Docetaxel in patients with anthracycline-resistant advanced breast cancer

OBJECTIVE: To better determine docetaxel activity in patients with well-defined anthracycline-resistant breast cancer. METHODS: From October 1996, we carried out a phase II trial in 69 heavily pretreated patients with advanced breast cancer with docetaxel 100 mg/m(2) by a 1-hour infusion on day 1, with cycles repeated every 3 weeks. Patients were classified as having primary anthracycline resistance (n = 32), secondary anthracycline resistance (n = 7), anthracycline pretreatment (n = 22) or no anthracycline pretreatment (n = 8). RESULTS: Among 68 evaluable patients, we observed 6 (9%) complete responses and 27 (40%) partial responses, for an overall response rate of 49% (95% confidence interval 37-61%); the disease remained stable in 17 patients (25%). Responses according to the above subgroups were as follows: primary anthracycline resistance 41%, secondary anthracycline resistance 43%, anthracycline pretreatment 64% and no anthracycline pretreatment 43%. The median time to response, median time to progression and median overall survival were 2, 7 and 10 months, respectively. Myelosuppression was the dose-limiting toxicity, with grade 4 neutropenia occurring in 47% of the patients and neutropenic fever in 12%. G-CSF was added in the case of grade 4 febrile neutropenia; a 25% reduction in the dose of docetaxel was required in 4 patients. Other side effects were mild. CONCLUSIONS: The results of the present trial confirm the high activity of docetaxel in heavily pretreated patients with advanced breast cancer, including those with strictly defined anthracycline resistance.     

吉西他滨联合顺铂治疗三阴性晚期乳腺癌的临床观察

目的:观察吉西他滨联合顺铂方案治疗对蒽环类和紫杉类耐药的晚期三阴性乳腺癌的近期疗效和不良反应。方法:32例对蒽环类和紫杉类耐药的晚期乳腺癌患者,经免疫组化证实ER、PR、HER-2均阴性,给予吉西他滨联合顺铂方案治疗,具体用药为:吉西他滨1000mg/m2静脉滴注,第1、8天;顺铂25mg/m2静脉滴注,第1-3天。21天为1周期,至少2个周期。每周期评价不良反应,每2周期后评价疗效,并随访观察肿瘤进展时间。结果:32例患者均可评价疗效与不良反应,获完全缓解(CR)1例(3.1%),部分缓解(PR)10例 (31.2%),稳定(SD)12例(37.5%),进展(PD)9例(28.1%),总有效率(CR+PR)为34.4%（11/32）;中位疾病进展时间为5.2个月。主要不良反应包括骨髓抑制和胃肠道反应,Ⅲ-Ⅳ级中性粒细胞减少及血小板减少发生率分别为33.3%和19.0%,无化疗相关性死亡。结论:吉西他滨联合顺铂方案对蒽环类和紫杉类耐药的晚期三阴性乳腺癌有较好的近期疗效,不良反应可耐受,安全性好。     

Randomized,multicenter, phase II study of gemcitabine plus cisplatin versus gemcitabine plus carboplatin in patients with advanced non-small cell lung cancer

BACKGROUND: We conducted a phase II randomized study to assess the efficacy, with response as the primary endpoint, and the toxicity of gemcitabine/cisplatin (GP) and gemcitabine/carboplatin (GC) in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Patients were randomized to GP (gemcitabine 1200 mg/m(2), days 1 and 8 plus cisplatin 80 mg/m(2) day 2) or GC (gemcitabine 1200 mg/m(2), days 1 and 8 plus carboplatin AUC=5 day 2). Cycles were repeated every 3 weeks. RESULTS: Sixty-two patients were randomized to GP and 58 to GC. A total of 533 cycles were delivered (264 GP, 269 GC), with a median of four cycles/patient. The objective response rate was 41.9% (95% C.I., 29.6-54.2%) for GP and 31.0% (95% C.I., 18.2-42.8%) for GC (P=0.29). No significant differences between arms were observed in median survival (10.4 months GP, 10.8 months GC) and median time to progression (5.4 months GP, 5.1 months GC). Both regimens were very well tolerated with no statistical differences between arms in grade 3/4 toxicities. When all toxicity grades were combined, emesis, neuropathy and renal toxicity occurred more frequently on the GP arm (P<0.005). CONCLUSIONS: GC arm did not provide a significant difference in response rate compared with GP arm, with better overall tolerability. Carboplatin could be a valid alternative to cisplatin in the palliative setting.     

