Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

Objective: To analyze the value of 3-dimensional speckle tracking echocardiograghy (3D-STE) derived strain parameters on the detection of subclinical myocardial deformation alterations in patients with lymphoma treated with anthracycline agents. Methods: This study was a retrospective study. A total of 37 patients with newly diagnosed diffuse large B cell non-Hodgkin lymphoma between December 2012 and December 2014 in Cancer Center, Fudan university were included. 3D-STE strain measurements were performed at baseline (T0),after the completion of two therapy circles (T1) and at the end of anthracycline regimen chemotherapy (Te). Echocardiography images were analyzed on the TTA workstation, and the indexes included left atrial minimum volume (LAVmin), left atrial emptying index (LAEF), left atrial active emptying index (LAAEF), as well as the left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), left atrial global longitudinal strain (LAGLS). The overall left atrioventricular longitudinal strain (LAVGLS) was calculated, which was the sum of the absolute values of LVGLS and LAGLS. The changes of left ventricular strain indexes measured by 3D-STE at different time points of patients were evaluated. Results: Thirty-seven patients with DLBCL, aged (48.3±12.1)years, including 23 males (63.9%), were enrolled. Compared with baseline, LVGLS (T1: (-18.63±4.73)% vs. (-22.13±4.40)%, P=0.001; Te:(-18.26±4.64)% vs. (-22.13±4.40)%, P<0.001), LAGLS (T1: (20.41±5.56)% vs. (23.98±5.59)%, P=0.003; Te: (17.60±3.96)% vs. (23.98±5.59)%, P<0.001) and LAVGLS (T1: (39.05±7.60)% vs. (46.11±7.77)%, P<0.001; Te: (40.34±8.55)% vs. (46.11±7.77)%, P<0.001) were all deteriorated at the T1 and Te. While LVGCS ((-21.98±5.82)% vs. (-26.15±7.51)%, P=0.010), LAVmin ((23.93±7.29)ml vs. (20.33±7.03)ml, P=0.029), LAEF ((28.94±11.16)% vs. (35.79±11.12)%, P=0.002) and LAAEF ((11.93±10.00)% vs. (18.10±9.96)%, P=0.013) were decreased only until Te. Conclusions: 3D-STE strain measurements could detect early myocaridial function alteration in patients receiving anthracycline regimen chemotherapy, thus may provide a novel approach to monitor anthracycline caused myocardial toxicity.
Male ; Humans ; Anthracyclines/therapeutic use* ; Ventricular Function, Left ; Retrospective Studies ; Heart Ventricles ; Antibiotics, Antineoplastic/adverse effects* ; Polyketides/pharmacology* ; Lymphoma/drug therapy*

As a new type of anthracyclines, pegylated liposomal doxorubicin (PLD) is widely used in the treatment of a variety of malignant tumors, including soft tissue sarcoma, ovarian cancer, breast cancer, multiple myeloma, and so on. Compared with traditional anthracyclines, PLD can significantly decrease the incidences of adverse events such as cardiac toxicity and alopecia. However, the use of PLD will be accompanied with toxic side effects such as hand-foot syndrome, oral mucositis, and infusion reaction. This consensus will mainly focus on the mechanism, prevention and treatment of adverse events of PLD, in order to improve the therapeutic efficacy of PLD and life quality of patients.
Antibiotics, Antineoplastic ; adverse effects ; therapeutic use ; Consensus ; Doxorubicin ; adverse effects ; analogs & derivatives ; therapeutic use ; Drug-Related Side Effects and Adverse Reactions ; prevention & control ; Female ; Hand-Foot Syndrome ; complications ; Humans ; Neoplasms ; drug therapy ; Polyethylene Glycols ; adverse effects ; therapeutic use ; Practice Guidelines as Topic ; Stomatitis ; complications

Neamine, a non-toxic derivative of neomycin, has recently been shown to have antitumor activities in various types of cancers. However, its effect on pancreatic cancer is still unknown. The study aimed to investigate its antitumor activity on pancreatic cancer and the underlying mechanisms. MTT assay was used to observe the effect of neamine on angiogenin (ANG)-induced AsPC-1 cell proliferation. Tissue microassay and immunofluorescence staining were used to detect the expression of ANG and its nuclear translocation, respectively. Tumor xenografts were established by subcutaneous inoculation of AsPC-1 pancreatic cancer cells into the right flanks of nude mice, and neamine was injected subcutaneously. Immunohistochemistry was done to observe the expression of ANG, CD31 and Ki-67 in tumor xenografts. It was found that neamine blocked the nuclear translocation of ANG effectively and inhibited ANG-induced AsPC-1 cell proliferation in a dose-dependent manner. Neamine had anti-tumor effects on AsPC-1 xenograft models. Consistently, neamine reduced the expression levels of ANG, Ki-67 and CD31 in tumor xenografts. It was concluded that neamine may be a promising agent for treatment of pancreatic cancer.
Adult ; Animals ; Antibiotics, Antineoplastic ; pharmacology ; therapeutic use ; Carcinoma ; drug therapy ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Framycetin ; pharmacology ; therapeutic use ; Humans ; Ki-67 Antigen ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Pancreatic Neoplasms ; drug therapy ; Platelet Endothelial Cell Adhesion Molecule-1 ; genetics ; metabolism ; Ribonuclease, Pancreatic ; genetics ; metabolism

Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease characterized by hepatocellular inflammation, necrosis, and fibrosis, which can progress to cirrhosis and fulminant hepatic failure. The standard treatment for AIH includes corticosteroids alone or in combination with azathioprine. Although most patients achieve remission using the standard regimen, some patients do not respond due to either drug intolerance or refractory disease; in such cases alternative immunosuppressive agents should be explored. The second-line therapies are cyclophilin inhibitors such as cyclosporine A or tacrolimus, and nowadays mycophenolate mofetil (MMF) is widely used if azathioprine-based therapies are not tolerated. Although these are recommended as an alternative to the first-line regimen, there is insufficient evidence for the efficacy of second-line therapies, with the evidence based mainly on expert opinion. Therefore, we report an AIH patient receiving the standard regimen in whom remission did not occur due to side effects to azathioprine, but was successfully treated with MMF in combination with corticosteroids as an alternative to the standard regimen.
Alanine Transaminase/analysis ; Alopecia/etiology ; Antibiotics, Antineoplastic/*therapeutic use ; Aspartate Aminotransferases/analysis ; Azathioprine/adverse effects ; Female ; Hepatitis, Autoimmune/*drug therapy/pathology ; Humans ; Liver/enzymology/pathology ; Middle Aged ; Mycophenolic Acid/*therapeutic use ; Pancytopenia/etiology ; Prednisolone/therapeutic use

To detect the expressions of human epidermal growth factor receptor 2 (HER2) and Topo IIα in breast cancer, and to analyze the clinical significance of neoadjuvant chemotherapy for the anthracycline-based drugs.
 Methods: The HER2 and Topo IIα gene and protein expressions in cancer tissues from 189 patients with breast cancer were detected by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). And the objective response rate (ORR) and pathological complete rate (pCR) were analyzed.
 Results: The HER2 protein expression in 46 patients (24.3%) and Topo IIα protein expression in 55 patients (29.1%) was 3+ by IHC or they were 49 (25.9%) and 94 (49.0%) by FISH, respectively. The ORR and pCR in HER2 negative or positive patients were 47.4% and 20.3% or 32.7% and 16.3%, respectively, with significant differences (All P<0.05). The ORR and pCR in Topo IIα positive or negative patients were 69.1% and 36.0% or 28.4% and 2.2%, respectively, with significant differences (All P<0.05).
 Conclusion: FISH and IHC were consistent in the determination of HER2 expression whereas they were inconsistent in the determination of Topo IIα expression. The amplification of Topo IIα can effectively improve the effect of the adjuvant treatment effect of the anthracyclines.
Anthracyclines ; pharmacology ; therapeutic use ; Antibiotics, Antineoplastic ; Breast Neoplasms ; chemistry ; genetics ; therapy ; DNA Topoisomerases, Type II ; physiology ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Neoadjuvant Therapy ; Receptor, ErbB-2 ; physiology ; Treatment Outcome

BACKGROUND/AIMS: Among diffuse large B cell lymphoma (DLBCL) patients, determining the appropriate dose and chemotherapy schedule to balance toxicity and efficacy is harder in elderly than in younger patients. Moreover, there are no currently available clinical factors that consistently identify patients who are unfit to receive chemotherapy. Therefore, the clinical characteristics and outcomes of elderly patients with DLBCL and the causes of treatment-related death were investigated in this study. METHODS: The clinical characteristics and outcomes of 44 elderly (> or = 70 years of age) patients diagnosed with DLBCL between January 2005 and June 2013 were evaluated. Variable clinical data along with the response rate, overall survival (OS), and causes of treatment-related death or treatment interruption were investigated. RESULTS: The median OS was 18.6 months, and 19 patients completed curative treatment. The mean average relative dose intensity of adriamycin in patients who completed chemotherapy was 0.617, and of these patients, 16 achieved complete remission. Chemotherapy incompletion, infectious complications, ex tranoda l involvement, high lactate dehydrogenase, poor performance status, and low albumin level at diagnosis were related to a shorter OS. However, multivariate analysis revealed that only infections and chemotherapy incompletion were significantly related to poor prognosis. The most common cause of treatment-related death was infection, and patients who had experienced infectious complications tended to have lower albumin levels than those of patients without such complications. CONCLUSIONS: In the treatment of elderly lymphoma patients, the dose intensity of adriamycin is not as important as it is in young patients. However, in elderly patients, infections are particularly dangerous, especially in patients with low albumin levels.
Age Factors ; Aged ; Aged, 80 and over ; Antibiotics, Antineoplastic/*administration & dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Chi-Square Distribution ; Communicable Diseases/blood/diagnosis/mortality ; Disease Progression ; Doxorubicin/*administration & dosage/adverse effects ; Female ; Geriatric Assessment ; Humans ; Kaplan-Meier Estimate ; Lymphoma, Large B-Cell, Diffuse/blood/diagnosis/*drug therapy/mortality ; Male ; Multivariate Analysis ; Proportional Hazards Models ; Remission Induction ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Serum Albumin/analysis ; Time Factors ; Treatment Outcome

OBJECTIVETo assess the efficacy of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes.

