photothermal performance with a photothermal conversion efficiency of 28.9%, killing tumor cells in metastatic lymph nodes through hyperthermia. In vitro and in vivo systematic evaluations revealed that hyperpyrexia triggered the rupture of nanoparticles caused by the phase transition of perfluorohexane, resulting in docetaxel release for achieving in situ hyperthermia-combined chemotherapy. Conclusions The laser-triggered highly efficient in situ chemotherapy nanosystem achieves targeted synergistic chemo-hyperthermia treatment of metastatic lymph nodes, and lymphatic delivery represents a strategy to avoid additional injury caused by drugs entering the blood circulation. Graphical Abstract


2021 ◽  
pp. 1671-1676
Author(s):  
Hideko Hoshina ◽  
Hiroyuki Takei

Drug-induced interstitial lung disease (DILD) has been occasionally reported with various causative drugs. In the context of breast cancer, anthracycline infrequently causes pulmonary adverse events. We report a 67-year-old woman with cT2N0M0 triple-negative breast cancer who received neoadjuvant chemotherapy with anthracycline-combined chemotherapy with pegfilgrastim. She developed fever, cough, and shortness of breath after 21 days of the scheduled fourth cycle of anthracycline. Computed tomography revealed drug-induced interstitial pneumonia. Prednisolone (1 mg/kg) was administrated and gradually decreased. Thereby, interstitial pneumonia quickly improved. Partial resection of the left breast and sentinel lymph node biopsy were performed, and we diagnosed ypT1bN0. The patient received 4 cycles of taxane and hypofractional radiotherapy and survived without any recurrences over the following 37 months. We report a rare case of DILD due to anthracycline-combined chemotherapy. Twenty-five cases of DILD with breast cancer after administration of anthracycline have been reported so far. However, 14 cases occurred during taxane. Most of the cases had remission by steroid treatment. The patients with respiratory symptoms during chemotherapy should be suspicious of not only infection but also DILD.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4741-4741
Author(s):  
Fang Fang ◽  
Guoxiang Wang ◽  
Ronghua Hu ◽  
Wuhan Hui ◽  
Hong Zhao ◽  
...  

Abstract Background:There is no standard treatment recommendation for POMES syndrome, a rare clonal plasm cell disease. Although autologous hematopoietic stem cell transplantation (ASCT) has been considered to have advantage in remission rate and long-term survival, but in most newly diagnosed cases, it is not applicable to conduct ASCT directly because of the severity of patients' conditions. Combined chemotherapy, applied in other plasm cell disorder, is a choice for POEMS syndrome. Both melphalan and lenalidomide have been proved to be effective in POEMS syndrome, but the long-term administration of these agents might damage hematopoietic stem cells and result in failure of stem cell mobilization. Proteasome inhibitor, bortezomib based regimen is also the first-line treatment in other plasm cell dyscrasia. In this study, we investigated and evaluated the effect and safety of the bortezomib-based combined chemotherapy in newly diagnosed POEMS syndrome patients. Method: POEMS syndrome patients newly diagnosed from July 2013 to August 2020 in Xuanwu hospital, Capital Medical University, were enrolled. Informed consent was obtained. Four cycles of Bortezomib-based 28-day BCD regimen (bortezomib 1.3mg/m 2 sc d1,8,15,22, cyclophosphamide iv 0.4g/m 2 d1,15, dexamethasone 40mg iv d1,8,15,22) were used as induction therapy. After the induction, ASCT or another two cycles of BCD therapy were conducted as consolidation therapy. Patients diagnosed in the same period but refusing bortezomib were treated with CD/CTD regimen (the same as BCD without bortezomib), and thalidomide 50-100mg once daily was suggested if it was well-tolerated. (Figure A) Results: There were totally 22 newly diagnosed POEMS syndrome patients accepted BCD regimen, and 16 patients CD/CTD regimen. First of all, the response rate in BCD group was superior to CD/CTD group, no matter the VEGF remission rate or hematologic complete remission rate (Figure B1-B4). The median time to achieve VEGF CR was 133 days in BCD group and 214 days in CD/CTD group. The median time to achieve hematologic remission was 218 days in BCD group and 415 days in CD/CTD group. Secondly, the improvement of neurologic symptoms in BCD group was not inferior to CD/CTD group. Bortezomib was well tolerated and didn't deteriorate the polyneuropathy (Figure C1-C3). Thirdly, during the median 35 months follow-up, the overall 5-year OS of 31 patients was 93.55%, 3-year and 5-year PFS were 83.47% and 76.51% respectively (Figure D1-D2). The 5-year-OS and 3-year and 5-year PFS of BCD group were superior to CD/CTD group (Figure D3-D4). In the consideration of ASCT significantly improve OS and PFS in POEMS syndrome patients, the long-term survival results were analyzed among ASCT group and cheotherapy only groups. The BCD+ASCT group achieved a best 5-year OS and 3-year and 5-year PFS (Figure D5-D6). Fourthly, about 54% of male patients had a subnormal testosterone at diagnosis, with normal or slightly elevated LH. After treatment, testosterone returned to normal level in male patients with the VEGF CR and VEGF PR (Figure E1). And the median remission time of testosterone was 76 days, which was earlier than that of VEGF remission was 143 days. The testosterone returned to normal after two cycle treatment predicted a better PFS. (Figure E2). About 86% of men at diagnosis had elevated estradiol which is the most common gonadal hormone abnormalities. After treatment, patients with better treatment response would have lower estradiol level (Figure E3-E4). Estradiol less than 58pg/ml after two cycle treatment and estradiol less than 48pg/ml after four cycle treatment predicted a better 5-year PFS (FigureE5-E6). After four cycle treatment, slightly elevated estradiol (48-79pg/ml) may be at risk for later recurrence and significant elevated estradiol tended to progress early (Figure E5). In women, low LH was frequently observed. Two patients with persistent low LH died within 1 year of diagnosis. Persistent low LH level in female patients may be an important predictor for poor prognosis. Conclusion: Bortezomib-based BCD regimen in newly diagnosed POEMS syndrome patients seems improve the response rate and survival, especially in patients with sequential ASCT. Recovery of gonadal hormone level might be a potential marker for response and prognosis. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2461-2461
Author(s):  
Kaiyang Ding ◽  
Xiao Shi ◽  
Haiyan Yang ◽  
Lei Cao ◽  
Xiaoli Zhao ◽  
...  