Carboplatin plus gemcitabine repeating doublet therapy in recurrent breast cancer

PurposeThe combination of cisplatin plus gemcitabine is active in metastatic breast cancer. Carboplatin plus gemcitabine, widely used in ovarian and non–small-cell lung cancers, has also been used in breast cancer. This trial examined the efficacy and toxicity of split-dose carboplatin plus gemcitabine in advanced breast cancer.Patients and MethodsPatients with measurable disease, recurrent after adjuvant and ≤ 1 previous treatment for systemic disease, received carboplatin area under the curve = 2.0 (Calvert) plus gemcitabine 800 mg/m², both drugs administered days 1 and 8 every 21 days. Of 15 patients accrued, 13 are fully evaluable.ResultsThere were 2 complete (13.3%) and 6 partial (40%) responses, for an overall response rate by intention to treat of 53.3% (95% CI, 28%-82%). The median time to progression was 4.5 months (95% CI, 2.03-6.97 months), and median overall survival was 28.8 months (95% CI, 9.4-48.2 months). There were 2 patients with grade 3 (13.3%) anemia, 7 patients with grade 3 (46.6%) and 4 patients (26.6%) with grade 4 neutropenia, 4 patients with grade 3 (26.6%) and 3 patients (20%) with grade 4 thrombocytopenia.ConclusionThe repeating doublet of split-dose carboplatin plus gemcitabine reveals activity comparable to that of cisplatin plus gemcitabine, is well tolerated, and warrants evaluation in patients with recurrent breast cancer.     

Gemcitabine plus cisplatin vs. gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial

PURPOSE: This randomized, multicenter, phase III trial was conducted to compare the tolerability of gemcitabine plus cisplatin (GP) vs. gemcitabine plus carboplatin (GC) in chemonaive patients with stage IIIb and IV non-small cell lung carcinoma (NSCLC). Secondary objectives were to evaluate response, duration of response, time to progressive disease (TTPD), and survival. PATIENTS AND METHODS: Eligible patients were required to have stage IIIb or IV NSCLC, no previous chemotherapy, Karnofsky performance status of at least 70, bidimensionally measurable disease, and age 18-75 years. Randomized patients in both arms were given gemcitabine 1200 mg/m(2) on days 1 and 8, followed on day 1 by cisplatin 80 mg/m(2) (GP) or carboplatin AUC=5 (GC). Treatment cycles were repeated every 21 days for a maximum of six cycles, or until disease progression or unacceptable toxicity occurred. RESULTS: Enrolled patients in both arms, 87 in GP and 89 in GC, were well balanced for demographics and disease characteristics. Dose intensity was 93.8 and 92.7% for gemcitabine in GP/GC arms, respectively; 97.7% for cisplatin and 99.9% for carboplatin. Patients with at least one grade 3/4 toxicity excluding nausea, vomiting or alopecia, were 44% in GP arm and 54% in GC arm. The only significantly different toxicities were, nausea and vomiting in GP and thrombocytopenia in GC group. The overall response rates, median TTPD, response duration and survival were, 41/29%, 5.87/4.75 months, 7.48/5.15 months, and 8.75/7.97 months for GP and GC arms, respectively. CONCLUSION: GP and GC are effective and feasible regimens for advanced NSCLC, and are comparable in efficacy and toxicity. GC may offer acceptable option to patients with advanced NSCLC, especially those who are unable to receive cisplatin.     