METHODSClinical data of 48 patients diagnosed and treated for mTNBC between 2004 and 2012 at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) were retrospectively analyzed. All patients were pretreated with anthracyclines and at least one taxane in neo-adjuvant, adjuvant or chemotherapy for mTNBC and patients should be having at least one measurable metastatic lesion. Totally, 48 patients were included in this study, of which 21 cases received first-line chemotherapy and 27 cases received second-line chemotherapy. Based on the regimen they received, 22 patients were treated with NVB plus platinum (NP), and 26 patients with NVB plus capecitabine (NX).

RESULTSAfter 70 months follow-up, in the total group of patients, the objective response rate was 20.8%, clinical benefit rate was 43.8%, median progression free survival (PFS) was 4.4 months and median overall survival (OS) was 15.5 months. In addition, the ORR was significantly better in the NP arm versus NX arm (33.8% vs.7.7%, P=0.029) as well as PFS was statistically improved in the NP arm than NX arm (5.3 m vs. 3.0 m, P=0.023). Similar trend was observed in the OS, although the difference was not statistically significant (27.7 m vs. 14.8 m, P=0.077). In all, the most frequently reported adverse events were G1/2 gastrointestinal toxicity (68.8%) and neutropenia (62.5%) . No significant difference was observed between the NP arm and NX arm (P>0.05). The percentage of patients who delayed chemotherapy administration in the NP arm and NX arm was 9.1% (n=2), and 3.8% (n=1), respectively.

CONCLUSIONSNVB-based combination chemotherapy demonstrates moderate efficacy in mTNBC patients pretreated with anthracyclines and one taxane with manageable toxicity. NP regimen shows potential superiority over NX regimen, and should be further verified in randomized phase III clinical trial in larger cohort.

Anthracyclines ; therapeutic use ; Antibiotics, Antineoplastic ; adverse effects ; therapeutic use ; Antineoplastic Agents, Phytogenic ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bridged-Ring Compounds ; therapeutic use ; Capecitabine ; administration & dosage ; Cisplatin ; administration & dosage ; Disease-Free Survival ; Humans ; Neutropenia ; chemically induced ; Retrospective Studies ; Taxoids ; therapeutic use ; Triple Negative Breast Neoplasms ; drug therapy ; pathology ; Vinblastine ; adverse effects ; analogs & derivatives ; therapeutic use

OBJECTIVETo evaluate the efficacy and safety of cisplatin and capecitabine combination (XP) therapy for patients with metastatic triple negative breast cancer (TNBC) progressing after anthracycline and taxane treatment.

METHODSTwenty-nine metastatic TNBC patients were prospectively enrolled to receive capecitabine (1, 000 mg/m(2) twice daily on days 1-14) and cisplatin (75 mg/m(2) on day 1) , repeated every 3 weeks.

RESULTSWith a median of 6 cycles of XP, all 29 patients were evaluable for response, including 18 PR (62.1%), 6 SD (20.7%), 5 PD (17.2%) and no CR. The response rate was 62.1%. Patients with earlier stage at diagnosis (stage I to IIIA), longer post-operative disease free survival (>2 years) and less metastatic sites (≤ 3) obtained significantly higher response rate than patients with later stage at diagnosis (stage IIIB to IV), shorter post-operative disease free survival (≤ 2 years) and more metastatic sites (>3). The leading side effects were grade 1/2 gastrointestinal and hematological toxicities. Grade 3/4 toxicities included neutropenia (34.5%), leukocytopenia (31.0%), anemia (6.9%), thrombocytopenia (3.4%), nausea/vomiting (20.7%), stomatitis (3.4%), and hand-foot syndrome (3.4%).

CONCLUSIONCisplatin and capecitabine combination therapy is an active and well-tolerated doublet treatment in metastatic TNBC patients progressing after anthracycline and taxane treatments.

Anthracyclines ; administration & dosage ; Antibiotics, Antineoplastic ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bridged-Ring Compounds ; administration & dosage ; Capecitabine ; administration & dosage ; adverse effects ; Cisplatin ; administration & dosage ; adverse effects ; Disease-Free Survival ; Female ; Hand-Foot Syndrome ; Humans ; Leukopenia ; chemically induced ; Neutropenia ; chemically induced ; Prospective Studies ; Taxoids ; administration & dosage ; Treatment Outcome ; Triple Negative Breast Neoplasms ; drug therapy ; pathology