多西紫杉醇联合顺铂治疗蒽环类耐药的晚期乳腺癌

Objective： To observe the effect and toxicity of docetaxel with cisplatin in anthracyclines-resistant advanced breast cancer. Methods： Forty-five female patients received docetaxel 60 mg/m^2 on dl and cisplatin 30 mg/m^2 on d1-d3 of every 28 days. Every patient was treated with at least 2 cycles and a median of 3 cycles （2-6 cycles ）. Results： Five patients achieved complete response （11.1%） and 18 partial response （40.0%）, 10 stable disease （22.2%）. The overall response rate was 51.1%. The clinical disease control rate was 73.3%, median time to tumor progression （TTP） was 7.8 months （1.0-34.5 months）, median survival time was 17.6 months （range 1.9-48.0 months）, and one year survival rate was 65.2%. The main side effect was marrow suppression. The treatment was well tolerated with grades Ⅲ and Ⅳ leukopenia in nine （20%） and ten （22.2%） patients. Conclusion： Combinative chemotherapy of docetaxel and cisplatin has a good anti-tumor activity on refractory advanced breast cancer with manageable toxicity.     

两组解救方案治疗蒽环类耐药的晚期乳腺癌疗效观察

目的:比较两组化疗方案作为晚期乳腺癌蒽环类耐药患者的解救治疗疗效及不良反应.方法:采用多西紫杉醇(DXL) 顺铂(DDP)、长春瑞滨(NVB) 顺铂方案治疗蒽环类耐药的晚期乳腺癌64例,比较患者的近期有效率、不良反应、疾病进展时间及1年生存率.DXL DDP方案:DXL 60mg/m2,持续1小时静脉滴注,d1;DDP 30mg/m2d2～4.NVB DDP方案:NVB 25mg/m2d1,8;DDP 30mg/m2,d2～4,上述两个方案每3周为一个周期.结果:DXL DDP方案的总有效率为52.9%(18/34),其中CR 5.9%(2/34),PR 47.1%(16/34);中位疾病进展时间(TTP)8个月;中位生存时间18个月,1年生存率62.9%.NVB DDP方案的总有效率为43.3%(13/30),其中CR 3.3%(1/30),PR 40.0%(12/30);中位TTP 7个月;中位生存时间15个月,1年生存率54.8%.两组方案的主要不良反应为骨髓抑制及胃肠道反应.结论:两组方案对于蒽环类耐药的晚期乳腺癌患者均有较好疗效,不良反应可耐受,其近期疗效无明显差异.     

Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: New effective chemotherapy is needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC. PATIENTS AND METHODS: Between January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin (100 mg/m(2)) or a combination of paclitaxel (175 mg/m(2), 3-hour infusion) and cisplatin (80 mg/m(2)) every 21 days. RESULTS: Compared with the cisplatin-only arm, there was a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate for the paclitaxel/cisplatin arm (17% v 26%, respectively; P=.028). Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm, respectively (P=.026). The study, however, failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm, P=.862). There was more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was similar overall between the two arms. CONCLUSION: This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a better clinical response, resulting in an increased time to progression while providing a similar QOL.     

Docetaxel plus gemcitabine or docetaxel plus cisplatin in advanced pancreatic carcinoma: randomized phase II study 40984 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group.

PURPOSE: To define the efficacy and toxicity of docetaxel plus gemcitabine or docetaxel plus cisplatin for advanced pancreatic carcinoma. PATIENTS AND METHODS: Chemotherapy-naive patients with measurable disease and WHO performance status less than 2 were randomly assigned to receive 21-day cycles of gemcitabine 800 mg/m2 on days 1 and 8 plus docetaxel 85 mg/m2 on day 8 (arm A) or docetaxel 75 mg/m2 on day 1 plus cisplatin 75 mg/m2 on day 1 (arm B). Primary end points were tumor response and rate of febrile neutropenia grade. RESULTS: Of 96 randomly assigned patients (49 patients in arm A and 47 patients in arm B), 70 patients were analyzed for response (36 in arm A and 34 in arm B) and 89 patients were analyzed for safety (45 in arm A and 44 in arm B). Confirmed responses were observed in 19.4% (95% CI, 8.2% to 36.0%) of patients in arm A and 23.5% (95% CI, 10.7% to 41.2%) in arm B. In arm A, the median progression-free survival (PFS) was 3.9 months (95% CI, 3.0 to 4.7 months), median survival was 7.4 months (95% CI, 5.6 to 11.0 months), and 1-year survival was 30%. In arm B, the median PFS was 2.8 months (95% CI, 2.6 to 4.6 months), median survival was 7.1 months (95% CI, 4.8 to 8.7 months), and 1-year survival was 16%. Febrile neutropenia occurred in 9% and 16% of patients in arms A and B, respectively. CONCLUSION: Both regimens are well tolerated and show activity in advanced pancreatic carcinoma. The safety profile and survival analyses favor docetaxel plus gemcitabine for further evaluation.     

