Weekly paclitaxel as first-line chemotherapy and trastuzumab in patients with advanced breast cancer

Aim:to evaluate the activity and acute toxicity of thecombination of weekly paclitaxel as first-line chemotherapy andtrastuzumab, in patients with HER-2/neu overexpressing advanced breastcancer (ABC). Background:Weekly paclitaxel has beenshown to be a well tolerated treatment with considerable activity inpatients with ABC. Clinical trials with transtuzumab, a humanizedanti-p185 HER-2/neu monoclonal antibody have demonstrated that thisagent produces objective responses in patients with ABC. Patients and methods:From December 1998 to April 2000, 34patients with HER-2/neu overexpressing ABC were treated with weeklypaclitaxel; given by one-hour infusion at a dose of 90 mg/m²immediately followed by trastuzumab, 4 mg/kg as a loading dose and2 mg/kg i.v. given over 30 min, thereafter weekly for at least 12 weeks.Expression of HER-2/neu was determined by immunohistochemical analysison fixed, paraffin-embedded tissues. Eligible patients were required tohave 25% stained tumor cells. Results:Thirty-three patients completed at least 12 weeks of combinedtreatment. After completion of the 12th week of treatment, four patients(12%) achieved complete and 17 (50%) partial response.Median duration of response was 11.6 months. More frequent side effectsincluded anemia (56%), neutropenia (27%), peripheralneuropathy (78%), diarrhea (30%), alopecia (70%),arthralgias/myalgias (62%), fatigue (59%) andhypersensitivity reactions (62%). Median time to progression wasnine months while median survival had not been reached Conclusions:The combination of weekly paclitaxel andtrastuzumab is a safe and active regimen for patients with HER-2/neuoverexpressing ABC. Randomized phase III studies with this combinationare warranted.     

吉西他滨联合顺铂二线治疗晚期乳腺癌

目的观察国产吉西他滨(泽菲)联合顺铂组成的GP方案二线治疗蒽环类或紫杉类耐药性晚期乳腺癌的疗效与安全性。方法2003~2005年以GP方案治疗蒽环类或紫杉类耐药性晚期乳腺癌29例,泽菲1250mg/m2静滴,第1、8天,顺铂80mg/m2静滴,第1天,每21天为1周期。以WHO标准评价疗效和毒性。结果29例患者,中位化疗周期数为3周期(2~4周期),其中CR1例(3·4%),PR14例(48·3%),SD8例(27·6%),PD6例(20·7%),有效率为51·7%。随访2年,中位TTP35周(12~44周),中位生存期为62周(45~81周)。主要毒性反应为恶心、呕吐与骨髓抑制。结论国产吉西他滨和顺铂联合方案治疗蒽环类或紫杉类耐药性晚期乳腺癌疗效较好,使用方便,毒性反应较轻,是二线治疗蒽环类或紫杉类耐药性晚期乳腺癌的有效解救方案。     

An exploratory study of sunitinib plus paclitaxel as first-line treatment for patients with advanced breast cancer

BackgroundSunitinib has shown single-agent activity in patients with previously treated metastatic breast cancer (MBC). We investigated the safety of the combination of sunitinib and paclitaxel in an exploratory study of patients with locally advanced or MBC.MethodsPatients received oral sunitinib 25 mg/day (with escalation to 37.5 mg/day as tolerated) on a continuous daily dosing schedule and paclitaxel 90 mg/m² on days 1, 8, and 15 of each 28-day cycle. Study endpoints included safety (primary endpoint), pharmacokinetics, and antitumor activity.ResultsTwenty-two patients were enrolled. The most frequent adverse events (AEs) were fatigue/asthenia (77%), dysgeusia (68%), and diarrhea (64%). Grade 3 AEs included neutropenia (43%), fatigue/asthenia (27%), neuropathy (18%), and diarrhea (14%). No drug–drug interaction was observed on the basis of pharmacokinetic analysis. Of 18 patients with measurable disease at baseline, 7 (38.9%) achieved objective responses (including 2 complete and 5 partial responses). Clinical responses were observed in three of nine patients with triple-negative receptor status (estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor-2 negative).ConclusionsThese data indicate that sunitinib and paclitaxel in combination are well tolerated in patients with locally advanced or MBC. No drug–drug interaction was detected and there was preliminary evidence of antitumor activity.     