Abstract Introduction Peripheral T-cell lymphoma (PTCL) is a group of hematological malignancies originating from mature T/NK cells. Most of the subtypes are associated with aggressive clinical features and dismal outcomes. Routine first-line chemotherapy has low efficiency and a high recurrence rate, so there is an urgent need for new drugs. Monotherapy or combination therapy of epigenetic inhibitors have been shown to be effective in several hematologic malignancies. Here, we report the interim efficacy of an epigenetic priming regimen with azacytidine and chidamide prior to salvage chemotherapy for relapsed or refractory (R/R) PTCL. Methods The prospective phase II study (ChiCTR2000037232) enrolled pts were pathologically confirmed T/NK cell non-Hodgkin's lymphoma with at least one imaging measurable lesion. Pts needed to have received at least one systemic chemotherapy regimen including hematopoietic stem cell transplantation, radiotherapy, or a single epigenetic drug. Pts received AZA hypodermically at a dose of 100 mg on days 1 to 7, chidamide of 20 mg orally twice per week; the combined chemotherapy regimens included but were not limited to GemOx (gemcitabine, oxaliplatin); CPT (cyclophosphamide, prednisone, thalidomide) , etc. Treatment was performed for up to eight cycles of each 21 days. Pts who achieved partial response (PR) and better remission began maintenance therapy every two months with double epigenetic inhibitors for two years. The trial aimed to explore the efficacy and safety of AZA and chidamide combined chemotherapy in the treatment of R/R PTCL. The primary objective was investigator-assessed best overall response rate (ORR). Secondary objectives included duration of response (DOR), complete response rate (CRR), progression-free survival (PFS), overall survival (OS), and safety profiles. Results A total of 24 pts have been enrolled, baseline characteristics are shown in Table 1. Pathological subtypes included angioimmunoblastic T-cell lymphoma(AITL, n=15), PTCL-not otherwise specified (PTCL-NOS, n=4), extranodal NK/T-cell lymphoma (ENKTCL, n=3) and mycosis fungoides(MF, n=2). The median age was 57 (range,38-72) years with male predominance. Ann Arbor Classification ≥ stage III in 20 pts. Twelve pts had B symptoms at the time of diagnosis, five pts had performance status ≥ 3 before treatment. The median number of previous systemic treatment regimens was two. Autologous hematopoietic stem cell transplantation in two pts, radiation in three pts and prior treatments containing chidamide in eight pts. At the time of data cutoff, the median number of treatments for all pts was four cycles (range,1-13). Among 16 pts evaluable for response, the best ORR was 68.8% (11/16) with five pts achieved CR, six achieved PR. In subgroup analysis, eleven AITL pts achieved an objective response. The best ORR was 72.7% (8/11) with four pts attained CR, four attained PR (Table 2). The median follow-up was 12.4 (range, 0.1-18.7) months. For all pts, the median PFS was 6.7 months (95% CI,5.8-7.6), the median OS was 8.4 months (95% CI,0.0-18.3) (Figure 1). And the median DOR was 10.2 months (95% CI,4.9-15.5). For AITL pts, the median PFS was 14.6 months (95% CI,3.6-25.6), and the median OS was not reached (Figure 2). The OS between AITL and other subtypes pts was statistically significant (1-year OS: 76.2% vs 13.9%; p=0.003, Figure 3). Almost all pts had experienced at least one adverse event (AE). The most common grade 3 or 4 AEs were anemia, leukopenia, neutropenia, thrombocytopenia, and infections. Conclusions Epigenetic priming regimen with azacitidine plus chidamide with salvage chemotherapy is effective and tolerable. The best ORR of all enrolled pts with AITL were 68.8% and 72.7%, respectively. Compare to other subtypes, patients with AITL subtype benefit more obviously from our regimen with durable remission. And further studies will focus on patients with AITL and follicular helper T-cell originated. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4588-4588
Author(s):  
Vasile Musteata ◽  
Lilian Nichifor ◽  
Larisa Musteata ◽  
Galina Durbailova

Abstract Background: Non-Hodgkin lymphomas (NHL) comprise a variety of lymphoproliferative malignancies with certain differences related to the morphological, clinical, immunohistochemical and hematological patterns, as well as the results of treatment. The patients with generalized and relapsed nasopharyngeal NHL experience marked disease burden and unfavorable impact on their life quality and working capacity. Objective: The aim of the study was to characterize the diagnosis issues of NHL with primary involvement of the nasopharynx and evaluate the short- and long-term results of management options. Materials and methods: This analytical and cohort study included 66 patients with different stages of nasopharyngeal NHL, who were managed at the Institute of Oncology from Moldova between 2014-2021. The diagnosis was confirmed by cytological, histopathological and immunohistochemical examinations. The histological types of NHL were verified and distinguished according to the 2017 Revision of WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. The patients treatment, follow-up and researches were realized at the comprehensive cancer center. The study was related to the hospitalized care. The patients age ranged between 19-85 years (average age - 58.4±2,14 years). Males were 28 (42%), females - 38 (58%). Stage I NHL was diagnosed in 10 (15.2%) cases, stage II - in 36 (54.5%), stage III - in 8 (12.1%) and stage IV - in 12 (18.2%). The eligible NHL patients underwent combined chemotherapy (CChT) regimens (CVChlP, R-CVChlP, CHOP and R-CHOP), associated with radiotherapy locoregional treatment in cases of bulky disease or residual tumor masses. The ECOG-WHO score and complete response (CR) rate assessed the short-term results. The long-term results were asserted by the overall one- and 5-year survival. Results: Primary nasopharyngeal NHL occurred commonly in females (58%) and in patients over 60 years (42.4%). The ECOG-WHO score accounted 1-3 at diagnosis. The aggressive NHL were diagnosed mostly (76.1%) in stage I and II due to the earlier developed disease burden. The primary tumor site was localized in the palatine tonsils in 22 (33.3%) patients, in 33 (50%) patients in the pharyngeal tonsil, in 2 (3%) patients in the lingual tonsil. The palatine and pharyngeal tonsils were concomitantly involved in 9 (13.7%) patients. Palatine tonsil involvement occurred mostly in patients over 60 years old, and pharyngeal tonsil involvement - in patients of 40-59 years. CR was achieved in 10 (100%) cases with stage I after combined chemotherapy (CChT) and radiotherapy locoregional treatment. CR occurred in 21 (67.7%), partial response (PR) - in 7 (22.6%) and response failure (RF) - in 3 (9.7%) in stage II NHL after CChT and radiotherapy locoregional treatment. In stage II NHL treated with CChT along, CR was achieved in 1 (25%), PR - in 2 (50%) and RF in 1 (25%). In stage III treated with CChT and radiotherapy locoregional treatment, CR was registered in 1 (20%), PR - in 2 (40%) and RF - in 2 (40%). PR occurred in 2 (66.7%), RF - in 1 (33.3%) in stage III managed with CChT alone. In stage IV NHL, CR was obtained 1 (11.1%) case, PR - in 5 (55.6%), RF - in 3 (33.3%) after CChT and radiotherapy locoregional treatment. PR occurred in 1 (33.3%), RF - in 2 (66.7%) cases in stage IV patients managed with CChT alone. No significant differences of CR rate were found in stage III (12,5%) and stage IV (8.3%) NHL (P&gt;0.05). Irrespective of the stage, the highest CR rate was registered after CChT and radiotherapy locoregional treatment (97.1% of all cases), as compared to CChT alone (2.9% of all cases). The ECOG-WHO score reached 0-1 under the management with CChT and radiotherapy locoregional treatment in all cases with CR and PR. The overall survival was 79.9% at one year and 34.5% at 5 years. One- and 5-year survival proved to be significantly higher în stage I and II NHL - 96.1% and 64.2% respectively. One- and 5-year survival was 79.9% and 34.5% in stage III and IV NHL. Conclusions: Primary nasopharyngeal NHL were outlined by the predominant involvement of females, patients over 60 years and frequent site in the pharyngeal tonsil. The aggressive NHL were revealed commonly in stage I and II due to the progressive disease burden. The rates of the indolent and aggressive NHL turned out to be statistically equal in stage III and IV. The response and overall survival rates proved to be superior after R-CHOP regimen followed by the radiotherapy locoregional treatment. Disclosures No relevant conflicts of interest to declare.


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