Randomised, open-label, phase II trial of paclitaxel, gemcitabine and cisplatin versus gemcitabine and cisplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium

The purpose of the study was to evaluate the antitumor activity and the safety of paclitaxel combined with gemcitabine and cisplatin in patients affected by advanced transitional cell carcinoma of the urothelium (TCC). Eighty-five patients affected by advanced TCC and measurable disease were randomized to receive either paclitaxel at dosage of 70 mg/m2, gemcitabine 1000 mg/m2 and cisplatin 35 mg/m2 on days 1 and 8 every 3 weeks (GCP) or gemcitabine 1000 mg/m2 on days 1, 8, 15 and cisplatin 70 mg/m2 on day 2 every 4 weeks (GC). All enrolled patients were considered evaluable for response and toxicity (intention to treat). The observed response rate was 43% for GCP and 44% for GC combination, respectively. Median time to treatment failure was 32 weeks for GCP and 26 weeks for GC and overall survival 61 vs 49 weeks, respectively (p-value not significant). Grade 3-4 neutropenia was observed in 49% of patients treated with GCP vs 35% of those treated with GC (P=0.05) and grade 3-4 thrombocytopenia was observed in 36% of GCP treated patients as compared to 21% of those treated with GC (P=0.01). Seven patients over 70 years old or with poor PS were removed from the study: 6 patients from GCP group (2 toxic deaths, 2 grade 4 myelotoxicity and 2 grade 3 asthenia) and 1 from GC group was lost to follow-up after the first cycle. The combination of paclitaxel, gemcitabine and cisplatin is effective in the treatment of TCC. However, the addition of paclitaxel to the combination of gemcitabine plus cisplatin seems to increase toxicity, therefore it seems not suitable for poor PS patients and those over 70 years old. Larger and more powered studies are needed to exactly define the role of paclitaxel in this combination.     

吉西他滨联合顺铂方案治疗晚期乳腺癌临床研究

[目的]观察吉西他滨联合顺铂方案治疗晚期乳腺癌的近期疗效和毒副反应。[方法]38例晚期乳腺癌患者给予GP方案化疗：吉西他滨1000mg/m2,d1、d8,顺铂30mg/m2,d1～d3,21d为1个周期。每2个周期评价疗效。[结果]38例患者中位治疗周期数为6个周期（2～10个周期）,获CR 3例（7.9%）,PR 13例（34.2%）,SD 10例（26.3%）,PD 12例（31.6%）,总有效率（CR＋PR）为42.1%。主要毒副作用为骨髓抑制和胃肠道反应。Ⅲ度或Ⅲ度以上毒副反应为白细胞下降（36.84%）、中性粒细胞下降（36.84%）、血小板减少（15.79%）、呕吐（13.15%）和贫血（7.89%）。[结论]吉西他滨联合顺铂治疗晚期乳腺癌近期疗效好,毒副反应可以耐受,可作为晚期乳腺癌的治疗选择。     

Phase I/II study of gemcitabine plus mitoxantrone as salvage chemotherapy in metastatic breast cancer