Weekly one-hour paclitaxel as first-line chemotherapy for metastatic breast cancer

In this first reported study of weekly paclitaxel administered as first-line chemotherapy for metastatic breast cancer, paclitaxel 100 mg/m² was administered in a 1-h infusion on a weekly basis to 35 patients who may previously have received adjuvant chemotherapy (but not taxane-containing regimens), but not for advanced or metastatic disease. A median of 14 infusions per patient was given at a mean delivered dose intensity of 94 mg/m² per week. In 33 assessable patients, a complete response (CR) was observed in 1 patient and partial responses (PRs) in 12 patients, producing an overall response rate of 40%. Stable disease (SD) was observed in 17 patients, of whom 9 were stabilized for more than 24 weeks. Thus, clinical benefit (CR+PR+SD_{≥24 weeks}) was observed in 67% of the patients. Time to progression was 189 days, the duration of response 180 days and overall survival 544 days. Five patients developed grade 3 neutropenia and five patients grade 3 neurotoxicity. Thus, this study has shown that weekly paclitaxel as first-line therapy for metastatic or advanced breast cancer produces comparable response rates and less toxicity than when the drug is given every three weeks.     

Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer

In this phase II, multicentre trial, patients with metastatic breast cancer (MBC) were treated with a combination of gemcitabine, epirubicin and paclitaxel (GET). The primary objective of this study was to determine the tolerability and activity in terms of complete responce (CR) and overall response rate of the GET combination in this patient population. Patients with no prior treatment for MBC, and at least one bidimensionally measurable lesion received gemcitabine 1000 mg m(-2) intravenously (i.v.) over 30 min on days 1 and 4, followed by epirubicin i.v. at 90 mg m(-2) on day 1, and paclitaxel 175 mg m(-2) over 3 h on day 1, every 21 days, up to eight courses. From May 1999 to June 2000, 48 patients were enrolled from seven Italian institutions. A total of 297 chemotherapy courses were administered with a median of six cycles patient(-1) (range 1-8). Seven patients (15%) obtained CR and 27 patients (56%) had partial responce, for an overall response rate of 71% (95% CI: 58.3-83.7). After a median follow-up of 23.7 months (range 7.0-34.4), median progression-free survival was 10.5 months (95% CI: 9.2-11.7), and median overall survival 25.9 months. The main haematological toxicity consisted of grade 3 or 4 neutropenia that occurred in 62% of cycles (22% grade 4 and 40% grade 3). The GET combination is active and well tolerated as first-line chemotherapy for MBC.     

Gemcitabine plus Epi-doxorubicin as first-line chemotherapy for bladder cancer in advanced or metastatic stage: a phase II

Combination chemotherapy with newer, more active drugs in patients with advanced and/or metastatic bladder cancer might show improved response rate and survival. Gemcitabine (GEM) and Epidoxorubicin (EPI) have demonstrated activity in this disease. In addition, experimental studies in vitro have shown that the two agents have additive-synergistic effects when used in combination. Our prior phase I dose-finding study in previously untreated patients with advanced or metastatic bladder cancer defined recommended doses for further trials of GEM 1000 mg/m2 and EPI 25 mg/m2 on days 1, 8 and 15 every 28 days. A phase II trial at this dose level was initiated in previously untreated patients to assess efficacy and toxicity. Eligible patients had measurable disease; Karnofsky performance status (PS) of > 40; no prior chemotherapy; and adequate bone marrow reserve, cardiac, hepatic and renal function. Thirty- one patients (22 males, 9 females) with median age of 64 (range 44-75) and median PS of 80 were accrued, and all were eligible. Twelve patients had T4N1-2 M0, 8 had lymph node only metastases, while 11 had visceral metastases (liver, bone, lung). A total of 181 cycles was administered (range 3-7 per patient). Major toxicities (WHO grade > or = 3) were: neutropenia in 5 patients, thrombocytopenia in 2 patients, and anemia in 2 patients. Three patients had febrile neutropenic episodes and only 3 patients required dose reduction. Grade 1-2 non-hematological toxicities included nausea/vomiting, stomatitis and alopecia. No cardiac toxicity was observed. Of the 30 response evaluable patients, 17 (57%) demonstrated a major response (3 complete and 14 partial) (95% CI: 39%-75%), 7 had stable disease (23%) and 6 progressed (20%). These preliminary results confirm the phase I observation that the combination of GEM--EPI is highly active in the treatment of advanced and metastatic bladder cancer with a favourable toxicity profile.     

