卡培他滨联合多西紫杉醇节拍化疗治疗转移性乳腺癌临床研究

目的探讨卡培他滨联合多西紫杉醇节拍化疗治疗转移性乳腺癌临床疗效与安全性。方法20例转移性乳腺癌病例,卡培他滨采用500 mg tid,连续口服第1-14天;国产多西紫杉醇25 mg.m^-2,静脉滴注持续1 h,第1、8 d给药。每21 d重复。结果20例中CR1例,PR11例,SD4例,PD4例,RR为60%（12/20）,DCR为80%（16/20）。不良反应为Ⅰ-Ⅱ度白细胞下降、关节肌肉酸痛及手足综合征,Ⅰ度消化道反应,Ⅲ度不良反应少见,无Ⅳ度不良反应。结论应用卡培他滨联合多西紫杉醇节拍化疗治疗转移性乳腺癌,具有疗效好、副作用小及患者依从性好等优点。     

Combined analysis of two phase II trials in patients with primary and advanced breast cancer with epidoxorubicin and docetaxel+granulocyte colony stimulating factor

Anthracyclines and taxanes are to date the most active cytotoxic agents in the treatment of breast cancer, and a combination of these is therefore considered to result in the highest response rates in the neoadjuvant, as well as in palliative treatment. These two phase II studies aimed to evaluate the feasibility, toxicity and activity of a cytostatic regimen combining epidoxorubicin and docetaxel in outpatient patients suffering from breast cancer. In total, 104 consecutive patients were enrolled in these prospective clinical trials. The chemotherapeutic regimen consisted of epidoxorubicin [75 mg/m2 body surface area (BSA)] and docetaxel (75 mg/m2 BSA) on day 1 accompanied by the administration of granulocyte colony stimulating factor on days 3-10, repeated every 3 weeks (ED+G). Sixty-six patients received ED+G as neoadjuvant and 38 patients as palliative treatment, respectively. Patients received a total of 566 cycles (median: 6 cycles, range: 2-11 cycles) of this therapeutic regimen. Outpatient ED+G was well tolerated. A major response to preoperative ED+G could be demonstrated in 54 of 66 patients (82%) and in 22 of 38 palliative treated patients (58%). We conclude that outpatient ED+G is safe in the neoadjuvant and palliative treatment of patients suffering from breast cancer by showing a favorable side effect and activity profile. Thus, this regimen can be considered for further clinical trials.     

脾多肽联合卡倍他滨/多西紫杉醇治疗蒽环类失败复发转移性乳腺癌的疗效观察

目的 评价脾多肽对采用以卡倍他滨/多西紫杉醇联合化疗方案治疗的蒽环类失败复发转移性乳腺癌的辅助疗效.方法 将63例蒽环类失败复发转移性乳腺癌患者按随机号码表法随机分为两组：脾多肽（斯普林）组（32例）：脾多肽联合卡倍他滨＋多西紫杉醇;对照组（31例）：单用卡倍他滨＋多西紫杉醇.脾多肽组于开始使用联合化疗方案时即行脾多肽（斯普林）10 ml/d（含25 mg多肽）静脉滴注,连续应用4周.分别于治疗前后对患者外周血白细胞、血小板、血红蛋白水平、肝肾功能、食欲、消化道反应、体质量、Karnofsky评分、免疫功能、疗效进行评价.结果 脾多肽组及对照组的总有效率分别是71.9%及54.8%（P=0.014）.脾多肽组及对照组中位生存时间分别为15.9个月及11.3个月（P=0.026）.1年生存率在脾多肽组及对照组分别为51.6%及38.7%（P=0.035）.脾多肽组白细胞、血小板及血红蛋白水平减少程度均好于对照组;免疫指标NK细胞活性,及CD3、CD4、CD8阳性细胞百分率,CD4/CD8比值显著提高（P＜0.05）.结论 脾多肽联合卡倍他滨/多西紫杉醇联合化疗治疗蒽环类失败复发转移性乳腺癌可以增加疗效,减轻骨髓毒性、疼痛及消化道反应,提高机体免疫力,提高患者生存质量和化疗耐受性值得临床推广.     

