Efficacy and survival outcomes of dose-dense carboplatin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer / 中华肿瘤杂志

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.

A Phase II Study to Evaluate the Safety and Efficacy of Pegteograstim in Korean Breast Cancer Patients Receiving Dose-Dense Doxorubicin/Cyclophosphamide / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Dose-dense chemotherapy (DD-CT) is a preferred (neo)adjuvant regimen in early breast cancer (BC). Although the results of reported randomized trials are conflicting, a recent meta-analysis showed improved overall and disease-free survival with DD-CT compared to conventional schedules. However, no DD-CT safety data for Korean BC patients are available. This phase II study was conducted to evaluate the safety and efficacy of pegteograstim in Korean BC patients receiving DD-CT. MATERIALS AND METHODS: Patients with operable (stage I-III), histologically confirmed BC received four cycles of intravenous doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 every 2 weeks as neoadjuvant or adjuvant therapy. Pegteograstim (6.0 mg) was administered subcutaneously on day 2 of each cycle. The primary endpoint was the incidence of febrile neutropenia (FN). The secondary endpoints were safety and tolerability. RESULTS: Of 63 patients, one (1.6%) developed FN during all cycles of DD-CT. Dose delay was observed in four patients (6.3%) and dose reduction in two (3.2%) during DD-CT. Frequent adverse events (AEs) were nausea, alopecia, generalized muscle weakness, myalgia, mucositis, anorexia, dyspepsia, and diarrhea; most AEs were related to chemotherapy. Grade 3-4 AEs were reported in five of 63 patients (7.9%), and all grade 3 and 4 AEs were related to chemotherapy. Adverse drug reactions possibly linked to pegteograstim were abdominal pain, bone pain, myalgia, generalized muscle weakness, and headache in five of 63 patients (7.9%). CONCLUSION: Dose-dense AC (doxorubicin/cyclophosphamide) chemotherapywith pegteograstim support is a tolerable and safe regimen in Korean early BC patients.

Feasibility and toxicity of EC-T dose-dense adjuvant chemotherapy: A real world study in Chinese early-stage breast cancer patients with high recurrence risk / 中华肿瘤杂志

Objective@#We aimed to examine the feasibility and toxicity of EC-T dose-dense regimen and to demonstrate the suitable dose of epirubicin in a Chinese early-stage breast cancer population with high recurrence risk.@*Methods@#370 patients with early-stage breast cancer at high risk of recurrence were treated with EC-T dose-dense adjuvant chemotherapy and prophylactic administration of recombinant human granulocyte stimulating factor (G-CSF). The incidence of delayed chemotherapy, drug reduction and adverse reactions were retrospectively analyzed.@*Results@#370 patients completed the planned eight cycles of chemotherapy, 50 patients experienced chemotherapy delay, and 90 had chemotherapy dose reductions. Overall, 61.1% of the patients experienced grade 3 or 4 hematology toxicities, 4.1% of the patients experienced grade 3 gastrointestinal toxicity, 16.3% experienced grade 3 or 4 liver malfunction, and 1.9% experienced grade 3 alopecia. In the multivariate analysis, pretreatment epirubicin levels were associated with comprehensive and hematology toxicity risk (OR=1.268, P=0.046; OR=1.244, P=0.036). With G-CSF support, the probability of grade 3-4 dose limiting toxicity, i. e. neutropenia, abnormal liver function, and gastrointestinal adverse effects did not increase as the epirubicin dose level increased(P>0.05). However, there were no statistically significant associations between epirubicin grade and treatment delay (P=0.814) or dose reduction (P=0.282).@*Conclusions@#EC-T dose-dense chemotherapy shows tolerable toxicity. High dose level is not a limiting factor for this regimen. With G-CSF support, epirubicin 85-90 mg/m2 is appropriate tolerance dose for Chinese early breast cancer patients with high recurrence risk.

