长春地辛、吡柔比星、环磷酰胺、地塞米松联合治疗非霍奇金淋巴瘤的疗效观察

目的观察应用长春地辛(VDS)、吡柔比星(THP)、环磷酰胺(CTX)、地塞米松(DXM)联合治疗非霍奇金淋巴瘤的疗效及不良反应。方法患者予以VDS 2.5 mg.m-2,d1,8;THP 25 mg.m-2,d1,8;CTX 0.6 g.m-2,d1,8;DXM 10 mg.d-1,d1-10。28 d重复,2个疗程予以评价。结果总有效率(CR PR)为82.1%,不良反应为血液毒性,经G-CSF治疗可恢复,未见明显的外周神经毒性。结论VDS、THP、CTX和DXM联合治疗淋巴瘤安全有效。     

Phase II study of Fenretinide (N-[4-Hydroxyphenyl]retinamide) in advanced breast cancer and melanoma

Summary Retinoids, the natural and synthetic analogs of vitamin A, are growth-inhibiting and differentiation-inducing agents and show clinical promise as chemopreventive and antineoplastic agents. Fenretinide, a new synthetic retinoid, has antitumor activity in certain in vitro and in vivo model systems and was relatively nontoxic in phase I trials. Based on these data, we designed a phase II study of Fenretinide involving 31 patients with advanced breast cancer [15] and melanoma [16], two cancers shown to be responsive to this agent in preclinical models. Fenretinide was inactive in patients with advanced disease. Toxicity was mild, and reversible. Mucocutaneous side effects occurred in 16 (52%) patients. Nyctalopia developed in three patients one of whom developed decreased B-wave amplitude of the scotopic electroretinogram. The minimal toxicity and significant activity in preclinical studies make this an attractive agent for future breast cancer chemoprevention studies.     

Trilostane in advanced breast cancer

Antiestrogens, principally tamoxifen, and aromatase inhibitors have been used as the first- and second-line therapy in patients with advanced postmenopausal breast cancer for many years. However, some patients acquire resistance to these treatments and, at present, further endocrine treatment is achieved by merely substituting the current medication with a different antiestrogen or aromatase inhibitor. Trilostane offers an alternative endocrine treatment due to its unique mode of action. It is an allosteric modulator of the estrogen receptor and targets both the estrogen- and growth factor-dependent pathways through which estradiol stimulates cell proliferation. In clinical trials, trilostane has been shown to be an effective treatment for breast cancer in patients who have relapsed after receiving treatment with one or more forms of endocrine therapy. Ongoing and future clinical trials are examining the potential for the use of trilostane in premenopausal breast cancer, as well as in other malignancies such as prostate cancer.     

Methyl-glyoxal bis guanyl hydrazone (methyl-GAG,MGBG) in advanced breast cancer

Summary The Southwest Oncology Group has evaluated methyl-GAG on a weekly schedule among patients with metastatic breast cancer. Among 72 fully and partial evaluable patients, one complete and four partial responses were seen. Toxicity was similar to other trials with this compound except for thrombocytopenia which was more frequent and severe and probably related to tumor infiltrating marrow. In addition, one patient experienced recall dermatitis following methyl-GAG. This toxicity has not been previously reported with this compound. Methyl-GAG has minimal activity at this dose and schedule among heavily pretreated patients with breast cancer. Address for reprints: Southwest Oncology Group (7921), 4450 Medical Drive, San Antonio, TX 78229, U.S.A.     

Phase II trial with oral idarubicin in advanced breast cancer

Summary Idarubicin, a new analogue of daunorubicin, was administered to 27 patients with advanced breast cancer in a phase II trial. The drug was given orally at a dose of 30–35 mg/m² every 3 weeks. Twenty-two patients were evaluable for response. All evaluable patients were previously treated with one or more chemotherapeutic regimens, including an anthracycline in more than 50% of the cases. Partial remissions were obtained in 5 patients, for a response rate of 23%. The median duration of response was 191 days. Mild nausea and vomiting were common. Diarrhea, which occurred in less than 50% of the patients, was usually short-lived. Alopecia was generally minimal. Myelosuppression was the dose-limiting toxic effect. Leukopenia was frequently seen, with full recovery by day 28 in 81 % of the courses. Thrombocytopenia was less common than leukopenia. Four cases of grade 1 acute cardiac toxicity were recorded. This study suggests that idarubicin can induce regressions in advanced carcinoma of the breast, and justifies further studies in combination with other agents.     

Mitoxantrone combined to vincristine,cyclophosphamide and fluorouracil in advanced breast cancer

Summary In our wide experience of treating advanced breast carcinoma with chemotherapy, the combination of doxorubicin (DOX), vincristine (VCR), cyclophosphamide (CPM) and fluorouracil (FU) gave a complete plus partial response rate of over 60%, with 100% alopecia and frequent cardiac toxicity depending on total dose.After the EORTC Clinical Screening Group phase II trial we have conducted an expected difference method comparative phase II trial using the combination DOX, VCR, CPM, FU and the combination of MTX (10mg/m²), VCR, CPM and FU on a population of 50 breast carcinoma patients similar to those taking part in the first study.The reasons for similarity of action will be presented and discussed.     

乳癌根治术后放化疗对乳腺癌中晚期患者T淋巴细胞及生存率的影响

目的探讨乳癌根治术后放化疗对乳腺癌中晚期患者T淋巴细胞及生存率的影响。方法选择本科2010年6月～2011年12月收治的乳腺癌中晚期患者56例,治疗方案为手术＋放疗＋化疗,手术方式为乳癌根治术。术后进行化疗分别于第1、8天给予多西紫杉醇75mg／m2静脉滴注,缓慢滴注时间为3h;术后第1～3天给予顺铂溶于生理盐水250ml静脉滴注,剂量20mg／m2,时间1h,3周为1个周期;三维适形放疗为DT2Gy／次。1次／d,5次／周,观察患者治疗前后相关免疫指标的变化及生存率。结果患者治疗后的CD3、CD4、CD8、CD4／CD8及NK较治疗前均降低,差异有统计学意义（P〈0．05）。乳癌根治术56例,乳癌改良根治术占33．93％（19／56）。术后随访1年局控率达到75．O％（42／56）,1年生存率达到80．36％（45／56）,2年局控率达到21．43％（12／56）,2年生存率达到26．78％（15／56）,临床总有效率为76．78％（43／56）。结论乳腺癌中晚期患者乳癌根治术后放化疗对机体免疫力可造成一定的影响,治疗中应考虑其不良反应,针对性地采取相应治疗方案,以提高临床疗效。     

Advances in chemical pharmacotherapy to manage advanced breast cancer

Introduction: Advanced breast cancer is still incurable. However, patients diagnosed with this fatal disease live longer. The selection of systemic therapy is mainly based on molecular subtype. The aim of management in these patients is to not only improve outcome, but also to maintain quality of life.

Areas covered: In this paper we focus on available treatments and drugs under late development in the three main subtypes of breast cancer: luminal (hormone receptor positive), HER2 positive and triple negative disease. Main advances during the last years have been made in the treatment of HER2 positive breast cancer with the approval of several new targeted agents. Luminal breast cancer is also a field of active clinical research. So far triple negative breast cancer remains the subtype with the worse prognosis, even though new discoveries have been made to better understand the huge heterogeneity of this type of breast cancer.

Expert opinion: Several new treatment options have recently been established in metastatic breast cancer. Side effects are sometimes cumbersome for the patient and are difficult to manage easily. Thus, identification of patients who derive the most benefit is needed. In addition, collaborative efforts should integrate the genotypic fragmentation in the management and future clinical research strategies of metastatic breast cancer patients.     

Elliptinium: Phase II study in advanced measurable breast cancer

Summary Eighteen patients with advanced measurable breast cancer were treated with elliptinium acetate 100 mg/m² × 3 days every 3 weeks. Fourteen of these patients had failed prior chemotherapy. Two patients had an objective tumor response of greater than 4 weeks. Myelosuppression, renal insufficiency and thrombophlebitis were rarely encountered and alopecia was not seen at all. This study demonstrates that elliptinium has minimal activity in recurrent breast cancer with a favorable toxicity profile.     

Sorafenib in locally advanced or metastatic breast cancer

Introduction: Sorafenib is an oral multikinase inhibitor with anti-angiogenic and anti-proliferative activity that is indicated for use in hepatocellular and renal cell carcinomas. Sorafenib is being developed in a number of solid tumors, including breast cancer (BC).