The purpose of this study was to determine the maximum-tolerated dose of gemcitabine plus mitoxantrone in women with metastatic breast cancer (MBC) and to evaluate activity and toxicity of this combination in a phase II trial. Sixty-three patients with MBC, previously treated with chemotherapy including anthracycline and/or taxanes, were treated with mitoxantrone 10 or 12 mg m(-2) intravenously on day 1 plus gemcitabine in escalating doses from 600 to 1200 mg m(-2) intravenously on days 1 and 8, every 3 weeks. In phase I, on 23 patients entered on study, dose-limiting toxicity occurred at the dosage of 1200 mg m(-2) gemcitabine and 10 mg m(-2) mitoxantrone, with three out of five patients developing grade 4 neutropenia. In phase II, with gemcitabine administered at 1000 mg m(-2) and mitoxantrone at 10 mg m(-2), 12 (30%) out of 40 assessable patients responded, even if no complete response was obtained. Moreover, stable disease was observed in eight (20%) patients. The median time to treatment failure was 22 weeks (range, 2-33), and median survival was 42 weeks (range, 2-92). Grade 3 and 4 neutropenia were observed in 12 (30%) and one (2.5%) cases respectively; grade 3 thrombocytopenia was observed in two patients (5%), grade 2 mucositis in two patients (5%), grade 3 anaemia in two patients (5%), grade 3 alopecia in one patient (2.5%) and asymptomatic cardiotoxicity in three patients (8%), respectively. In conclusion, the doses of 10 mg m(-2) (day 1) for mitoxantrone and 1000 mg m(-2) for gemcitabine (days 1-8) every 3 weeks resulted active and safe in MBC. Further investigations in less heavily pretreated patients are warranted.     

吉西他滨联合顺铂治疗蒽环类和（或）紫杉类化疗后晚期乳腺癌疗效观察

目的观察吉西他滨(泽菲)联合顺铂治疗蒽环类和(或)紫杉类化疗后的转移性乳腺癌的疗效和毒副作用。方法蒽环类和(或)紫杉类化疗后的转移性乳腺癌患者29例,采用吉西他滨(泽菲)1000 mg/m2,d1、d8,静滴;顺铂30 mg/m2,d1、d8,静滴,21 d为1个周期。结果29例患者中,CR 1例,PR 11例,SD 9例,PD 8例,客观有效率为41.4%,中位生存期13.2个月,中位肿瘤进展时间5.4个月。毒副作用主要为中性粒细胞和血小板减少。结论吉西他滨联合顺铂治疗蒽环类和(或)紫杉类化疗失败的转移性乳腺癌有效率较高,有生存优势,毒副作用可耐受。     

吉西他滨联合顺铂治疗晚期乳腺癌的临床观察

目的探讨吉西他滨联合顺铂方案治疗一线治疗后失败的晚期乳腺癌的临床疗效和不良反应。方法对入组的32例经病理证实的既往治疗后进展的乳腺癌患者,应用吉西他滨1000mg/m2,静滴,第1天、第8天;顺铂25mg/m2,静滴,第2～4天;联合化疗,每21天为1个周期。至少2个周期后评价疗效。结果 32例患者中,部分缓解(CR)3例(9.4%),完全缓解(PR)15例(46.9%),疾病稳定(SD)9例(28.1%),疾病进展(PD)5例(15.6%),总有效率(CR+PR)56.3%,临床获益率为84.4%。中位疾病进展时间(TTP)8.7个月。1年生存率62.5%。不良反应以骨髓抑制、消化道反应最为常见。结论应用吉西他滨联合顺铂治疗既往化疗后进展的晚期乳腺癌,疗效较好,不良反应较轻,值得临床推广应用。     

Gemcitabine based combination regimens for treatment of refractory advanced breast cancer

Objective:Anthracycline and taxane are the standard agents in combined chemotherapy of advanced breast cancer.However,when these agents based chemotherapy is failure,the selection of salvage regimen is still of problem.Gemcitabine,an active agent in both lung cancer and pancreas cancer,is demonstrated effective in breast caner.But there have been relatively less data of gemcitabine in anthracycline and/or taxane-resistant breast cancer.Therefore we employe this study to explore the efficacy and safety of gemcitabine based combination regimen in this population.Methods:From May 2002 to March 2006,28 patients with measurable lesion of advanced metastatic breast cancer who were resistant to prior anthracycline and taxane based chemotherapy were enrolled.Patients were treated with gemcitabine based combination chemotherapy with a median cycles of 3(range 2-6).Results:The overall response rate was 28.6%(8/28),with 1 CR(Complete response 3.5%)and 7 PRs(Partial response 25%).Stable disease was seen in 8 patients(28.6%)while disease progressed in 12 patiens(42.8%).The median time to progression was 4.5 m(range,2-23 m).The main toxicity included bone marrow depression,alopecia,mucositis and peripheral neurotoxicity.The grade 3 to 4 clinical adverse effect was leukopenia in 5 cases(17.9%)and thrombocytopenia in 8 cases(30%).Conclusion:Gemcitabine based combination regimens is feasible in anthracycline and taxane-resistant advanced breast cancer.The clinical response and TTP is acceptable with limited toxicity pattern.     

Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project.

PURPOSE: To compare gemcitabine and cisplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) chemotherapy in patients with stage IIIB (limited to T4 for pleural effusion and N3 for supraclavicular lymph nodes) or stage IV non-small-cell lung cancer (NSCLC). The end points were the evaluation of quality of life (QoL), response rates, survival, and toxicity. PATIENTS AND METHODS: Three hundred seven patients were randomized to receive either gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin 100 mg/m(2) on day 2, every 28 days, or mitomycin 6 mg/m(2), ifosfamide 3,000 mg/m(2), and mesna on day 1 plus cisplatin 100 mg/m(2) on day 2, every 28 days. The whole-blood cell count was repeated on day 1 in both arms and weekly in the GC arm before each gemcitabine administration. RESULTS: No major differences in changes in QoL were observed between the two treatment arms. The objective response rate was 38% in the GC arm compared with 26% in the MIC arm (P =.029). The median survival time was 8.6 months in the GC arm and 9.6 months in the MIC arm (P =.877, log-rank test). Grade 3 and 4 thrombocytopenia was significantly worse in the GC arm (64% v 28%, P <.001), whereas grade 3 and 4 alopecia was reported more commonly in the MIC arm (39% v 12%, P <. 001). CONCLUSION: We report an increased response rate without changes in QoL and a similar overall survival, time to progression, and time to treatment failure for the GC when compared with the MIC regimen in the treatment of advanced NSCLC.     

吉西他滨联合顺铂治疗晚期膀胱癌54例疗效分析

目的探讨晚期膀胱癌的有效而安全的化疗方案。方法对54例晚期膀胱癌应用吉西他滨联合顺铂（GC）方案化疗,第三周重复,共治疗6个周期。结果54例患者完全缓解（CR）9例,部分缓解（PR）21例,总有效率为55.6%,中位生存期为15.1个月。毒性反应主要为白细胞下降、贫血等,均为轻中度,没有因治疗引起死亡。结论GC方案治疗晚期膀胱癌患者疗效肯定,毒副作用较轻,可作为一线治疗方案。     

Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial.

PURPOSE: To compare the survival benefit obtained with cisplatin plus gemcitabine, a cisplatin-based triplet, and nonplatinum sequential doublets in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Stage IIIB to IV NSCLC patients were randomly assigned to receive cisplatin 100 mg/m2 day 1 plus gemcitabine 1,250 mg/m2 days 1 and 8, every 3 weeks for six cycles (CG); cisplatin 100 mg/m2 day 1 plus gemcitabine 1,000 mg/m2 and vinorelbine 25 mg/m2 days 1 and 8, every 3 weeks for six cycles (CGV); or gemcitabine 1,000 mg/m2 plus vinorelbine 30 mg/m2 days 1 and 8, every 3 weeks for three cycles, followed by vinorelbine 30 mg/m2 days 1 and 8 plus ifosfamide 3 g/m2 day 1, every 3 weeks for three cycles (GV-VI). RESULTS: Five hundred fifty-seven patients were assigned to treatment (182 CG, 188 CGV, 187 GV-VI). Response rates were significantly inferior for the nonplatinum sequential doublet (CG, 42%; CGV, 41%; GV-VI, 27%; CG v GV-VI, P =.003). No differences in median survival or time to progression were observed. Toxicity was higher for the triplet: grade 3 to 4 neutropenia (GC, 32%; CGV, 57%; GV-VI, 27%; P <.05); neutropenic fever (CG, 4%; CGV, 19%; GV-VI, 5%; P <.0001); grade 3 to 4 thrombocytopenia (CG, 19%; CGV, 23%; GV-VI, 3%; P =.0001); and grade 3 to 4 emesis (GC, 22%; GCV, 32%; GV-VI, 6%; P <.0001). CONCLUSION: On the basis of these results, CG remains a standard regimen for first-line treatment of advanced NSCLC.     

