Objective: To evaluate the efficacy and safety of different medical treatment in advanced or unresectable angiosarcoma. Methods: This study was a single-center retrospective clinical study. Fifty-five advanced or unresectable angiosarcoma patients treated in Sun-Yat Sen University Cancer Center from January 2005 to August 2020 were enrolled. There were 34 patients who received first-line doxorubicin-based chemotherapy (doxorubicin group), 12 patients received first-line doxorubicin or liposome doxorubicin plus paclitaxel or albumin bound paclitaxel chemotherapy (combination therapy group), and 4 patients received first-line paclitaxel-based treatment (paclitaxel group). There were 6 patients who received anti-angiogenesis targeted therapy, another 2 patients received anti-PD-1 antibody plus anti-angiogenesis targeted therapy. Targeted therapy and immunotherapy plus targeted therapy included 5 cases of first-line therapy and 3 cases of second-line therapy. The therapeutic effect was evaluated by RECIST 1.1 standard. The adverse reactions were evaluated by CTCAE4.0 standard. Kaplan-Meier survival analysis was evaluated with Log rank test. Cox proportional hazard model was used to analyze the influencing factors. Results: There were 18 patients achieved partial response (PR) in 34 patients in the doxorubicin group, median progression-free survival (mPFS) was 4.5 months, and median overall survival (mOS) was 15 months. Four patients achieved PR in 12 patients in the combination therapy group, mPFS and mOS were 4 months and 19 months. Two patients achieved PR in 4 patients in the paclitaxel group, mPFS and mOS were 3 months and 9 months. However, only 1 in 6 patients achieved PR for anti-angiogenesis targeted therapy, mPFS and mOS were 3 months and 16 months. Two patients who received anti-PD-1 immunotherapy combined with anti-angiogenesis targeted therapy acquired PR for 17 months and more than 16 months. Median PFS (7.5 months) were longer in those with primary liver, lung and spleen angiosarcoma than in those with other primary site (3.0 months, P=0.028). The mOS (20 months) was longer in females than that in males (12 months, P=0.045). Primary tumor site, sex, age and treatment were not independent prognostic factors for angiosarcoma patients (P>0.05). Grade 3-4 cardiac toxicity was found in 2 patients in the combination therapy group. Conclusions: Doxorubicin-based and paclitaxel-based chemotherapy are the most important treatment for advanced angiosarcoma. Potential efficacy for targeted therapy combined with anti-PD-1 immunotherapy are showed in some patients with long duration of response and moderate adverse event.
Male ; Female ; Humans ; Hemangiosarcoma ; Retrospective Studies ; Paclitaxel/adverse effects* ; Doxorubicin/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*

Angioplasty, Balloon, Coronary ; adverse effects ; methods ; Drug-Eluting Stents ; Humans ; Paclitaxel ; therapeutic use

Adult ; Coronary Aneurysm ; etiology ; Drug-Eluting Stents ; adverse effects ; Humans ; Male ; Paclitaxel ; therapeutic use