Areas covered: A series of four randomized, double-blind, placebo-controlled Phase IIb screening Trials were developed to Investigate the Efficacy of Sorafenib (TIES) when added to select chemotherapies for patients with HER2-negative advanced BC with a primary endpoint of progression-free survival (PFS). Results have been varied. SOLTI-0701 reported significant PFS benefit for sorafenib plus capecitabine as first- or second-line treatment, and AC01B07 reported a modest but significant PFS benefit when sorafenib was combined with gemcitabine or capecitabine for patients whose disease had progressed during or after bevacizumab. Sorafenib plus first-line paclitaxel did not significantly improve PFS (NU07B1 study), nor did its addition to first-line docetaxel and/or letrozole (FM-B07-01 study). A Phase III trial of sorafenib plus capecitabine has been initiated.

Expert opinion: Phase IIb data indicate a potential role for sorafenib in combination with select chemotherapies for HER2-negative advanced BC, but Phase III confirmatory trials are necessary. The variability in results across studies with sorafenib may be related to the chemotherapy combination and/or patient population.     

First-line combination chemotherapy with mitoxantrone and cyclophosphamide in advanced breast cancer

Summary In this study, 30 evaluable patients with advanced carcinoma of the breast were treated with cyclophosphamide 600 mg/m² i.v. followed one day later with mitoxantrone (Novantrone®; dihydroxyanthracenedione) 16 mg/m² i.v. Drug treatment was repeated every 3–4 weeks, for a maximum of 12 cycles. The overall response rate was 43%; five of 30 patients (16%) attained a complete remission, and eight of 30 (27%) had a partial remission. Median response duration was 12+ months. The greater number of responses was seen in skin and soft tissues. Hematologic toxicity was limiting with 75% of patients experiencing substantial-severe leukopenia. Clinically evident heart failure developed in one patient; in three other patients there was minor-moderate alteration of cardiac function during mitoxantrone-cyclophosphamide therapy. Based on these data, it is believed that this regimen may provide significant long-lasting palliation in patients with advanced breast cancer.     

大剂量顺铂治疗晚期乳腺癌(附36例报告)

目的：探讨对晚期乳腺癌有效而经济的化疗方法，以提高患者的生存质量，延长寿命。方法：对36例耐药的晚期乳腺癌患者，采用大剂量顺铂水化疗法进行化疗，并用WHO推荐的标准评价疗效。结果：总有效率100％，其中完全缓解（CR）26例（72．2％），部分缓解（PR）9例（25％），进展（NC）1例（2．8％），无变化（PD）0例。结论：大剂量顺铂水化疗法对耐药的晚期腺癌具有较好的疗效，是一种有效而经济的化疗方案。     

Mitoxantrone as a first-line treatment of advanced breast cancer

Summary Forty-two women with measurable or evaluable advanced breast cancer who had received neither prior chemotherapy for advanced disease nor any anthracycline-containing regimen as adjuvant were entered in a phase II study of mitoxantrone (Novantrone^®; dihydroxyanthracenedione). Patients were aged from 36 to 80 years, performance status was from 0 to 2. All patients had normal hematological status and normal renal and liver function tests. Cardiac scintigraphy and sonography techniques were used to monitor cardiac function. Mitoxantrone was administered at a dose of 14 mg/m² in 100 ml 5% dextrose solution over 30 minutes, repeated every three weeks.The number of courses per patient ranged from 2 to 12. Of 42 eligible patients 39 were fully evaluable for response and all for drug toxicity. Responses to treatment were: complete response four patients, partial response 10 patients, stable disease 18 patients and progressive disease seven patients. The overall response rate was 36% (95% confidence limits 20–52%). Three patients showed decreased left ventricular ejection fraction but no patient developed signs of overt left ventricular failure during the treatment period. Hematological and gastrointestinal toxicities were mild. Hair loss was minimal.The data indicate that mitoxantrone is an effective agent for the treatment of advanced breast cancer with mild side-effects, especially with respect to nausea/vomiting, hair loss and cardiotoxicity.     

ED方案与CEF方案治疗进展期乳腺癌的临床疗效观察

目的 探讨ED方案(表柔吡星+多西他赛)与CEF方案(环磷酰胺+表柔吡星+5-氟尿嘧啶)治疗进展期乳腺癌的临床疗效.方法 选择2013年6月至2015年2月本院收治的进展期乳腺癌患者198例,随机分为ED方案组和CEF方案组,各99例.ED方案组采用表柔吡星+多西他赛治疗方案;CEF方案组采用环磷酰胺+表柔吡星+5-氟尿嘧啶治疗方案;比较两组临床疗效和不良反应.结果 化疗结束后,ED方案组KPS评分明显高于CEF方案组,差异具有统计学意义(t=3.8356,P=0.0002).ED方案组总体有效率为79.80％(79/99),CEF方案组为73.74％(73/99),差异无统计学意义(x2=1.019,P=0.313).两组毒副反应的发生率比较,差异无统计学意义(P＞0.05).结论 表柔吡星+多西他赛治疗治疗进展期乳腺癌近期的临床疗效和不良反应与CEF方案相近,但经过此方案治疗后的患者生活质量更好,值得临床进一步研究.     