Randomized phase II trial of two different schedules of docetaxel plus cisplatin as first-line therapy in advanced nonsmall cell lung cancer

BACKGROUND: There is increasing interest in the use of a weekly administration of docetaxel as a way of reducing its hematologic toxicity. The purpose of the current randomized study was to evaluate the toxicity and efficacy of docetaxel plus cisplatin combination on 2 schedules in patients with previously untreated, advanced nonsmall-cell lung cancer (NSCLC). METHODS: Consenting patients with advanced NSCLC were randomized to receive first-line chemotherapy with cisplatin 75 mg/m(2) on Day 1, plus 3-weekly (75 mg/m(2) on Day 1) or weekly (35 mg/m(2) on Days 1, 8, and 15 of a 4-week cycle) docetaxel, for up to 6 cycles. RESULTS: Of 86 patients accrued, 41 patients were treated with 3-weekly and 43 with weekly docetaxel plus cisplatin. The most frequent grade 3/4 toxicity in the 3-weekly arm was neutropenia (56% of patients). In those receiving the weekly regimen, the frequent grade 3/4 toxicities were fatigue (44%) and nausea/vomiting (35%). The overall response rate was 40% with the 3-weekly and 39% with the weekly arm (P = .74). The median progression-free survival was 4.3 months in the 3-weekly arm and 3.9 months in the weekly arm (P = .08) and the median survival was 10.3 and 10.0 months, respectively (P = .76). Quality of life data showed no relevant difference between the arms. CONCLUSIONS: The weekly schedule of docetaxel plus cisplatin combination as first-line chemotherapy for advanced NSCLC, while feasible, has no clear advantage over the standard 3-weekly regimen.     

Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study.

PURPOSE: In randomized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer. Although in nonrandomized trials, carboplatin and paclitaxel was a less toxic and highly active combination regimen, there remained concern regarding its efficacy in patients with small-volume, resected, stage III disease. Thus, we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population. PATIENTS AND METHODS: Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were randomly assigned to receive cisplatin 75 mg/m2 plus a 24-hour infusion of paclitaxel 135 mg/m2 (arm I), or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m2 over 3 hours (arm II). RESULTS: Seven hundred ninety-two eligible patients were enrolled onto the study. Prognostic factors were similar in the two treatment groups. Gastrointestinal, renal, and metabolic toxicity, as well as grade 4 leukopenia, were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II. Neurologic toxicity was similar in both regimens. Median progression-free survival and overall survival were 19.4 and 48.7 months, respectively, for arm I compared with 20.7 and 57.4 months, respectively, for arm II. The relative risk (RR) of progression for the carboplatin plus paclitaxel group was 0.88 (95% confidence interval [CI], 0.75 to 1.03) and the RR of death was 0.84 (95% CI, 0.70 to 1.02). CONCLUSION: In patients with advanced ovarian cancer, a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity, is easier to administer, and is not inferior, when compared with cisplatin plus paclitaxel.     

Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732.

PURPOSE: To determine, in a randomized comparison, whether the addition of paclitaxel to etoposide and cisplatin improves the time to progression and overall survival in patients with extensive small-cell lung cancer (SCLC) compared with standard etoposide and cisplatin and to compare the regimens' toxicity. PATIENTS AND METHODS: Eligible patients (N=587) with untreated extensive SCLC were randomly assigned to receive either cisplatin 80 mg/m2 on day 1 and etoposide 80 mg/m2 on days 1 through 3 administered every 3 weeks for six cycles (EP) or cisplatin 80 mg/m2 on day 1, paclitaxel 175 mg/m2 over 4 hours on day 1, and etoposide 80 mg/m2 on days 1 to 3 followed by recombinant human granulocyte colony-stimulating factor on days 4 to 18 administered every 3 weeks for six cycles (PET). RESULTS: Reporting of demographics, response, and survival included 565 patients, of whom 282 were randomly assigned to receive EP and 283 were assigned to receive PET. Overall response rates were 68% for the EP arm and 75% for the PET arm. Median failure-free survival time was 5.9 months for the EP arm and 6 months for the PET arm (P = .179). Median overall survival time was 9.9 months for patients on EP and 10.6 months for patients on PET (P = .169). Toxic deaths occurred in 2.4% of the patients on EP and 6.5% of patients on PET. CONCLUSION: PET did not improve the time to progression or survival in patients with extensive SCLC compared with EP alone and was associated with unacceptable toxicity.     

A phase II study of paclitaxel/cisplatin combination in patients with metastatic breast cancer refractory to anthracycline-based chemotherapy

AIMS AND BACKGROUND: To investigate the safety and efficacy of a paclitaxel and cisplatin regimen in a selected group of metastatic breast cancer patients with primary or acquired chemo-resistance to anthracycline-based chemotherapy. PATIENTS AND METHODS: Thirty-eight consecutive women with metastatic breast cancer (PS < or =2) were entered in this phase II trial; all patients had been previously treated for metastatic disease with chemotherapy containing anthracyclines and had shown a progression of the disease during drug administration or after a clinical response lasting less than 6 months. Fifteen patients had received 2 or more chemotherapeutic regimens for advanced disease; 31 patients had > or =2 sites of metastatic disease. Paclitaxel (135 mg/m2) was administered iv by a 3-hr infusion followed by iv infusion of cisplatin (75 mg/m2) on day 1, every 3 weeks for 6 cycles. After the completion of the planned chemotherapy administration, 9 responsive patients continued to receive paclitaxel alone (175 mg/m2) iv, on day 1, every 3 weeks, until disease progression or unacceptable toxicity. RESULTS: A partial clinical response was recorded in 17 cases (45%; 95% CI, 30-64%). The median duration of overall response was 8 months; for the 9 responsive patients who continued treatment with paclitaxel alone, 4 had maintained the partial clinical response at the median follow-up of 24 months from the onset of therapy. The median time to progression was 6 months and median overall survival 8 months. Neurotoxicity was the most frequent adverse effect and caused treatment discontinuation in 5 cases for grade 3-4 paresthesia and/or an arthralgia/myalgia syndrome. Grade 3-4 neutropenia occurred in 16 patients (44%). CONCLUSIONS: Paclitaxel/cisplatin is an active regimen for the treatment of patients with metastatic breast cancer refractory to anthracycline-based chemotherapy. However, the cumulative neurotoxicity should limit the efficacy of prolonged paclitaxel monotherapy in responsive patients.     

泰索帝联合顺铂治疗蒽环类药物耐药的晚期乳腺癌的临床研究

目的研究泰索帝联合顺铂治疗蒽环类药物耐药的晚期乳腺癌的疗效和安全性。方法28例蒽环类药物治疗失败的晚期乳腺癌患者均接受泰索帝联合顺铂方案治疗泰索帝75mg/m2静滴,第1天;顺铂80mg/m2静滴,第1天或分3天给予;每3周重复,完成3个周期化疗后评价疗效,有效病例4周后确认。结果28例患者均可评价疗效,CR3例,PR13例,SD11例,PD1例,总有效率(CR PR)57.1%(16/28)。主要不良反应为骨髓抑制。结论泰索帝联合顺铂是治疗蒽环类药物耐药的晚期乳腺癌的有效化疗方案,不良反应能够耐受。     

Induction Docetaxel and Cisplatin Followed by Weekly Docetaxel and Cisplatin with Concurrent Radiotherapy in Locally Advanced Stage III Non Small Cell Lung Cancer (LA-NSCLC)-A Phase II Study

Purpose: The objective of this phase II study was to document the activity and to evaluate the toxicity of docetaxel and cisplatin as induction chemotherapy followed by concurrent docetaxel and cisplatin with thoracic radiation in locally advanced stage III non small cell lung cancer. Patients and Methods: Twenty-seven patients with stage III locally advanced non-small cell lung cancer received induction chemotherapy with two cycles of docetaxel 75mg/m2 and cisplatin 75mg/m2 D1 every 3 weeks. Patients without disease progress after induction chemotherapy were assigned to concurrent chemoradiotherapy 20mg/m2 docetaxel&25mg/m2 cisplatin administrated on day 1 every week for 6 weeks along with concurrent radiotherapy at a dose of 60Gy in 30 fractions (2 Gy/fraction and 5 fractions per week). The primary endpoint was to determine the overall response rate (ORR), the secondary endpoint was to evaluate time to progression (TTP) and safety profile. Results: After induction chemotherapy, the overall response rate (ORR) was 44.4%, 23 patients without disease progress were assigned to concurrent treatment with an overall response rate of 65%. Median survival time was 17 months, time to progression was 11.5 months and the one-year survival was 58%. Neutropenia was the most common toxicity during induction therapy (26% expressed grade 3-4) whereas esophagitis was the most common toxicity during concurrent phase (17.3% expressed grade 3-4); toxicities were manageable. Conclusion: Induction chemotherapy by docetaxel and cisplatin followed by weekly docetaxel and cisplatin with concurrent thoracic radiation therapy is feasible and tolerable. These results warrant further large randomized studies to document and confirm the effectiveness of this regimen. Key Words: Lung cancer , Docetaxel , Cisplatin , Concurrent chemoradiotherapy.     

紫杉醇脂质体联合顺铂方案一线治疗晚期非小细胞肺癌的临床随机对照研究

背景与目的紫杉醇联合顺铂方案(pacilitaxel plus cisplatin,TP)是目前一线治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的标准方案之一。本研究旨在比较紫杉醇脂质体联合顺铂(liposome pacilitaxelplus cisplatin,LP)方案与TP方案一线治疗晚期NSCLC的近期疗效、远期生存及毒副反应。方法 100例患者随机分为两组,分别静脉注射紫杉醇脂质体和紫杉醇注射液150 mg/m~2,第1天,联合顺铂75mg/m~2,第1天-2天,21天一个周期。结果 100例患者均可评价疗效,其中LP组中位无进展生存期(progression free survival,PFS)为5.1个月,中位总生存期(overall survival,OS)为9.0个月,客观反应率(response rate,RR)为26%;TP组中位PFS为4.2个月,中位OS为9.3个月,RR为24%;两组比较均无统计学差异(P=0.110;P=0.342;P=0.890)。两组Ⅲ度+Ⅳ度毒性反应均无统计学差异(P>0.05),LP组末梢神经炎发生率低于TP组(8%vs 28%,P=0.030)。结论 LP方案一线治疗晚期NSCLC疗效与TP方案相当,末梢神经炎发生率低于TP方案。     

泰索帝联合顺铂治疗蒽环类耐药性晚期乳腺癌28例

目的 观察泰索帝联合顺铂治疗蒽环类耐药性晚期转移性乳腺癌28例的疗效与毒副反应.方法 泰索帝75 mg/m2,静滴,d1;顺铂75 mg/m2,静滴,d2-4,同时给与水化、利尿、止吐以及抗过敏预处理等治疗,21 d为1周期.中位化疗周期数为3个(2～5个)周期.结果 28例均可评价疗效.完全缓解(CR)2例(7.1%),部分缓解(PR)13例(46.4%),稳定(SD)6例(21.4%),进展(PD)7例(25%),总有效(CR PR)15例(53.6%),中位肿瘤进展时间(TTP)5.6个月,1年生存率63.7%.主要毒副反应为骨髓抑制、恶心、呕吐.结论 泰索帝和顺铂联合治疗蒽环类耐药的晚期转移性乳腺癌疗效较好,毒副反应轻,耐受性较好,是蒽环类耐药性乳腺癌的有效治疗方案.     

周剂量多西紫杉醇联合顺铂和5-氟尿嘧啶治疗晚期胃癌

  目的 观察周剂量多西紫杉醇联合顺铂（DDP）、5-氟尿嘧啶（5-Fu）治疗晚期胃癌的临床疗效和毒副作用。方法 晚期胃癌患者28例，给予多西紫杉醇35 mg／m2，静脉滴注1 h，第1、8、15天；DDP 75 mg／m2，均分第1 ~ 3天静脉滴注，5-Fu 500 mg／m2，24 h中心静脉置泵持续滴注，第1 ~ 5天，28 d为1个周期。化疗2 ~ 6个周期后按WHO实体瘤疗效评价标准（RECIST）评定疗效，按WHO标准评价不良反应。结果 全组28例均可评价疗效，其中完全缓解（CR）2例，部分缓解（PR）13例，稳定（SD）7例，近期客观有效率53.4 %，中位疾病进展时间（TTP）为8.7个月，中位生存期（MS）为11.8个月，1年生存率为47.8 %。主要不良反应为骨髓抑制和胃肠道反应。但Ⅲ ~ Ⅳ度发生率较低。结论 周剂量多西紫杉醇联合DDP和5-Fu治疗晚期胃癌疗效较好，患者毒副作用轻，耐受性好，值得进一步推广使用。     

Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer.

PURPOSE: This randomized, controlled, multicenter, open-label, phase III study compared docetaxel versus paclitaxel in patients with advanced breast cancer that had progressed after an anthracycline-containing chemotherapy regimen. PATIENTS AND METHODS: Patients (n = 449) were randomly assigned to receive either docetaxel 100 mg/m2 (n = 225) or paclitaxel 175 mg/m2 (n = 224) on day 1, every 21 days until tumor progression, unacceptable toxicity, or withdrawal of consent. RESULTS: In the intent-to-treat population, both the median overall survival (OS, 15.4 v 12.7 months; hazard ratio [HR], 1.41; 95% CI, 1.15 to 1.73; P = .03) and the median time to progression (TTP, 5.7 months v 3.6 months; HR, 1.64; 95% CI, 1.33 to 2.02; P < .0001) for docetaxel were significantly longer than for paclitaxel, and the overall response rate (ORR, 32% v 25%; P = .10) was higher for docetaxel. These results were confirmed by multivariate analyses. The incidence of treatment-related hematologic and nonhematologic toxicities was greater for docetaxel than for paclitaxel; however, quality-of-life scores were not statistically different between treatment groups over time. CONCLUSION: Docetaxel was superior to paclitaxel in terms of OS and TTP. ORR was higher for docetaxel. Hematologic and nonhematologic toxicities occurred more frequently in the docetaxel group. The global quality-of-life scores were similar for both agents over time.     

顺铂联合多西他赛与联合紫杉醇对晚期宫颈癌的疗效比较

目的 对比分析顺铂联合多西他赛与联合紫杉醇对晚期宫颈癌的临床治疗效果.方法 选择晚期宫颈癌患者78例,随机分为2组.多西他赛组患者给予顺铂50 mg/m2联合多西他赛75 mg/m2进行治疗,紫杉醇组患者给予顺铂50 mg/m2联合紫杉醇60 mg/m2进行治疗,比较2组的临床治疗效果和不良反应发生情况.结果 多西他赛组的有效率为81.08%(31/37),紫杉醇组的有效率为78.05%(32/41),2组无明显差异(P>0.05).紫杉醇组消化道症状、严重骨髓抑制以及神经毒性的发生率均明显高于多西他赛组(P<0.05),2组的免疫抑制发生率无明显差异(P>0.05).结论 顺铂联合多西他赛与顺铂联合紫杉醇对晚期宫颈癌的临床治疗效果相当,但顺铂联合多西他赛的不良反应更少,安全性较高,有利于提高患者的用药依从性,改善生活质量,值得应用推广.     

Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial.

BACKGROUND: The combination of paclitaxel with cisplatin or carboplatin has significant activity in non-small-cell lung cancer (NSCLC). This phase III study of chemotherapy-na?ve advanced NSCLC patients was designed to assess whether response rate in patients receiving a paclitaxel/carboplatin combination was similar to that in patients receiving a paclitaxel/cisplatin combination. Paclitaxel was given at a dose of 200 mg/m(2) (3-h intravenous infusion) followed by either carboplatin at an AUC of 6 or cisplatin at a dose of 80 mg/m(2), all repeated every 3 weeks. Survival, toxicity and quality of life were also compared. PATIENTS AND METHODS: Patients were randomised to receive one of the two combinations, stratified according to centre, performance status, disease stage and histology. The primary analyses of response rate and survival were carried out on response-evaluable patients. Survival was also analysed for all randomised patients. Toxicity analyses were carried out on all treated patients. RESULTS: A total of 618 patients were randomised. The two treatment arms were well balanced with regard to gender (83% male), age (median 58 years), performance status (83% ECOG 0-1), stage (68% IV, 32% IIIB) and histology (38% squamous cell carcinoma). In the paclitaxel/carboplatin arm, 306 patients received a total of 1311 courses (median four courses, range 1-10 courses) while in the paclitaxel/cisplatin arm, 302 patients received a total of 1321 courses (median four courses, range 1-10 courses). In only 76% of courses, carboplatin was administered as planned at an AUC of 6, while in 96% of courses, cisplatin was given at the planned dose of 80 mg/m(2). The response rate was 25% (70 of 279) in the paclitaxel/carboplatin arm and 28% (80 of 284) in the paclitaxel/cisplatin arm (P = 0.45). Responses were reviewed by an independent radiological committee. For all randomised patients, median survival was 8.5 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm [hazard ratio 1.20, 90% confidence interval (CI) 1.03-1.40]; the 1-year survival rates were 33% and 38%, respectively. On the same dataset, a survival update after 22 months of additional follow-up yielded a median survival of 8.2 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm (hazard ratio 1.22, 90% CI 1.06-1.40; P = 0.019); the 2-year survival rates were 9% and 15%, respectively. Excluding neutropenia and thrombocytopenia, which were more frequent in the paclitaxel/carboplatin arm, and nausea/vomiting and nephrotoxicity, which were more frequent in the paclitaxel/cisplatin arm, the rate of severe toxicities was generally low and comparable between the two arms. Overall quality of life (EORTC QLQ-C30 and LC-13) was also similar between the two arms. CONCLUSIONS: This is the first trial comparing carboplatin and cisplatin in the treatment of advanced NSCLC. Although paclitaxel/carboplatin yielded a similar response rate, the significantly longer median survival obtained with paclitaxel/cisplatin indicates that cisplatin-based chemotherapy should be the first treatment option.     

A phase 1 study of pralatrexate in combination with paclitaxel or docetaxel in patients with advanced solid tumors.

PURPOSE: Pralatrexate is a rationally designed antifolate with greater preclinical antitumor activity than methotrexate. Pralatrexate was synergistic with paclitaxel and with docetaxel in mouse xenograft experiments. This phase 1 study was designed to determine the maximum tolerated dose and toxicity of pralatrexate plus paclitaxel or docetaxel in patients with advanced cancer. EXPERIMENTAL DESIGN: Pralatrexate was administered i.v. every 2 weeks (days 1 and 15) in a 4-week cycle. Depending on the taxane used and dose being tested, the taxane was administered on days 1 and 15; days 2 and 16; or days 1, 8, and 15. In the latter part of the study, patients in the docetaxel arm were treated with vitamin B(12) and folic acid supplementation to mitigate toxicity and allow pralatrexate dose escalation. RESULTS: For the combination of pralatrexate plus paclitaxel without vitamin supplementation, dose-limiting stomatitis and peripheral neuropathy were encountered at the lowest dose levels tested. For pralatrexate plus docetaxel plus vitamin supplementation, pralatrexate 120 mg/m(2) plus docetaxel 35 mg/m(2) administered on the same day every other week was defined as the maximum tolerated dose and schedule, with dose-limiting toxicities at higher dose combinations including stomatitis and asthenia. Significant antitumor activity was observed for this combination in patients with non-small-cell lung cancer. CONCLUSIONS: Pralatrexate (120 mg/m(2)) plus docetaxel (35 mg/m(2)) plus vitamin supplementation is well tolerated with signs of efficacy against non-small-cell lung cancer that merit phase 2 testing.     

Phase III trial comparing paclitaxel poliglumex vs docetaxel in the second-line treatment of non-small-cell lung cancer

Paclitaxel poliglumex (PPX), a macromolecule drug conjugate linking paclitaxel to polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel. Patients with non-small-cell lung cancer (NSCLC) who had received one prior platinum-based chemotherapy received 175 or 210 mg m(-2) PPX or 75 mg m(-2) docetaxel. The study enrolled 849 previously treated NSCLC patients with advanced disease. Median survival (6.9 months in both arms, hazard ratio=1.09, P=0.257), 1-year survival (PPX=25%, docetaxel=29%, P=0.134), and time to progression (PPX=2 months, docetaxel=2.6 months, P=0.075) were similar between treatment arms. Paclitaxel poliglumex was associated with significantly less grade 3 or 4 neutropenia (P<0.001) and febrile neutropenia (P=0.006). Grade 3 or 4 neuropathy (P<0.001) was more common in the PPX arm. Patients receiving PPX had less alopecia and did not receive routine premedications. More patients discontinued due to adverse events in the PPX arm compared to the docetaxel arm (34 vs 16%, P<0.001). Paclitaxel poliglumex and docetaxel produced similar survival results but had different toxicity profiles. Compared with docetaxel, PPX had less febrile neutropenia and less alopecia, shorter infusion times, and elimination of routine use of medications to prevent hypersensitivity reactions. Paclitaxel poliglumex at a dose of 210 mg m(-2) resulted in increased neurotoxicity compared with docetaxel.     

紫杉醇与多西紫杉醇分别联合顺铂及氟脲嘧啶治疗晚期胃癌的疗效比较

目的比较两种紫杉烷类（紫杉醇、多西紫杉醇）化疗药物分别联合顺铂及氟脲嘧啶治疗晚期胃癌患者的疗效及安全性。方法 48例病理为胃腺癌的Ⅳ期患者,随机分入两组：DCF组25例,TCF组23例。DCF组用药为多西紫杉醇（国产）40mg/m2第1,8天＋氟脲嘧啶500mg/m2第1～5天＋顺铂20mg/m2第1～5天,每三周重复;TCF组用药为紫杉醇（国产）85mg/m2第1,8天＋氟脲嘧啶500mg/m2第1～5天＋顺铂20mg/m2第1～5天,每三周重复。每两周期进行疗效及毒性评价,并进行无疾病进展生存期（PFS）统计。结果 DCF组完全缓解（CR）1例（4.0%）,部分缓解（PR）11例（44.0%）,总有效率48.0%,PFS6.2个月;TCF组CR1例（4.3%）,PR12例（52.2%）,总有效率为56.5%,PFS5.9个月,总有效率、PFS两组差异均无统计学意义。3～4级血液学不良反应：TCF组39.1%,DCF组72.0%,有显著性差异;3～4级非血液学毒性主要为恶心/呕吐,DCF组4例（16.0%）,TCF组5例（21.7%）,差异无统计学意义。其他少见毒性,包括DCF组腹泻1例（4.0%）,TCF组周围神经病变1例（4.3%）。结论紫杉醇与多西紫杉醇联合氟脲嘧啶、顺铂治疗晚期胃癌疗效相近,毒性不尽相同,但均可耐受。     

Efficacy of biweekly paclitaxel therapy in advanced or recurrent breast cancer

To evaluate the feasibility and efficacy of a biweekly schedule of paclitaxel in advanced or recurrent breast cancer, 18 patients were enrolled in this pilot study. Paclitaxel of 120 mg/m2 was administered over 3 hours, and cycles were repeated every two weeks until disease progression or toxicity precluded further treatment. Patients received a median of 10 infusions with actual dose intensity of 55.9 mg/m2/wk, and median time to progression was 4.8 months. The overall response rate was 33.3%, and one patient achieved stable disease for at least 6 months. The responders included patients who received prior anthracycline and/or docetaxel treatment, and the response rate was consistent regardless of metastatic sites. Myelosuppression was the most common toxicity, and a few patients needed G-CSF support, treatment delay or dose reduction because of grade 3 or 4 neutropenia or leukopenia. Although one patient withdrew from this study because of grade 3 sensory disturbance, this regimen was generally well tolerated. A biweekly schedule of paclitaxel seems to be feasible and effective in patients with advanced or recurrent breast cancer.