Objective: To explore the efficacy and safety of real-world eribulin in the treatment of metastatic breast cancer. Methods: From December 2019 to December 2020, patients with advanced breast cancer were selected from Beijing Chaoyang District Sanhuan Cancer Hospital, Shandong Cancer Hospital, Peking University Cancer Hospital, Baotou Cancer Hospital, Shengjing Hospital Affiliated to China Medical University, and Cancer Hospital of Chinese Academy of Medical Sciences. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: The median progression-free survival (PFS) of 77 patients was 5 months, the objective response rate (ORR) was 33.8%, and the disease control rate (DCR) was 71.4%. The ORR of patients with triple-negative breast cancer was 23.1%, and the DCR was 57.7%; the ORR of patients with Luminal breast cancer was 40.0%, and the DCR was 77.8%; the ORR of patients with HER-2 overexpression breast cancer was 33.3%, and the DCR was 83.3%. ORR of 50.0% and DCR of 66.7% for patients treated with eribulin as first to second line treatment, ORR of 29.4% and DCR of 76.5% for patients treated with third to fourth line and ORR of 28.6% and DCR of 71.4% for patients treated with five to eleven line. The ORR of patients in the eribulin monotherapy group was 40.0% and the DCR was 66.0%; the ORR of patients in the combination chemotherapy or targeted therapy group was 22.2% and the DCR was 81.5%. Patients with a history of treatment with paclitaxel, docetaxel, or albumin paclitaxel during the adjuvant phase or after recurrent metastasis had an ORR of 32.9% and a DCR of 69.9% when treated with eribulin. The treatment efficacy is an independent prognostic factor affecting patient survival (P<0.001). The main adverse reactions in the whole group of patients were Grade Ⅲ-Ⅳ neutrophil decline [29.9% (23/77)], and other adverse reactions were Grade Ⅲ-Ⅳ fatigue [5.2% (4/77)], Grade Ⅲ-Ⅳ peripheral nerve abnormality [2.6% (2/77)] and Grade Ⅲ-Ⅳ alopecia [2.6% (2/77)]. Conclusions: Eribulin still has good antitumor activity against various molecular subtypes of breast cancer and advanced breast cancer that has failed multiple lines of chemotherapy, and the adverse effects can be controlled, so it has a good clinical application value.
Breast Neoplasms/pathology* ; Female ; Furans/adverse effects* ; Humans ; Ketones/adverse effects* ; Paclitaxel/adverse effects* ; Treatment Outcome ; Triple Negative Breast Neoplasms/drug therapy*

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
Humans ; Female ; Breast Neoplasms/chemically induced* ; Paclitaxel/adverse effects* ; Liposomes/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Trastuzumab/therapeutic use* ; Capecitabine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*

AIMTo evaluate the hypersensitivity reaction of the blank paclitaxel microemulsion and study the O/W paclitaxel microemulsion's pharmacokinetics in rats.

METHODSAn alternative paclitaxel microemulsion was prepared with small particle size. The hypersensitivity reaction of the blank microemulsion was investigated in guinea pigs. In pharmacokinetic study, 5 rats were given i.v. Taxol or paclitaxel microemulsion. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 14 h and the concentration of paclitaxel in plasma was determined by HPLC method. The data obtained were processed using 3P87 program.

RESULTSThe mean size of the microemulsion is 17.2 nm. The preparation of blank microemulsion did not show any hypersensitivity, while the injection of commercial product showed significant hypersensitivity. The concentration-time curve of paclitaxel microemulsion and commercial injection (Taxol) fitted a two-compartment model. The K10, K12, K21 and AUC of paclitaxel microemulsion were 0.571.h-1, 1.441.h-1, 3.081.h-1 and 34.98 mg.h.L-1. Those of commercial injection were 1.291.h-1, 1.271.h-1, 0.511.h-1 and 21.85 mg.h.L-1.

CONCLUSIONThe blank paclitaxel preparation of micoemulsion reduced the hypersensitivity in guinea pigs compared with the blank commercial injection. The paclitaxel microemulsion has relatively longer circulating time in rats.

Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; adverse effects ; pharmacokinetics ; Drug Hypersensitivity ; etiology ; Emulsions ; Female ; Guinea Pigs ; Injections, Intravenous ; Male ; Paclitaxel ; administration & dosage ; adverse effects ; pharmacokinetics ; Rats

Antineoplastic Agents, Phytogenic ; adverse effects ; therapeutic use ; Chemical and Drug Induced Liver Injury ; prevention & control ; Female ; Glutathione ; therapeutic use ; Humans ; Male ; Middle Aged ; Paclitaxel ; adverse effects ; therapeutic use

Adult ; Angioplasty, Balloon, Coronary ; methods ; Coronary Aneurysm ; etiology ; Drug Delivery Systems ; Humans ; Male ; Paclitaxel ; administration & dosage ; Stents ; adverse effects

OBJECTIVETo observe the incidence rate of stent thrombosis after implantation of drug-eluting stents (DES) in patients with coronary artery disease (CAD) in the real world.