多烯紫杉醇联合顺铂治疗晚期乳腺癌疗效观察

目的:观察国产多烯紫杉醇(艾素)联合顺铂治疗晚期乳腺癌的疗效及毒副反应。方法:21例患者均有病理学诊断及可评价的客观指标。采用多烯紫杉醇35mg/m2,静脉滴注1h,第1天、第8天及第15天,顺铂(DDP)为30mg/m2静脉滴注,第2天、第3天及第4天,28d为1个周期,所有患者均至少接受2个周期的化疗。结果:完全缓解(CR)1例,部分缓解(PR)11例,总有效率57.14%。主要毒副反应为骨髓抑制和脱发。结论:多烯紫杉醇联合顺铂治疗晚期乳腺癌有效率较高,毒副反应较小,值得临床进一步研究。     

卡培他滨治疗晚期乳腺癌60例临床观察

目的观察卡培他滨（希罗达）对经蒽环类和（或）紫杉类药物治疗后复发或转移性乳腺癌的疗效分析和毒副反应。方法卡培他滨1250mg/m2,2次/d,餐后服用,连续服用2周,休息1周,至少2周期后评价疗效。结果全组60例无CR,PR16例（26.7%）,SD32例（53.3%）,PD12例（20%）,总有效率26.7%,中位无进展生存时间9.8个月。常见副作用为手足综合征,皮肤色素沉着,腹泻,口腔发炎,恶心呕吐,白细胞及血小板减少,大部分为I-II度。结论应用卡培他滨单药治疗蒽环类和（或）紫杉类治疗后复发或转移性乳腺癌疗效确切,毒副反应轻,应用方便,值得临床推广使用。     

替吉奥治疗晚期乳腺癌的研究进展

替吉奥(S-1)是第三代氟尿嘧啶衍生物的口服抗癌剂,毒副作用小、疗效确切、给药方便。在大量的临床试验及不断的临床应用中,其展示出对晚期乳腺癌(advanced breast cancer,ABC)治疗的良好效果,将来有望成为乳腺癌治疗的一线化疗药物。     

TAC方案治疗晚期乳腺癌的效果观察

目的 观察并分析TAC方案治疗晚期乳腺癌的效果。方法 随机选择2008年1月～2013年12月在本院就诊的58例乳腺癌患者,随机分为对照组和研究组,每组各29例,对照组行CAF方案,研究组行TAC方案,比较分析两组患者的近期疗效与化疗后毒副反应情况。结果 化疗后,研究组腋淋巴结阳性近期疗效为68．42％,对照组腋淋巴结阳性近期疗效为50．00％,研究组明显优于对照组,差异有统计学意义（P〈0．05）。结论 CAF方案治疗晚期乳腺癌腋淋巴结阴性患者具有化疗后毒副作用小、疗效确切的特点,TAC方案治疗晚期乳腺癌腋淋巴结阳性患者具有疗效显著、毒副反应耐受性良好的优势。     

Phase II study of echinomycin in patients with advanced breast cancer: A report of cancer and leukemia group B protocol 8641

Summary Twenty-five women with advanced histologically documented stage IV recurrent or inoperable breast cancer were enrolled on a phase II study of echinomycin administered at a dose of 1.2 mg/m² intravenously over 30 minutes weekly for 4 weeks followed by a two week rest period. Seventy-six percent of patients had visceral dominant disease at study entry and all patients had previously received chemotherapy. One of 21 eligible patients had a partial response lasting 147 days. The median survival for this group of patients was 5.9 months and the median time to treatment failure was 1.7 months. Nausea and vomiting was the primary toxic effect and was severe or life-threatening in 43% of patients. Transient elevation of liver enzymes occurred in 30% of patients. Bone marrow suppression was not significant. Echinomycin as employed in this study did not demonstrate significant antitumor activity in previously treated patients with advanced breast cancer.