BRCA1和EGFR是多西他赛联合顺铂方案治疗的三阴性乳腺癌预后的重要标志物(英文)

Objective:The triple negative (TN) metastatic breast cancer (MBC) patients are known to have worse prognosis,shorter progressive free survival (PFS),and overall survival (OS),that mandates using aggressive chemotherapy regimens.This phase II study aimed at investigating the efficacy and safety of using cisplatin and docetaxel in patients with triple negative metastatic breast cancer,and the possibility of using breast cancer susceptibility gene1 (BRCA1) expression as a predictive marker of chemotherapy response,and epidermal growth factor receptor (EGFR) as prognostic marker.Method:Between January 2006 and March 2009,40 eligible patients with TN MBC were included in the study.We examined BRCA1 expression and EGFR protein in their specimens using immunohistochemistry.The patients were treated with cisplatin 75 mg/m2 and docetaxel 75 mg/m2 every 3 weeks,TN measurable MBC patients previously treated with anthracycline in their adjuvant or neo adjuvant settings were included in the study.Results:The median age of the treated patients was 43.5 years.Nearly half of the patients had an ECOG performance status of 0 or 1,and about third of them had one metastatic site.These metastatic sites were predominantly visceral in 80% of the patients.Fifty-five percent of TNMBC stained positive for BRCA1 and sixty-five percent for EGFR.Positivity for both markers was significantly associated with grade III tumors (P=0.004),OS,and PFS (P=0.001 and 0.009) respectively.Overall,the regimen was well tolerated as GIII vomiting and neurological side effects were observed in 20% of the patients.Other toxicities were generally mild and medically manageable;with no treatment mortality was recorded.The overall disease control rate (ODCR) was 60%;the median PFS was 8 months,with a median overall OS of 17.5 months;while the median OS among responders was 23 months (95% CI 21.35 to 25.32).The patients with negative EGFR had a significantly better OR,PFS,and OS than EGFR positive cases.There was no significant difference concerning OR,PFS,and OS,between positive and negative BRCA1 cases,which could be attributed to the better efficacy of cisplatin in the positive BRCA1 cases.Conclusion:This chemotherapy regimen is effective with tolerable toxicity profile,our results point out the importance of BRCA1 expression as predictive marker of chemotherapy response,and EGFR as prognostic marker,which could identify a certain group of patients with more aggressive disease who might benefit from using anti EGFR targeted therapy plus cisplatin.

未化疗的广泛期小细胞肺癌患者吉西他滨联合顺铂诱导化疗后口服依托泊苷维持治疗疗效评估(英文)

Objective:The aim of our study was to evaluate the response and tolerability to treatment when using gemcitabine-cisplatin combination(GC),followed by maintenance therapy of oral etoposide for non-progressive patients in trial to improve progression free survival and overall survival.Methods:Thirty nine patients with extensive small cell lung cancer(SCLC) and ECOG ≤ 2 received 4 cycles of chemotherapy consisting of gemcitabine 1000 mg/m2(day 1 and 8) cisplating 75 mg/m2(day 1) every three weeks.Twenty seven non-progressive patients after 4 cycles of chemotherapy were randomized either to receive oral etoposide 50 mg/m2 for consecutive 15 days every 3 weeks vs no therapy for three months or progression.Results:Thirty nine eligible patients treated with GC,27 non progressive patients were subsequently randomized to oral etoposide or observation.Median follow-up was 18 months.The overall response rate to GC was 59% and toxicity to oral etoposide was mild.There was improvement in median progression-free survival(PFS) favoring the maintenance arm of 10.5 months vs 7 months(P < 0.05).Median overall survival(OS) had improved towards the maintenance arm(13 vs 11.5 months).One year survival(60% vs 24%),18 months survival(20% vs 5%) favoring the maintenance.Multivariate analysis revealed that age,performance status,maintenance therapy,and response to treatment were independent prognostic factors for OS.Age,maintenance therapy,and response to treatment were highly significant factors for PFS.Conclusion:Gemcitabine-cisplatin is an effective and tolerable regiment for extensive disease of SCLC.The addition of 3 months of oral etoposide in non progressing patients was associated with a significant improvement of PFS and longer OS.

进展期肝细胞癌患者的卡培他滨加顺铂的联合治疗(英文)

Objective:Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third leading cause of cancer related death globally.Parentral treatment of Egyptian patients of bilharziasis contributed to the high incidence of viral hepatitis,and subsequently liver cirrhosis and HCC.Capecitabine plus cisplatin protocol was evaluated regarding the efficacy and safety in patients with advanced HCC as first line chemotherapy.Methods:One hundred patients with advanced HCC were randomized to receive either capecitabine (1000 mg/m 2) twice daily for fourteen days plus intravenous cisplatin (60 mg/m 2) on day one to be repeated every three weeks with a maximum of six cycles or placebo (phase III trial).Results:Baseline characteristics were comparable in both groups.According to Barcelona Clinic Liver Cancer Staging System,stage C was the most predominant (82% vs.75%) in both groups.Median OS was 12 months versus 10 months in favor of the treated group (P value < 0.05).Median TTP was significantly higher in the chemotherapy group (7 months vs.4.5 months) as well as disease control rate (40% vs.29%),no patient had achieved complete response.Grade 3 toxicity was more pronounced in the treatment group,as regards vomiting and diarrhea (10% vs.2%),neurotoxicity (6% vs.2%),elevation of aminotransferase and bilirubin (9.8% vs.4.9%),hand and foot syndrome reaction was recorded only in chemotherapy group.Conclusion:Capecitabine plus cisplatin regimen showed modest antitumor activity with tolerable toxicity in patients with advanced HCC.Moreover,because of the significantly prolonged time to progression,we demand further attention to this convenient,outpatient,and economic profile based chemotherapy protocol.

绝经后妇女患早期乳腺癌后阿那曲唑及他莫昔芬治疗所致的有关骨矿物质密度和骨生物标记物Osteocalcin的骨骼事件比较(英文)

Objective:Postmenopausal women with breast cancer are at increased risk of bone loss because of age related estrogen deficiency face which accelerated with the use of aromatase inhibitors(AIs).We aimed to study the effect on bone mineral density(BMD) and bone formation biomarker osteocalcin level in postmenopausal breast cancer patients,for the first three years of adjuvant hormonal treatment of both groups Tamoxifen versus Anastrozol.Methods:One-hundered postmenopausal breast cancers were prospectively randomized to receive either Tamoxifen 20 mg/day(n = 50) or Anastrozole 10 mg(n = 50).Both BMD and osteocalcin were assessed initially before treatment and then at regular intervals for both groups.Results:Use of Tamoxifen was associated with significant annual decrease in osteocalcin(P = 0.001),whereas Anastrozole group had gradual increase of the annual levels(P < 0.01).BMD decreased significantly in Anastrozole versus Tamoxifen groups(2.6% vs.0.4%,P < 0.001).Osteoporosis T <-2.5 was reported significantly higher in Anastrozole group(P < 0.01).Women with initial osteopenia in Anastrozole group showed significant decrease in BMD(P < 0.05).The addition of bisphosphonate for patients with early osteoporosis markedly improved both osteocalcin level and BMD.Conclusion:Tamoxifen preserves BMD in postmenopausal breast cancer patients,whereas Anastrozole accelerates age associated fall in BMD especially in the first year of therapy,moreover,the addition of bisphosphonate can help to decrease the skeletal related events associated with treatment to ensure better quality of life with treatment.