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 evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Humans ; Neoadjuvant Therapy/adverse effects* ; Paclitaxel/therapeutic use* ; Treatment Outcome ; Triple Negative Breast Neoplasms/pathology*

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 μmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 μmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 μmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 μmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.
Breast Neoplasms/enzymology* ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Female ; Humans ; MCF-7 Cells ; N-Terminal Acetyltransferases/metabolism* ; Organoplatinum Compounds/pharmacology* ; Oxaliplatin/pharmacology* ; X-ray Repair Cross Complementing Protein 1

Colorectal cancer is the second most common malignant tumor in China. The FOLFOXIRI regimen, which combines 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan, is a high-intensity and highly effective chemotherapy regimen. However, the original regimen is poorly tolerated in Chinese patients. In order to promote the standardized and rational application of FOLFOXIRI regimen by clinicians in China, "
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Camptothecin/therapeutic use* ; China ; Colorectal Neoplasms/drug therapy* ; Consensus ; Fluorouracil/therapeutic use* ; Humans ; Irinotecan/therapeutic use* ; Leucovorin/therapeutic use* ; Organoplatinum Compounds/therapeutic use* ; Oxaliplatin ; Treatment Outcome

OBJECTIVE: To observe the early efficacy and toxicity of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: From May 2017 to July 2019, fifteen patients with mCRPC treated in Peking University First Hospital were collected. The median age was 70 years (43-77 years), and the pathological types were all adenocarcinoma, which was confirmed as distant metastasis by imaging examination. They were given the chemotherapy of docetaxel combined with carboplatin. The specific method was as follows: each cycle was 28 days. Androgen deprivation therapy was administered routinely throughout the treatment period. Blood routine, liver and kidney function, blood clotting function and prostate-specific antigen (PSA) tests were performed before each cycle. Docetaxel was administered intravenously on the first day of each cycle at a dose of 75 mg/m², and carboplatin was administered intravenously on the second day at the dose calculated by Calvert formula. The main outcome measures including PSA decline range, pain remission rate and occurrence of adverse reactions were observed and analyzed. RESULTS: Among the 15 patients, 12 had completed at least 4 cycles of chemotherapy and had short-term efficacy evaluation. PSA decline range > 50% was observed in 8 patients (66.7%). Among the 9 patients with bone pain, remarkable pain relief was observed in 4 patients (44.4%). Among the 4 patients with measurable metastatic lesions, 2 achieved partial response, 1 was evaluated as stable disease, and 1 was evaluated as progressive disease. The main adverse reactions of chemotherapy included bone marrow suppression, gastrointestinal reactions, fatigue and neurological disorders, and most of them were within the tolerable range. CONCLUSION This report is a case series study of docetaxel combined with carboplatin in the treatment of mCRPC reported in China and the conclusions are representative. The chemotherapy of docetaxel combined with carboplatin has positive short-term efficacy and high safety in patients with mCRPC, which is worthy of further promotion and exploration in clinical practice.
Aged ; Androgen Antagonists/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Docetaxel/therapeutic use* ; Humans ; Male ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Treatment Outcome