Gemcitabine monotherapy as salvage chemotherapy in heavily pretreated metastatic breast cancer

SummaryPurposes We evaluated the efficacy and tolerability of gemcitabine monotherapy in heavily pretreated, breast cancer patients as salvage chemotherapy.Methods A weekly infusion of gemcitabine at 850 mg/m2for 30 min, for 3 of every 4 weeks, was introduced in advanced breast cancer patients who had failed previous doxorubicin and taxane based chemotherapy. There was no dose modification, and the treatment was delayed until the leukopenia was recovered with G-CSF support. The efficacy was evaluated every three cycles and the treatment was continued until either disease progression or 12 cycles.Results Of 41 enrolled patients, 38 were evaluable with a median age of 47. Total 178 cycles of gemcitabine was administered and the relative dose intensity was 89. The toxicity was mild with 12 of grade III neutropenia and 14 of grade III/IV thrombocytopenia without clinical symptoms. The response rate was 20 (8/38), comprising two complete and six partial responses. The median response duration and overall survival were 9 (2–25) and 11 months, respectively. The overall survival of 12 months was better in the third line patients than the 7 months in the fourth line treatment group.Conclusion Gemcitabine monotherapy is effective and safe as salvage treatment in heavily pretreated, breast cancer patients.     

High efficacy of gemcitabine and cisplatin in patients with predominantly anthracycline- and taxane-pretreated metastatic breast cancer

Background: Effective and tolerable regimens are sought specifically in patients who have been pretreated with anthracyclines and taxanes. Gemcitabine and cisplatin demonstrated synergistic activity in vitro and provides a new mechanism of drug interaction. Patients and methods: Previously treated patients with metastatic breast cancer (MBC) were enrolled in a multicentre phase II study. Treatment consisted of gemcitabine (750 mg/m²) and cisplatin (30 mg/m²) given on day 1 and 8 every 3 weeks. Results: Thirty-eight patients were recruited, all of whom had previously received chemotherapy (35 pretreated with taxanes, 33 pretreated with anthracyclines). A median of 5 cycles of the study treatment was delivered. There were 2 complete and 13 partial responses, for an overall response rate of 40% (95% confidence interval: 23–56%). Thirteen patients (35%) had stable disease. Tumour response appeared independent of previously applied chemotherapy. Median time-to-progression was 6 months and median overall survival was 13.5 months. Main toxicities were leucopenia and thrombocytopenia (grade 3/4 in 26 and 16% of cycles, respectively). Non-haematological toxicity was rarely severe. Conclusions: Combination chemotherapy with gemcitabine and cisplatin given on 2 out of 3 weeks is well tolerated and active in heavily pretreated patients with MBC, even after prior exposure to anthracyclines and taxanes. V. Heinemann, H.J. Stemmler contributed equally     

健择合并顺铂治疗晚期复治恶性肿瘤25例报告

目的 探讨健择合并顺铂对复治的局部晚期复发或转移性恶性肿瘤的疗效和毒性反应。方法 使用健择（1000mg/m^2,iv,第1、8、15天）加顺铂（50mg,iv,第15－17天）联合化疗两个周期（28天为一个周期）,治疗25例复治的晚期复发或转移恶性肿瘤患者。结果 可评价的患者20例,无CR患者,PR5例（25％）、NC9例（45％）,PD6例（30％）,总缓解率25％。本研究主要毒性反应为轻到中度骨髓抑制,其它毒副反应少见。结率 健择合并顺铂对复治的部分晚期恶性肿瘤有一定疗效,毒性反应可以耐受,可在临床推广使用。     