Comparison of the efficacy and adverse reactions between dose-dense biweekly EC-T regimen and three-weekly TEC regimen in adjuvant chemotherapy for high risk breast cancer / 肿瘤研究与临床

Objective To compare the adverse reactions and efficacy of dose-dense biweekly EC-T regimen with three-weekly TEC regimen in adjuvant chemotherapy for high risk breast cancer patients. Methods Fifty-one patients with high-risk breast cancer were divided into two groups according to random number table method. 27 cases in EC-T group: epirubicin 90 mg/m2, d1, cyclophosphamide 600 mg/m2, d1, every 2 weeks for 4 cycles followed by paclitaxel 175 mg/m2, d1, every 2 weeks for 4 cycles; 24 cases in TEC group: docetaxel 75 mg/m2, d1, epirubicin 75 mg/m2, d1, and cyclophosphamide 500 mg/m2, d1, every 3 weeks. All the patients in both groups received prophylactic granulocyte-colony stimulating factor 5 μg/(kg·d) from d3 of chemotherapy according to treatment protocol. The adverse reactions, disease-free survival (DFS) and overall survival (OS) were compared between the two groups using χ2 test. Results After a median follow-up of 31 months, the median DFS in the two groups were 28 months and 26 months, the 2-year DFS rates were 85.2 % and 79.2 %, and the 2-year OS rates were 100.0 % and 95.8 %. The EC-T group had higher median DFS, 2-year DFS and 2-year OS than the TEC group, but the differences were not statistically significant (all P> 0.05). The EC-T group had lower incidence of grade 3-4 leukopenia and neutropenia, grade 2-3 diarrhea than the TEC group, and no febrile neutropenia was observed in the EC-T group, the differences were statistically significant (all P 0.05). Conclusion EC-T dose-dense biweekly regimen is well tolerated in adjuvant chemotherapy for high risk breast cancer patients with a trend to improve the DFS and OS when compared with the TEC regimen.

Effect of the dose-dense temozolomide on glioblastoma:A network meta-analysis / 实用医学杂志

Objective To analyze the intervention effect of the dose-dense schemes of temozolomide on the newly diagnosed glioblastoma compared with the standard schemes. Methods The Pubmed,Cochrane,Em-base,CNKI,CBM,Wanfang,VIP databases were used for the retrievals on the intervention effect.The quality of included papers was assessed to extract network meta-analysis data with using the statistical software Stata 13.0. Results The treatment plans were ranked according to the intervention effect from the best to the worst as follows:the dose-dense,the early,the metronomic,the standard,the RT and post-RT adjuvant temozolomide. The most common adverse effects in hematotoxicity were neutropenia,leucopenia,lymphopenia,thrombocytopenia and ane-mia. Between the different temozolomide therapeutic regimens,there was no significant difference. Conclusion The intervention effect of the dose-dense schemes with temozolomide is better than the standard therapy. It also revealed that,the hematoxicity in the different temozolomide schemes is not significantly different.

Long-term recurrence-free survival of a patient with advanced pure primary ovarian squamous cell carcinoma treated with dose-dense paclitaxel combined with carboplatin

We describe an extremely rare case of advanced pure primary ovarian squamous cell carcinoma (SCC), treated by adjuvant chemotherapy with dose-dense paclitaxel combined with carboplatin (dd-TC) plus the combination chemotherapy with irinotecan and cisplatin (CPT-P), with long-term recurrence-free survival. A 71-year-old woman complaining of lower abdominal pain was referred to our hospital and a 7-cm-diameter solid tumor was identified. She was diagnosed with a left ovarian tumor that was highly suspicious for malignancy based on ultrasonography, magnetic resonance imaging, and contrast-enhanced computed tomography. Bilateral salpingo-oophorectomy, low-anterior colon resection, and colostomy were performed. Intra- and post-operative histopathological diagnosis revealed International Federation of Gynecology and Obstetrics stage IIIc well-differentiated pure ovarian SCC. As adjuvant chemotherapy, 2 courses of dd-TC were administered, followed by 3 courses of CPT-P; the patient then underwent 4 additional courses of dd-TC. Both regimens were effective and there has been no recurrence or metastasis thus far in the 5 years since the operation.