OBJECTIVE: To compare the efficacy and toxicity of dose-dense weekly paclitaxel and 3-weekly carboplatin (ddPC) as neoadjuvant chemotherapy (NAC) with the standard 3-weekly regimen.METHODS: A retrospective study of patients diagnosed with stage IIIc and IV ovarian cancer who received at least one cycle of NAC followed by interval debulking surgery between August 2015 and January 2018 was conducted. Patient characteristics, clinical and pathological response to NAC, surgical and survival outcome, and adverse event were compared.RESULTS: A total of 23 patients in the ddPC group and 50 patients in the standard group received a median of 3 cycles of NAC. Rate of grade ≥3 neutropenia was significantly higher in the ddPC group than the standard (82.6% vs. 22.0%, p<0.001). Patients in the ddPC group underwent dose-reduction more frequently (34.8% vs. 4.00%, p=0.001). Normalization of cancer antigen-125 post-NAC occurred more frequently in the ddPC group (73.9% vs. 46.0%, p=0.030). No residual disease rate (43.5% vs. 60.0%, p=0.188) and chemotherapy response score of 3 (34.8% vs. 26.0%, p=0.441) were not statistically different between two groups. There was no statistical difference in progression free survival (PFS) at 2 years (36.3% vs. 28.4%, p=0.454). Cox proportional hazard model showed that ddPC was not a significant determinant of PFS (p=0.816).CONCLUSION: There was no difference between both regimens in terms of NAC response and survival outcomes. However, ddPC group showed higher hematologic toxicity requiring dose reduction.
Carboplatin ; Disease-Free Survival ; Drug Therapy ; Humans ; Neoadjuvant Therapy ; Neutropenia ; Ovarian Neoplasms ; Paclitaxel ; Proportional Hazards Models ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To evaluate the effectiveness and safety of the combination of pegylated liposomal doxorubicin with carboplatin (CD) compared with those of carboplatin and paclitaxel (CP) for platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer in a real-world setting in Korea.METHODS: We enrolled relevant patients from 9 institutions. All patients received CD or CP as the second- or third-line chemotherapy in routine clinical practice during 2013–2018. The primary endpoints were progression-free survival (PFS) and toxicity. The secondary endpoint included the objective response rate (ORR).RESULTS: Overall, 432 patients (224 and 208 in the CD and CP groups, respectively) were included. With a median follow-up of 18.9 months, the median PFS was not different between the groups (12.7 vs. 13.6 months; hazard ratio, 1.161; 95% confidence interval, 0.923–1.460; p=0.202). The ORR was 74.6% and 80.1% in the CD and CP group, respectively (p=0.556). Age and surgery at relapse were independent prognostic factors. More patients in the CD group significantly experienced a grade 3 to 4 hematologic toxicity and hand-foot syndrome (13.8% vs. 6.3%), whereas grade 2 or more alopecia (6.2% vs. 36.1%), peripheral neuropathy (4.4% vs. 11.4%), and allergic/hypersensitivity reaction (0.4% vs. 8.5%) developed more often in the CP group.CONCLUSIONS: The safety and effectiveness of chemotherapy with CD in a real-world setting were consistent with the results from a randomized controlled study. The different toxicity profiles between the 2 chemotherapy (CD and CP) regimens should be considered in the clinical practice.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03562533
Alopecia ; Carboplatin ; Cohort Studies ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Follow-Up Studies ; Hand-Foot Syndrome ; Humans ; Korea ; Ovarian Neoplasms ; Paclitaxel ; Peripheral Nervous System Diseases ; Platinum ; Prognosis ; Recurrence ; Retrospective Studies

carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m2, n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis.RESULTS: Enrollment was slow, accrual was closed when 7+ years had passed. With a median follow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19–0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCA/non-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11–1.18; p=0.091).CONCLUSIONS: Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.]]>
Arm ; Asian Continental Ancestry Group ; Bias (Epidemiology) ; Carboplatin ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Follow-Up Studies ; Humans ; Maintenance Chemotherapy ; Ovarian Neoplasms ; Prognosis ; Quality of Life ; Recombination, Genetic ; Sample Size

OBJECTIVE: To compare response rate and survivals of locally advanced stage cervical cancer patients who had standard concurrent chemoradiation therapy (CCRT) alone to those who had adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18–70 years who had International Federation of Gynecology and Obstetrics stage IIB–IVA without para-aortic lymph node enlargement, Eastern Cooperative Oncology Group scores 0–2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or by ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: Data analysis of 259 patients showed no significant difference in complete responses at 4 months after treatment between arm A (n=129) and arm B (n=130): 94.1% vs. 87.0% (p=0.154) respectively. With the median follow-up of 27.4 months, 15.5% of patients in arm A and 10.8% in arm B experienced recurrences (p=0.123). There were no significant differences of overall or loco-regional failure. However, systemic recurrences were significantly lower in arm B than arm A: 5.4% vs. 10.1% (p=0.029). The 3-year progression-free survival (PFS) and 3-year overall survival (OS) of the patients in both arms were not significantly different. The hazard ratio of PFS and OS of arm B compared to arm A were 1.26 (95% CI=0.82–1.96; p=0.293) and 1.42 (95% CI=0.81–2.49; p=0.221) respectively. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response rate and survival compared to CCRT alone. Only significant decrease of systemic recurrences with ACT was observed, but not overall or loco-regional failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036164 Thai Clinical Trials Registry Identifier: TCTR 20140106001
Arm ; Asian Continental Ancestry Group ; Carboplatin ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Cisplatin ; Disease-Free Survival ; Follow-Up Studies ; Gynecology ; Humans ; Lymph Nodes ; Obstetrics ; Paclitaxel ; Recurrence ; Statistics as Topic ; Uterine Cervical Neoplasms