吉西他滨联合卡培他滨二线治疗晚期乳腺癌

背景与目的：含蒽环类或紫杉类药物的化疗方案是治疗晚期乳腺癌较佳的方案,但临床有20%～30%的患者疗效不佳,对这部分患者二线化疗目前无统一标准方案.本研究探讨既往接受过蒽环类和紫杉类药物治疗失败的晚期乳腺癌患者,使用吉西他滨联合卡培他滨方案治疗的疗效和毒性.方法：吉西他滨1 000 mg/m2,静脉滴注,第1、8天;卡培他滨950 mg/m2口服,每日2次,第1～14天;每3周为一周期,至少应用2疗程,评价临床疗效和毒性,并进行随访.结果：30例女性患者入本研究,疗效均可评价,CR 2例（6.7%）,PR 12例（40.0%）,SD 13例（43.3%）,PD 3例（10.0%）,总有效率（CR﹢PR）46.7%, 中位无进展生存期9个月,中位生存期12.5个月.主要毒性是骨髓抑制和手足综合征.结论：吉西他滨联合卡培他滨化疗方案二线治疗晚期乳腺癌有较好疗效,毒性可耐受.     

Gemcitabine plus docetaxel as first-line chemotherapy in patients with advanced non-small cell lung cancer: a lung cancer Galician group phase II study

Background Numerous phase II and III clinical trials have demonstrated a higher activity of combined gemcitabine plus docetaxel schedules against non-small cell lung cancer (NSCLC) than that of both agents in monotherapy. Methods This phase II study evaluated a 3-week based schedule of docetaxel 85 mg/m² (1-h i.v. infusion, d8) combined with gemcitabine 1,000 mg/m² (30-min i.v. infusion; d1,8) as first-line chemotherapy for patients with advanced NSCLC. Results Forty-one patients with non-resectable, stage IIIB/IV, and bidimensionally measurable disease were enrolled. A total of 182 chemotherapy cycles (median 6, range 1–6) was administered to 40 patients during the study; one patient did not receive chemotherapy due to a protocol deviation. Two patients were not evaluable for treatment efficacy. The overall response rate found was 44% (95% CI, 29–59%): three patients (7%) had a complete response and 15 patients (37%) had a partial response (median duration of response = 4.0 months). With a median follow-up of 8.7 months, the median time to disease progression was 4.4 months and the median overall survival was 7.3 months. The combined gemcitabine plus docetaxel chemotherapy was well tolerated except for pulmonary toxicity. The main grade 3–4 hematological toxicity was neutropenia (28% of patients, 9% of cycles). Two cases of febrile neutropenia were reported. The main grade 3–4 non-hematological toxicity was pulmonary toxicity (23% of patients, 6% of cycles). Conclusion Gemcitabine 1,000 mg/m² on days 1 and 8 in combination with docetaxel 85 mg/m² on day 8 given in 3-week cycles is an active and well-tolerated first-line chemotherapeutic regimen for advanced NSCLC.     

多西他赛联合表阿霉素与多西他赛联合顺铂一线治疗晚期乳腺癌的临床研究

目的 评价多丙他赛联合表阿霉素(TE方案)与多西他赛联合顺铂(TP方案)一线治疗局部晚期或转移性乳腺癌患者的疗效和安全性.方法 88例患者按2:1随机进入TE组和TP组.TE组患者药物剂量为多西他赛75 mg/m2,表阿霉素60 mg/m2;TP组患者药物剂量为多西他赛75mg/m2,顺铂75 mg/m2. 21 d为1个周期,2个周期末评价近期疗效及安全性.结果 TE组可评价近期疗效者55例,其中CR 3例,PR 26例,SD 22例,PD 4例.TP组可评价近期疗效者27例,其中CR 1例,PR 16例,SD 9例,PD 1例.TE组和TP组近期有效率分别为48.3%和60.7%(P=0.2788),临床受益率分别为85.0%和92.9%(P=0.4899),中位肿瘤进展时间(TTP)分别为10个月和8个月(P=0.7119).Ⅲ、Ⅳ度不良反应主要为中性粒细胞减少,TE组和TP组发生率分别为66.7%和53.6%(P=0.2373);其次为脱发,TE和TP组分别为30.0%和10.7%(P=0.0508).结论 TE方案与TP方案一线治疗局部晚期或转移性乳腺癌的疗效和安全性相当.     

长春瑞滨联合紫杉醇治疗晚期乳腺癌

背景与目的：长春瑞滨（商品名诺维本、NVB）其作用阻滞微管蛋白聚合和诱导微管的解聚，而紫杉醇相反，它促进微管蛋白的聚合，阻微管正常的生理性解聚：本文观察长春瑞滨联合紫杉醇治疗晚期乳腺癌的临床疗效疗效和毒副反应方法：42例经病理学和细胞学证实的晚期乳腺癌患者应用长春瑞滨25mg/m^2，静脉滴注，第1、8d；紫杉醇175mg/m^2，静脉滴注3h，第1天；在紫杉醇静脉滴注之前12h、6h，分别口服地塞米松20mg，给药前30min肌注非那根25mg和西米替丁300mg静脉滴注。21d为一个周期，完成2～4个周期后评价疗效：结果：全组总缓解率（RR）66．7％，填中完全缓解率（CR）16．7％，初次化疗患者RR72．2％，CR27．7％；再次化疔患者RR62．1％，CR8．3％，2，4年生存率分别为40．5％（17／42）和21．4％（9／42）；中位缓解期为8个月（5～17个月），中化生存期为18个月；主要毒副反应为骨髓抑制，脱发和周围静脉炎：结论：长春瑞滨联合紫杉醇方案治疗晚期乳腺癌有很好的疗效，且毒副反心患者可耐受。     

紫杉醇联合顺铂一线治疗晚期食管癌疗效及预后分析

目的:探讨紫杉醇联合顺铂一线治疗晚期食管癌的疗效及安全性.方法:回顾性分析2008年1月至2013年6月我院收治的以紫杉醇联合顺铂作为一线化疗方案的晚期食管癌患者的临床及病理资料,根据上述纳入患者的性别、年龄、肿瘤位置、肿瘤分化程度、肿瘤进展情况等一般资料,按1∶1的比例选取同期以多西他赛联合顺铂作为一线化疗方案的晚期食管癌患者进行配对.比较病例组(紫杉醇联合顺铂)和对照组(多西他赛联合顺铂)一线化疗不良反应发生情况及生存情况的差异.结果:病例组因食管癌及其相关疾病死亡26例,存活14例,一线化疗后进展27例.PFS 3~30.5个月,中位PFS 10.7个月.OS 2~31个月,中位OS 13个月.对照组因食管癌及其相关疾病死亡25例,存活15例,一线化疗后进展30例.PFS 2.9~47个月,中位PFS 12个月.OS 1~49个月,中位OS 10个月.两组患者PFS及OS的差异,具有统计学意义(P<0.05).单因素和多因素分析显示,除临床分期和初治时远处转移器官数目外,一线化疗方案中紫杉醇联合顺铂与否也是影响两组患者PFS和OS的独立预后因素.结论:与多西他赛联合顺铂相比,紫杉醇联合顺铂一线治疗晚期食管癌的疗效显著,对于进展期食管癌患者来说是一个可供选择的一线治疗方案.     

Vinorelbine and paclitaxel as first-line chemotherapy in metastatic breast cancer.

PURPOSE: To evaluate the efficacy and toxicity of a combination of vinorelbine (VNB) and paclitaxel (PTX) as first-line chemotherapy in metastatic breast carcinoma (MBC). PATIENTS AND METHODS: Between August 1995 and August 1997, 49 patients with untreated MBC received a regimen that consisted of VNB 30 mg/m2 in a 20-minute intravenous (IV) infusion on days 1 and 8 and PTX 135 mg/m2 in a 3-hour IV infusion (starting 1 hour after VNB) on day 1. Cycles were repeated every 28 days. The median age of the patients was 52 years, and 59% of patients were postmenopausal. Median performance status was 1. Dominant sites of disease were soft tissue in 6%, bone in 29%, and viscera in 65%. RESULTS: Objective responses were recorded in 27 of 45 assessable patients (60%; 95% confidence interval, 46% to 74%). Complete remissions occurred in three patients (7%), and partial remissions occurred in 24 patients (53%). No change was recorded in 12 patients (27%), and progressive disease occurred in six patients (13%). The median time to treatment failure was 7 months, and median survival duration was 17 months. The limiting toxicity was myelosuppression, mainly leukopenia in 49 patients (100%) (grade 1 to grade 2, four patients; grade 3, 30 patients; and grade 4, 15 patients). Neutropenia was observed in 100% of patients (grade 1 to grade 2, three patients; grade 3, 11 patients; grade 4, 35 patients). Two treatment-related deaths due to febrile neutropenia were observed in patients with massive liver involvement. Peripheral neurotoxicity developed in 33 patients (67%) (grade 1, 25 patients; grade 2, eight patients); there were no grade 3 or grade 4 episodes. CONCLUSION: The combination of VNB-PTX showed significant activity as first-line chemotherapy for patients with MBC. Myelosuppression was the dose-limiting side effect, whereas neurotoxicity was mild to moderate.     

SOX方案联合阿帕替尼一线治疗晚期胃癌的临床研究

目的 观察替吉奥、奥沙利铂联合阿帕替尼在晚期胃癌一线治疗中的临床疗效。方法 选择2015年2月至2016年10月于新疆维吾尔自治区人民医院就诊的晚期胃癌患者88例，随机分为试验组和对照组，每组44例。对照组给予替吉奥联合奥沙利铂（SOX方案）化疗，试验组在对照组的基础上应用阿帕替尼，比较两组患者的近期疗效、不良反应及生存情况。结果 试验组患者的客观缓解率明显高于对照组（40.91% vs 20.45%，χ²=4.238，P=0.037），疾病控制率与对照组比较差异无统计学意义（86.36% vs 70.45%，χ²=3.289，P=0.070）。试验组中位总生存期较对照组长（12个月 vs 9.5个月，χ²=4.254，P=0.039），中位无疾病进展生存期亦较对照组长（9个月 vs 6个月，χ²=8.815，P=0.003）；试验组高血压和手足综合征总发生率高于对照组（P＜0.05），其余不良反应发生率差异无统计学意义（P＞0.05）。结论 替吉奥和奥沙利铂联合阿帕替尼一线治疗晚期胃癌患者可取得较好的临床疗效，能有效延长患者的生存期和疾病进展时间，且安全性良好。     

A phase II study of paclitaxel plus carboplatin as first-line chemotherapy for women with metastatic breast carcinoma

BACKGROUND: This Phase II multicenter study evaluated the efficacy and toxicity of paclitaxel (200 mg/m(2) by 3-hour infusion) with carboplatin (area under the curve 6 mg/mL per minute) administered every 3 weeks as first-line therapy for women with metastatic breast carcinoma. METHODS: Eligible patients had measurable metastatic disease and an Eastern Cooperative Oncology Group performance status of 0-2. Prior adjuvant chemotherapy, including anthracycline-based therapy, was allowed, as was prior hormonal therapy as part of either adjuvant treatment or treatment for metastasis. Prior therapy with taxanes or platinum was not allowed. RESULTS: A total of 53 patients were enrolled in this study, with 50 patients evaluable for response and toxicity. The overall response rate was 62% (95% confidence interval ?CI, 48-75%); 16% of patients had complete responses and 46% had partial responses. The median time to progression was 7.3 months (95% CI, 5.9-12.9), and the 12-month survival estimate was 72% (95% CI, 61-86%). Therapy was generally well tolerated. Grade 3-4 neutropenia was the predominant toxicity, observed in 82% of patients, but there were no episodes of febrile neutropenia or sepsis. Hematopoietic growth factors were not routinely necessary. Grade 3 peripheral neuropathy occurred in 16% of patients. CONCLUSIONS: Paclitaxel (200 mg/m(2)) with carboplatin (area under the curve 6 mg/mL per minute) demonstrated substantial efficacy in patients with metastatic breast carcinoma, and the 12-month survival rate of 72% was encouraging. This therapy represents a viable option for patients with metastatic disease.     

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer

Background A randomized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2. Patients and methods Among 124 patients randomized, 123 are assessable for toxicity and 118 for response. Patients received weekly paclitaxel single agent (80 mg/m²) or combined with trastuzumab (4 mg/kg loading dose, then weekly 2 mg/kg). HER-2 overexpression was determined by immunohistochemistry (IHC). Patients with 2+/3+ IHC scores were eligible. IHC was compared with HER-2 serum extracellular domain (ECD). Results Patient characteristics were similar in the two arms. Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity. No patient developed cardiac toxicity. The combined treatment was statistically significant superior for overall response rate (ORR) (75% vs. 56.9%; P = 0.037), particularly in the subset of IHC 3+ patients (84.5% vs. 47.5%; P = 0.00050). A statistically significant better median time to progression was seen in the subgroup with IHC 3+ (369 vs. 272 days; P = 0.030) and visceral disease (301 vs. 183 days; P = 0.0080) treated with combination. Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR (P = 0.0035). Conclusion Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3+.     

Weekly paclitaxel as first-line chemotherapy for elderly patients with metastatic breast cancer. A multicentre phase II trial

Paclitaxel is a cytotoxic agent with proven antitumour activity in metastatic breast cancer. Weekly administration of paclitaxel has demonstrated sustained efficacy together with a more favourable toxicity profile (e.g. less myelotoxicity) than the 3-weekly administration. This study evaluates the activity and toxicity of weekly paclitaxel (Taxol(R)) as first-line chemotherapy in elderly patients (>70 years of age) with hormone-refractory metastatic breast cancer. Patients with metastatic breast cancer received 80 mg/m(2) paclitaxel administered weekly on days 1, 8 and 15 of a 28-day cycle. Additional cycles were given until disease progression, or unacceptable toxicity. A dose increase to 90 mg/m(2) was allowed in the absence of toxicity. 26 Patients received a total of 101 cycles (median 4, range 1-11). 22 patients completed at least two cycles (six administrations). In 23 patients who were evaluable for response, there were 10 partial responses (38%), 9 patients with stable disease (35%), while 4 patients had disease progression (15%). The median duration of response was 194 days (>6 months). Overall treatment was relatively well tolerated, but 8 patients (32%) had to prematurely discontinue treatment because of fatigue. Neuropathy >grade 1 was noted only after five or more cycles in 4 patients. Weekly paclitaxel at this dose and schedule is an effective treatment regimen in the elderly patient with metastatic breast cancer, and is feasible, but yields relevant fatigue in a subset of patients.