Clinic study of dose-dense cisplatin and 5-fluorouracil in patients with distant metastatic nasopharyngeal carcinoma / 国际肿瘤学杂志

Objective To investigate the efficacy and tolerability of dose-dense chemotherapy with cisplatin plus 5-fluorouracil( PF regimen)in distant metastatic nasopharyngeal carcinoma( NPC)patients. Methods From April 1,2008 to April 30,2014,168 patients were assigned to traditional group(n = 83) and dose-dense group(n = 85)using digital random table in 1 : 1 ratio. All patients received PF regimen,and once every 28 days in traditional group and once every 14 days in dose-dense group. The primary endpoint was progression-free survival(PFS)and the secondary endpoint was overall survival(OS),toxicity and response rate. Results The median PFS,median OS,1,2,3-year survival rate,complete response rate and objective response rate were significantly improved in dose-dense group which were 13. 3 months,20. 2 months,80. 2% , 36. 0% ,16. 1% ,16. 5% ,84. 7% ,and those in control group were 10. 0 months,16. 1 months,59. 6% , 10. 1% ,0,3. 6% ,54. 2% respectively(χ2 = 24. 47,P = 0. 000;χ2 = 16. 65,P = 0. 000;χ2 = 8. 41,P =0. 004;χ2 = 16. 96,P = 0. 000;χ2 = 14. 91,P = 0. 000;χ2 = 7. 63,P = 0. 006;χ2 = 18. 47,P = 0. 000). The rates of grade 3-4 adverse events in dose-dense and traditional group were 38. 8% and 6. 0%(χ2 = 25. 81, P = 0. 000). Conclusion Dose-dense chemotherapy of PF is more efficient and acceptable toxic than the tra-ditional one. It can be a new treatment option for patients with distant metastases of NPC.

Major clinical research advances in gynecologic cancer in 2013 / 부인종양

In 2013, 10 topics were selected for major clinical research advances in gynecologic oncology; these included three topics regarding cervical cancer, three regarding ovarian cancer, two regarding endometrial cancer, and one each regarding breast cancer and radiation oncology. For cervical cancer, bevacizumab was first demonstrated to exhibit outstanding clinical efficacy in a recurrent, metastatic setting. Regarding cervical cancer screening, visual inspections with acetic acid in low-resource settings, p16/Ki-67 double staining, and the follow-up results of four randomized controlled trials of human papillomavirus-based screening methods were reviewed. Laparoscopic para-aortic lymphadenectomy before chemoradiation for locally advanced cervical cancer was the final topic for cervical cancer. Regarding front-line ovarian cancer therapies, dose-dense paclitaxel and carboplatin, intraperitoneal chemotherapy, and other targeted agents administered according to combination or maintenance schedules were discussed. Regarding recurrent ovarian cancer treatment, cediranib, olaparib, and farletuzumab were discussed for platinum-sensitive disease. The final overall survival data associated with a combination of bevacizumab and chemotherapy for platinum-resistant disease were briefly summarized. For endometrial cancer, the potential clinical efficacy of metformin, an antidiabetic drug, in obese patients was followed by integrated genomic analyses from the Cancer Genome Atlas Research Network. For breast cancer, three remarkable advances were reviewed: the long-term effects of continued adjuvant tamoxifen for 10 years, the effects of 2-year versus 1-year adjuvant trastuzumab for human epidermal growth factor receptor 2-positive disease, and the approval of pertuzumab in a neoadjuvant setting with a pathologic complete response as the surrogate endpoint. Finally, the recent large studies of intensity-modulated radiotherapy for gynecologic cancer were briefly summarized.

Advanced ovarian cancer: what should be the standard of care? / 부인종양

The standard treatment of advanced ovarian cancer is rapidly changing. As we begin to understand that epithelial ovarian cancer is a heterogeneous disease, our treatment strategies are evolving to include novel biologic drugs that specifically exploit altered pathways. Surgery remains an essential component in the treatment of ovarian cancer; however, the importance of surgical specialization and defining "optimal cytoreduction" as no visible residual disease has been further validated. Ongoing studies are defining the role of neoadjuvant chemotherapy in the upfront treatment of advanced ovarian cancer. In addition, clinical trials are evaluating intraperitoneal, dose dense, antiangiogenic drugs as well as targeted maintenance therapies which will establish new standards of care in the near future.