多西紫杉醇与卡培他滨联合化疗治疗复发转移性乳腺癌疗效观察

目的：探讨多西紫杉醇与卡培他滨联合化疗治疗复发转移性乳腺癌的疗效,为临床治疗提供参考。方法：对本院2009年2月～2011年1月收治的25例乳腺癌患者均采用多西紫杉醇与卡培他滨联合化疗的治疗方案,观察患者的疗效。结果：25例患者中CR2例（8.0%）,PR6例（24.0%）,SD10例（40.0%）,PD7例（28.0%）,总有效率为32.0%。19例患者出现骨髓抑制现象,17例出现恶心、呕吐,9例患者出现口腔黏膜炎,13例患者脱发。结论：多西紫杉醇联合卡培他滨治疗复发转移性乳腺癌患者有较好疗效,不良反应较轻,经治疗很快恢复,值得在临床上进一步观察应用。     

乳腺癌根治术后应用多西紫杉醇联合卡培他滨化疗的临床观察

目的探讨乳腺癌根治术后应用多西紫杉醇联合卡培他滨化疗的临床效果和安全性。方法行乳腺癌根治术的乳腺癌患者67例随机分为对照组和研究组,两组均给予卡培他滨治疗,仅研究组加用多西紫杉醇辅助治疗;分析两组的无进展生存期(RFS)、总生存期(OS)、术后1,2和3年的生存率;分析化疗的髓内、髓外的毒副作用及对心脏的毒性作用。结果研究组的中位RFS和中位OS均长于对照组(P<0.05或0.01),且研究组的术后1,2和3年生存率均高于对照组(P<0.05);除研究组的中性粒细胞减少的发病率和恶心呕吐发病率高于对照组外(P<0.05),其余的髓内、髓外的毒性情况均无统计学差异;研究组的心电图异常例数等与对照组比较均无统计学差异(P>0.05),且两组在心功能异常上(LVEF<50%)也无统计学差异。结论乳腺癌根治术后应用多西紫杉醇联合卡培他滨化疗可延缓乳腺癌的复发,延长患者的总生存期,对髓内、髓外及心脏的毒性作用较小,安全性较高。     

Serum pegfilgrastim concentrations during recovery of absolute neutrophil count in patients with cancer receiving pegfilgrastim after chemotherapy

STUDY OBJECTIVE: To examine the serum concentrations of pegfilgrastim during recovery of absolute neutrophil count (ANC) in patients with cancer who received pegfilgrastim after chemotherapy. DESIGN: Retrospective analysis. DATA SOURCE: Data were pooled from seven pegfilgrastim registrational clinical trials: four open-label phase I or II studies and three randomized phase II or III studies. PATIENTS: A total of 370 patients with non-small cell lung cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, or breast cancer. MEASUREMENTS AND MAIN RESULTS: Chemotherapy was given every 3 weeks, and pegfilgrastim was given once/chemotherapy cycle, 24 hours after chemotherapy completion. Data were available from 187 patients for the serum pegfilgrastim concentration analysis and from 319 patients for the ANC data analysis. Recovery of ANC to normal levels (>or= 1 x 10(3)/mm3) correlated well with the decline of pegfilgrastim concentrations to subtherapeutic levels; this inverse correlation was observed across different tumor types. By day 12 after pegfilgrastim administration, all patients experienced ANC recovery to normal levels, and none had a serum pegfilgrastim concentration above 2 ng/ml, considered the lowest concentration to elicit clinically meaningful granulopoiesis. After administration of pegfilgrastim, a steady postnadir recovery of the ANC to normal levels was noted, and postnadir peaks of 30 x 10(3)/mm3 or higher were observed in only three patients. CONCLUSION: Serum concentrations of pegfilgrastim were consistently cleared to subtherapeutic levels by day 12 after pegfilgrastim administration, and subtherapeutic pegfilgrastim levels were predicted by ANC recovery to 1 x 10(3)/mm3 or greater.     

多西紫杉醇联合顺铂治疗晚期乳腺癌31例临床观察

目的观察多西紫杉醇联合顺铂方案治疗晚期乳腺癌的临床疗效和不良反应。方法晚期乳腺癌31例,其中包括既往应用蒽环类药物治疗18例,非蒽环类药物化疗13例。用多西紫杉醇75mg／m^2,第1天静滴,顺铂25mg／m^2。第1～3天静滴,21天为1周期,2周期后评价疗效。结果31例中CR3例,PR14例,总有效率为54．84％。主要不良反应为骨髓抑制、恶心呕吐和脱发,但均可耐受。结论多西紫杉醇联合顺铂治疗晚期乳腺癌疗效确切,副作用较轻可耐受。     

多西紫杉醇联合顺铂治疗晚期乳腺癌31例临床观察

目的 观察多西紫杉醇联合顺铂方案治疗晚期乳腺癌的临床疗效和不良反应.方法 晚期乳腺癌31例,其中包括既往应用蒽环类药物治疗18例,非蒽环类药物化疗13例.用多西紫杉醇75mg/m2,第1天静滴,顺铂25mg/m2,第1～3天静滴,21天为1周期,2周期后评价疗效.结果 31例中CR3例,PR 14例,总有效率为54.84%.主要不良反应为骨髓抑制.恶心呕吐和脱发,但均可耐受.结论 多西紫杉醇联合顺铂治疗晚期乳腺癌疗效确切,副作用较轻可耐受.     

吉西他滨联合卡培他滨治疗耐药转移性乳腺癌68例临床研究

目的研究吉西他滨联合卡培他滨治疗耐药转移性乳腺癌的临床疗效及不良反应。方法对2008年6月～2010年3月本院入院治疗的68例乳腺癌患者进行了研究,所有患者在经过紫杉醇、蒽环类药物治疗后均无效果．改用吉西他滨和卡培他滨,第1天和第8天静脉滴注吉西他滨,1g/m2,第1～14天口服卡培他滨,2g/m2,分两次服用,3周为1个治疗周期,至少治疗2个周期,观察临床效果及不良反应。结果68例患者中,完全缓解12例．占17．6％,部分缓解22例,占32．4％,稳定18例,占26．5％,进展16例,占23．5％,总有效率为50．0％;不良反应主要表现为腹泻、肝功能损伤和手足综合征,均可以耐受。结论吉西他滨联合卡培他滨治疗耐药转移性乳腺癌临床疗效显著,安全性好,不良反应少,值得临床推广应用。     

多西他赛、奥沙利铂联合卡培他滨新辅助化疗对进展期胃癌的疗效

目的：探讨多西他赛、奥沙利铂联合卡培他滨（简称DOX方案）新辅助化疗在进展期胃癌中的临床疗效及不良反应。方法：对2008-06-01至2011-05-31于第二军医大学长征医院胃肠外科就诊的186例进展期胃癌病人,应用多西他赛75mg/m2,静脉滴注,第1天;奥沙利铂130mg/m2,静脉滴注,第2天;卡培他滨1 000mg/m2,口服,bid,第1天至第14天;3周为1个疗程,共2～3个疗程,化疗结束后2～3周手术。结果：总有效率67.8%,完全缓解7例（3.8%）,部分缓解119例（64.0%）,手术切除率81.5%,R0切除率80.4%。主要不良反应为骨髓抑制和恶心、呕吐。结论：多西他赛、奥沙利铂联合卡培他滨方案新辅助化疗治疗进展期胃癌可以提高手术的根治性切除率,其不良反应发生率尚在可接受范围。     

Single-agent capecitabine maintenance therapy after response to capecitabine-based combination chemotherapy in patients with metastatic breast cancer

We performed an analysis of the efficacy of capecitabine monotherapy as maintenance treatment for metastatic breast cancer (MBC) after response to capecitabine-based chemotherapy [capecitabine plus docetaxel (XT) or vinorelbine (XN)] as a first-line or a second-line treatment. Sixty-four Chinese patients with histologically confirmed MBC received capecitabine maintenance therapy after disease stabilization or maximal response to capecitabine-based combination chemotherapy. Single-agent capecitabine was administered at a dose of 1000 mg/m(2) twice daily for 14 days, followed by a 7-day rest period, every 3 weeks. The median time to progression, the primary endpoint of the study, was 4.4 months (95% confidence interval, 3.4-5.4 months). Fifty-nine patients were evaluable for response. Capecitabine maintenance therapy produced an objective response rate of 5.1% (95% confidence interval, 3.9-6.3%). The incidence of grade 3/4 leukopenia (3.1%) and neutropenia (4.7%) was significantly lower (P<0.001) with capecitabine monotherapy than with combination chemotherapy (46.9 and 54.7%, respectively). Conversely, the incidence of grade 3 hand-foot syndrome was higher with capecitabine maintenance therapy than with combination therapy (14.1 vs. 0%, respectively; P=0.003). Capecitabine monotherapy is an effective maintenance treatment after response to capecitabine-based combination chemotherapy in MBC with a favorable safety profile.     

多烯紫杉醇在乳腺癌患者体内的药代动力学研究

目的研究多烯紫杉醇在乳腺癌患者体内的药代动力学。方法 10例乳腺癌患者采用多烯紫杉醇75 mg·m~(-2)静脉滴注1 h化疗,在化疗后不同时间采集血液标本,用HPLC法测定多烯紫杉醇血药浓度,用DAS 3.0软件计算药代动力学参数。结果多烯紫杉醇的血浆药物峰浓度Cmax均值为(3.345±1.05)mg·L~(-1),血药浓度-时间曲线下面积AUC0~12 h均值为(3.247±0.91)mg·h·L~(-1),消除半衰期t1/2均值为(9.602±3.72)h,清除率CL均值为(18.718±3.84)L/(h·m)-2。药动学参数在患者个体间存在较大差异。结论多烯紫杉醇在乳腺癌患者体内的药代动力学存在较大个体差异,提示在临床用药时需要监测多烯紫杉醇的血药浓度,进行个体化给药。     

Pathological complete response rates comparing 3 versus 6 cycles of epidoxorubicin and docetaxel in the neoadjuvant setting of patients with stage II and III breast cancer

We conducted a prospective randomized study to compare the results of 3 cycles of epidoxorubicin/docetaxel to 6 cycles of epidoxorubicin/docetaxel prior to surgery in breast cancer patients with clinical stages II and III. Forty-five patients eligible for neoadjuvant chemotherapy were randomly assigned to receive either 3 (group 1) or 6 (group 2) cycles of epidoxorubicin/docetaxel prior to surgery. Chemotherapy consisted of epidoxorubicin 75 mg/m and docetaxel 75 mg/m on day 1 in 3-week cycles. The primary endpoint was the pathological complete response (pCR) rate; secondary endpoints were the rates of breast-conserving surgery and the axillary lymph node status in both groups. A pCR occurred in 10% (two of 20) in Group 1 and in 36% (nine of 25) in Group 2, which was statistically significant (p=0.045). Breast-conserving surgery could be performed in 70% (14 of 20) in Group 1 and in 76% (19 of 25) in Group 2 (p=0.065). Axillary lymph node status was negative in 45% (nine of 20) in Group 1 and 52% (13 of 25) in Group 2 (p=0.86). We conclude that 6 cycles of pre-operative epidoxorubicin/docetaxel versus 3 cycles of pre-operative epidoxorubicin/docetaxel significantly increases the pCR rates for breast cancer patients.     

Alternating intravenous and oral vinorelbine plus epirubicin with pegfilgrastim as neoadjuvant treatment of locally advanced breast cancer

In order to downstage locally advanced breast cancer, neoadjuvant chemotherapy consisting of intravenous vinorelbine 25 mg/m plus epirubicin 75 mg/m given on day 1 and oral vinorelbine 60 mg/m on day 8 was administered every 3 weeks for four courses. On day 2, all patients received a single subcutaneous injection of pegfilgrastim (6 mg). From March 2004 to June 2005, 22 patients were enrolled. Patients characteristics were: median age, 53 years (range: 39-70 years); postmenopausal, 7/22; clinical TNM stage, T2 (n=14), T3 (n=8), N0 (n=17) and N1 (n=5). The median number of courses was four (range: two to six courses) with full dose intensity. National Cancer Institute grade 3 haematological toxicities observed were neutropenia in 9% of patients, anaemia in 13% of patients and thrombocytopenia in 9% of patients; no toxicity grade 4 occurred. Two patients (9%) registered grade 2 polyneuropathy; no cardiac failure was observed. Conservative surgery was performed in 14 patients (63%). All patients were evaluable for response: complete pathological response was documented in three patients (13.6%); three patients (13.6%) obtained more than 75% of tumour size reduction; 11 other patients (50%) had 50% of tumour size reduction; stable disease was observed in five patients (22.7%). The present findings indicate that vinorelbine in combination with epirubicin is an effective and safe treatment in locally advanced breast cancer: this regimen obtained more than 50% of tumour size reduction in 77% of patients; the use of pegfilgrastim allowed full dose intensity. Oral vinorelbine on day 8 offers greater convenience to the patient by reducing the need for intravenous injection and the time spent in hospital.     

紫杉醇联合表阿霉素双周方案治疗转移性乳腺癌32例

目的观察紫杉醇联合表阿霉素(TE)双周方案治疗转移性乳腺癌的近期疗效与毒副反应。方法32例转移性乳腺癌患者采用TE方案化疗,表阿霉素40mg/(m2.d)第1、2天静脉滴注,紫杉醇85mg/m2第3天静脉滴注,14天为一周期,完成2～4个周期,评价疗效和毒副反应。结果CR5例,PR19例,NC8例,无PD,有效率(RR)为75.00%,其中初治组有效率为91.67%,复治组为65.00%(P<0.05),差异有统计学意义,初治组有效率高于复治组。主要剂量限制性毒性为骨髓抑制,Ⅲ～Ⅳ度骨髓抑制发生率为40.63%(13/32),所有患者均需要使用G-CSF支持治疗。结论TE双周方案治疗转移性乳腺癌疗效好,毒副反应可耐受,是治疗晚期乳腺癌较好的方案。     

Dose-dense primary systemic chemotherapy with gemcitabine plus epirubicin sequentially followed by docetaxel for early breast cancer: final results of a phase I/II trial

We recruited 50 patients with T2-4 N0-2 M0 primary breast cancer into a phase I/II study to define the maximum tolerated dose (MTD), efficacy and tolerability of preoperative gemcitabine (1250 mg/m fixed dose) plus epirubicin (doses escalated from 90 mg/m) for 5 cycles followed by 4 cycles of docetaxel (scheduled fixed dose 100 mg/m) given on day 1 every 2 weeks (q2w) with pegfilgrastim support. The MTD for epirubicin was 100 mg/m, but the docetaxel dose had to be reduced to 80 mg/m. Dose-limiting toxicities included fatigue, stomatitis, diarrhea and dyspnea (all grade 3) during gemcitabine plus epirubicin, and fatigue (grade 3) and allergic reaction (grade 4) during docetaxel treatment, respectively. A pathologic complete response could be achieved in 13 patients (pT0+pTis, 26%), and in the breast and axilla in 12 patients [(pT0 or pTis)+pN0, 24%). Breast-conserving surgery (BCS) was possible in 35 patients (70%). Main grade 3/4 adverse events at MTD were fatigue (57/0%), leukopenia (27/8%), and liver (14/0%) and lung toxicity (14/0%). In conclusion, gemcitabine plus epirubicin 1250/100 mg/m q2w followed sequentially by docetaxel 80 mg/m q2w is highly effective as pre-operative chemotherapy with manageable toxicity. However, response and BCS rates could not be increased by administering gemcitabine plus epirubicin and docetaxel in a dose-dense fashion.     

Safety and efficacy of pegfilgrastim in children with cancer receiving myelosuppressive chemotherapy

The myelotoxicity of most chemotherapeutic regimens used to treat children and adolescents with cancer require the use of daily subcutaneous administration of hematological growth factors (mainly granulocyte colony-stimulating factor). Recently, pegfilgrastim (Neulasta), a product with a long half-life, resulting in once-per-cycle dosage, was introduced to prevent neutropenia in adults, and provided safety and efficacy similar to that provided by daily injection of filgrastim. To evaluate retrospectively the use of pegfilgrastim in children with cancer, we conducted a single-center retrospective study evaluating the use of pegfilgrastim in patients over 40 kg, who received chemotherapy for cancer from September 2003 to December 2005. A single subcutaneous injection of pegfilgrastim 100 microg/kg (maximum dose 6 mg) per chemotherapy cycle in children receiving myelosuppressive chemotherapy was given. One hundred and twenty-six administrations of pegfilgrastim were analyzed in 28 pediatric patients treated for cancer (11 girls, 17 boys) with a median age of 14.5 years (range 12-18 years) and median weight of 50.5 kg (range 40-82 kg). Patients received a median dose of pegfilgrastim of 100 microg/kg (range 73-117). The median total number of injections per patient was 4 (range 1-14). The incidence of grade 4 neutropenia by cycle was 48%, the mean duration of neutropenia was 3 days (range 1-13 days). The median values of absolute neutrophil count nadir was 0.425 x 10(9)/l (range 0-9.9 x 10(9)). Febrile neutropenia occurred in 18 of the 126 patients on pegfilgrastim use (14%) with full recovery in all patients. The median total duration of intravenous antibiotic therapy was 5 days (range 2-14 days). Bone pain (four) and headaches (two) were the most frequent adverse events reported. No correlation was found between the administered dose of Neulasta and hematological data. In conclusion, the use of pegfilgrastim was safe and well tolerated in children with cancer treated with myelosuppressive chemotherapy. Safety and efficacy of pegfilgrastim must be compared with filgrastim and evaluated in younger children with lower body weight.     

A randomized phase II trial comparing preoperative plus perioperative chemotherapy with preoperative chemotherapy in patients with locally advanced breast cancer

The aim of this study was to investigate in a randomized trial the activity of perioperative chemotherapy in patients treated with preoperative chemotherapy for locally advanced breast cancer and to compare it with the preoperative chemotherapy alone. Patients with cT2-3 N0-2 M0 histologically proven breast cancer, with estrogen receptors and progesterone receptors in less than 20% of cells, or with absence of progesterone receptors, received epirubicin 25 mg/m days 1 and 2, cisplatin 60 mg/m day 1, and fluorouracil 200 mg/m daily as continuous infusion. Responding patients were randomized to continue fluorouracil until 2 weeks after surgery (perioperative chemotherapy) or to stop fluorouracil 1 week before surgery. Fifty-eight patients completed six courses of epirubicin, cisplatin and fluorouracil, and were randomized to perioperative chemotherapy (29 patients) or to control (29 patients). The median Ki-67 index remained stable (32-27.5%) in the perioperative chemotherapy arm (P=0.3) and decreased from 55 to 22.5% in the control arm (P=0.01). The rate of pathological complete remission was 41% in both arms (P=1.0). No significant difference in terms of disease-free survival and overall survival was observed between the two arms. Perioperative chemotherapy failed to show an increase in the pathological complete remission rate. A biological effect on Ki-67 expression was demonstrated.     

探讨高龄乳腺癌患者术后早期应用多西他赛辅助化疗的安全性

目的：探讨高龄乳腺癌患者术后早期应用多西他赛辅助化疗的安全性。方法：将2010年2月～2012年2月于我院接受治疗的60例年龄超过70岁的乳腺癌患者作为研究对象,随机将其分为对照组与观察组各30例,对观察组患者于术后3d开始应用多西他赛每周辅助化疗方案,对照组患者术后2周开始给予相同的辅助化疗方案,对比观察两组化疗效果。结果：两组患者在接受化疗治疗后,血清内白细胞水平均得到不同程度的下降,治疗六周后观察组白细胞水平为[（3.59±0.91）×109/L],下降趋势较对照组明显,差异显著（t=9.365,P＜0.05）;观察组术后创口愈合时间为（10.31±2.56）d,对照组为（10.51±3.11）d,两组患者术后创口愈合时间对比并无显著差异（t=0.157,P＞0.05）。结论：对高龄乳腺癌术后治疗宜选用早期多西他赛每周化疗方案,在降低肿瘤复发可能性的同时能够提高治疗效果,提升患者的生存质量,值得推广。