吉西他滨联合顺铂治疗晚期乳腺癌的疗效评价

目的：观察吉西他滨联合顺铂治疗一线解救治疗失败的晚期转移性乳腺癌的疗效及毒副反应。方法：吉西他滨1250mg／m2加入生理盐水100ml 快速静滴 d1、8;顺铂75mg／m2加入250ml 生理盐水静滴 d1,每个周期21天,至少2个周期。结果：37例患者均评价疗效。总有效率（ORR）为59．46％,其中完全缓解（CR）1例,部分缓解（PR）21例,疾病稳定（SD）6例,疾病进展（PD）9例。主要毒副反应为骨髓抑制（Ⅱ－Ⅲ度）和消化道反应（Ⅱ－Ⅲ度）。结论：吉西他滨联合顺铂治疗晚期乳腺癌有较好疗效,且对蒽环类和／或紫杉类药物治疗失败的患者亦有较好疗效,毒副反应可耐受,可作为治疗复发转移乳腺癌的解救治疗方案。     

Clinical effect of irinotecan in advanced and metastatic breast cancer patients previously treated with doxorubicin- and docetaxel-containing regimens

BACKGROUND: Previous phase II trials in Japan suggested that irinotecan was a promising agent for advanced or metastatic breast cancer pretreated with anthracycline. However, irinotecan has not yet been evaluated in the salvage setting for breast cancer pretreated with both anthracycline and taxane, which are two active agents for breast cancer. METHODS: The efficacy and safety of irinotecan were retrospectively evaluated in patients with breast cancer who had previously been treated with both doxorubicin and docetaxel. From 1996 to 1999, irinotecan was administered to 20 patients, all with a performance status of <2. Irinotecan treatment was repeated in approximately 6 week cycles consisting of the administration of irinotecan once weekly for 4 weeks followed by a 2 week rest. The median dose of irinotecan administered was 100 mg/m(2) weekly. The median number of irinotecan cycles given was 1 (range: 1-8 cycles). The median total dose was 388 mg/m(2) (range: 50-2400 mg/m(2)). RESULTS: Performance status declined to >3 after treatment with irinotecan in four patients. Two patients had grade 3 leukopenia; three had grade 3 anemia and one had a creatinine elevation of grade 4. The objective response rate for all patients was 5.0% (95% CI: 0-15.5%). The median time to progression and overall survival were 35 days (range: 17-285 days) and 124 days (range: 17-667 days), respectively, since the start of the administration of irinotecan. CONCLUSIONS: Salvage chemotherapy with irinotecan may be inactive against advanced and metastatic breast cancer pretreated with doxorubicin and docetaxel. We will evaluate irinotecan for advanced and metastatic breast cancer patients as first- or second-line chemotherapy combined with anthracycline or taxane.     

多西他赛联合顺铂治疗蒽环类耐药的晚期三阴性乳腺癌的临床观察

目的观察多西他赛联合顺铂治疗蒽环类耐药的晚期三阴性乳腺癌的疗效及安全性。方法 18例蒽环类耐药的晚期三阴性乳腺癌患者给予多西他赛75 mg·m-2,静滴,d1;顺铂25 mg·m-2,静滴,d1～3,3周重复,治疗后评价客观疗效及毒副反应。结果 18例患者均可评价疗效,PR 7例(38.9%),SD 8例(44.4%),PD 3例(16.7%),总有效率为38.9%。中位疾病进展时间为6.5个月。毒副反应主要为骨髓抑制和胃肠道反应。结论多西他赛联合顺铂方案治疗蒽环类耐药的晚期三阴性乳腺癌疗效确切,安全性较好。