METHODSA total of 8190 consecutive CAD patients underwent implantation with Cypher or Cypher Select stents (Cordis, USA, n = 2986), TAXUS stents (Boston Scientific Corp., USA, n = 1587) and Chinese Rapamycin eluting stents (Firebird, Microport Medical Company, China, n = 3617) for enrolled in this single center registry study from Dec.2001 to April 2007. One-year follow-up was completed in 5412 patients (2210 Cypher or Cypher select stents, 1238 TAXUS stents and 1964 Firebird stents). Two-year follow-up was finished in 2176 patients (1245 Cypher or Cypher Select stents, 558 TAXUS stents and 373 Firebird stents). 80.1% of all the lesions were the type B2 and type C lesions. All patients were treated with aspirin plus clopidogrel for at least 9 months post DES.

RESULTSAmong 8190 patients, 17 patients had acute stent thrombosis (0.21%): 7 in the Cypher group, 4 in the TAXUS group, 6 in the Firebird group; 23 patients had subacute stent thrombosis (0.28%): 8 in Cypher group, 6 in TAXUS group and 9 in Firebird group. The incidence rate of acute and subacute thrombosis was 0.49% (40/8190) and incidence of thrombosis was similar among the three groups (0.50% in Cypher group, 0.63% in TAXUS group and 0.41% in Firebird group, P > 0.05). One-year follow-up showed that late thrombosis rate was 0.63 % (34/5412) and similar among the groups (0.63% in Cypher group, 0.89% in TAXUS group and 0.46% in Firebird group, P > 0.05). Two-year follow-up showed that late thrombosis rate was 0.74 % (16/2176) and was similar among the 3 groups (0.72% in Cypher group, 0.90% in TAXUS group and 0.54% in Firebird group, P > 0.05).

CONCLUSIONThis study indicates that using the first-generation DES to treat complex coronary lesions is safe and effective and the incidence of late thrombosis remains low (< 1%) under double antiplatelet treatment.

Coronary Artery Disease ; therapy ; Drug-Eluting Stents ; adverse effects ; Follow-Up Studies ; Humans ; Incidence ; Male ; Paclitaxel ; administration & dosage ; Thrombosis ; etiology

BACKGROUNDPaclitaxel, as a first line anti-neoplastic compound, frequently produces long-term pain after tumors have been treated. Clinical manifestations are varied and non-specific. Pathology of the nervous system during the development of the neuropathic pain is unclear. Thus, early diagnosis and treatment is often unsatisfying for patients. This study aimed to promote considerate understanding of the structural alteration of sensory nerves.

METHODSAll rats were simply randomized into 3 groups: paclitaxel group, vehicle group and saline group. An established rat model of paclitaxel-induced peripheral neuropathy (2 mg/kg) was chosen for our research, behavior tests were operated during the procedure of 56 days. All rats were sampled on days 0, 3, 7, 28 and 56. The hind paw plantar skin, sciatic nerves, dorsal root ganglion and attached fibers, and lumbar spinal cord were processed for light and electron microscopy. The differences among 3 groups were analyzed with one-way analysis of variance (ANOVA).

RESULTSWe affirmed that paclitaxel-induced mechano-allodynia and mechano-hyperalgesia occured after a 3-7-day delay, and this pain peaked at day 28 and persisted to day 56. Paclitaxel and vehicle treatment both evoked thermal-hyperalgesia. Paclitaxel-induced axonal and myelin sheath degeneration was evident. At days 3 and 7, significant increases in atypical mitochondria in both myelinated axons and C-fibers of paclitaxel-treated nerves indicated that injured mitochondria correlated to specific paclitaxel-induced neuropathic pain, and the abnormity sustained till day 56. Microtubule was unaffected in myelinated axons or C-fibers in paclitaxel- or vehicle-treated rats. Significant increase of G ratio was evident with paclitaxel injection at days 7 and 28.

CONCLUSIONOur research suggests a causal role for axonal degeneration, abnormalities in axonal mitochondria, and structural modification of axonal microtubules in paclitaxel-induced neuropathic pain, and the abnormal mitochondria could be connected to the chronic neuropathic pain.

Animals ; Antineoplastic Agents, Phytogenic ; adverse effects ; Axons ; drug effects ; metabolism ; Male ; Microtubules ; drug effects ; metabolism ; Mitochondria ; drug effects ; metabolism ; Neuralgia ; chemically induced ; Paclitaxel ; adverse effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley