Dose-dense sequential chemotherapy with epirubicin and paclitaxel versus the combination, as first-line chemotherapy, in advanced breast cancer: a randomized study conducted by the Hellenic Cooperative Oncology Group.

PURPOSE: To compare the efficacy of two different schedules of epirubicin and paclitaxel, as first-line chemotherapy, in patients with advanced breast cancer (ABC). PATIENTS AND METHODS: From October 1997 until May 1999, 183 eligible patients with ABC entered the study. Chemotherapy in group A (93 patients) consisted of four cycles of epirubicin at a dose of 110 mg/m(2) followed by four cycles of paclitaxel at a dose of 225 mg/m(2) in a 3-hour infusion. All cycles were repeated every 2 weeks with granulocyte colony-stimulating factor support. The therapeutic regimen in group B (90 patients) consisted of epirubicin (80 mg/m(2)) immediately followed by paclitaxel (175 mg/m(2) in a 3-hour infusion) every 3 weeks for six cycles. RESULTS: In total, 79 patients (85%) in group A and 72 patients (80%) in group B completed treatment. The median relative dose-intensity of epirubicin was 0.96 in both groups, and that of paclitaxel was 0.96 and 0.97 in groups A and B, respectively. The complete response rate was higher in group A (21.5% v 9% P =.02). Nevertheless, there was no significant difference in the overall response rate between the two groups (55% v 42%, P =.10). Severe neutropenia was more frequently observed with concurrent treatment. After a median follow-up of 16.5 months, median time to progression was 10 months in group A and 8.5 months in group B (P =.27), and median survival was 21.5 and 20 months, respectively (P =.17). CONCLUSION: The present study failed to demonstrate a significant difference in overall response rate between dose-dense sequential administration of epirubicin and paclitaxel compared with the combination of the two drugs given on the same day, even though the sequential treatment resulted in a significantly higher complete response rate.     

Postoperative dose-dense sequential chemotherapy with epirubicin, followed by CMF with or without paclitaxel, in patients with high-risk operable breast cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group.

PURPOSE: The aim of this study was to explore the effect of dose-dense sequential chemotherapy with or without paclitaxel primarily on disease-free survival (DFS) and secondarily on overall survival (OS) in patients with high-risk operable breast cancer. PATIENTS AND METHODS: From June 1997 until November 2000, 604 patients with T1-3N1M0 or T3N0M0 tumors were randomized to three cycles of epirubicin 110 mg/m2 followed by three cycles of paclitaxel 250 mg/m2 followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) (group A), or to four cycles of epirubicin followed by four cycles of CMF, as in group A (group B). All cycles were given every 2 weeks with granulocyte colony-stimulating factor support. RESULTS: A total of 595 patients were eligible. Median follow-up was 61.7 months for group A and 62 months for group B. The 3-year DFS was 80% in group A and 77% in group B. Survival rates were 93% and 90%, respectively. The effect of treatment on the hazard of death was different according to hormonal receptor status. More specifically, in patients with negative receptor status the hazard of death was significantly higher for group B (hazard ratio 2.42). Both regimens were well tolerated and severe acute side-effects were infrequent. No cases of severe cardiotoxicity or acute leukemia were recorded. CONCLUSIONS: The present study failed to demonstrate a significant difference in DFS or OS between the two treatment groups. However, our study has shown clearly that high-dose paclitaxel can be safely incorporated to dose-dense sequential chemotherapy.     

Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase III Trial

To explore the impact of dose intensity (DI) in the adjuvant setting of breast cancer, a randomized phase III trial was conducted comparing postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide, methotrexate and fluorouracil (CMF)in high-risk breast cancer patients. From Oct 2000 to June 2005, 1,121 node-positive patients were randomized to dose-dense sequential epirubicin 110 mg/m(2) and paclitaxel (Taxol, Bristol Myers-Squibb, Princeton, NJ) 250 mg/m(2) (group A), or concurrent epirubicin 83 mg/m(2) and paclitaxel 187 mg/m(2) (group B), both followed by three cycles of "intensified" combination chemotherapy with CMF. By protocol design total cumulative dose and duration of treatment were identical in both groups. Dose intensity of epirubicin and paclitaxel was double in the dose-dense arm. Prophylactic treatment with granulocyte colony-stimulating factor was given with the dose-dense treatments. Disease-free survival (DFS) was the primary endpoint. At a median follow-up of 76 months, 253 patients (23%) had documented disease relapse (123 vs. 130 in groups A and B, respectively) and 208 deaths (101, group A and 107, group B) had been observed. The 5-year DFS rate of 74 and 74% and OS rate of 86 and 85% were observed for group A and group B, respectively. No differences were found in DFS or OS between the two treatment groups (P = 0.78 and P = 0.45 for DFS and OS, respectively). Safety analysis results showing that both regimens were well tolerated and safe have been previously published (Fountzilas et al. Ann Oncol 2008). No DFS or OS benefit from the dose-dense sequential epirubicin and paclitaxel was detected when compared to the concurrent administration of the same drugs. No additional safety issues were raised with long-term follow-up.     

Intra-patient alternated dose escalation of paclitaxel and gemcitabine versus paclitaxel followed by fixed dose rate infusion of gemcitabine in fit elderly non-small cell lung cancer patients. A Southern Italy Cooperative Oncology Group randomised phase II trial

PURPOSE: This study was undertaken to select the best schedule of administration for the paclitaxel plus gemcitabine combination in fit elderly patients affected by locally advanced or metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Ninety-eight patients in stage III or IV NSCLC, aged 70 years or more and in ECOG performance status (PS)相似文献   

Salvage treatment with epirubicin and/or paclitaxel in metastatic breast cancer patients relapsed after high-dose chemotherapy with peripheral blood progenitor cells

AIMS AND BACKGROUND: To evaluate feasibility and efficacy of paclitaxel as a single agent or in combination with epirubicin in breast cancer taxane-naive patients who have failed previous high-dose chemotherapy. METHODS: Since February 1995, we have treated 32 patients in first relapse or progression after high-dose chemotherapy. Nineteen patients had metastatic breast cancer, 12 more than 3 involved axillary lymph nodes, and 1 inflammatory breast cancer at inclusion to the program. The median time to relapse after high-dose chemotherapy was 12 months (range, 2-43). At relapse, 12 patients were treated with epirubicin (90 mg/m2) plus paclitaxel (175 mg/m2) administered on day 1 every 21 days. In 20 patients who had previously received more than 350 mg/m2 of a cumulative dose of epirubicin and in one patient pretreated with chemotherapy containing mitoxantrone, we employed paclitaxel (175 mg/m2) alone. A median number of five courses was administered (range, 2-10). RESULTS: The overall response rate after 3 courses (29 of 32 patients were assessable) was 55% and after 6 courses (21 of 32 patients were assessable) was 57%. The median time to progression was 7 months (95% CI, 5.7-9.2), and median survival was 27.5 months (95% CI, 17.8-37.0). Toxicity was recorded for 180 cycles (epirubicin + paclitaxel for 62 cycles and paclitaxel alone for 118 cycles). The main toxicity in both regimens was hematologic. We observed WHO grade 3-4 neutropenia (in 8 patients, 25%), for which G-CSF (5 microg/kg/day s.c.) was employed. WHO grade 3-4 thrombocytopenia occurred in 2 patients (6%) and WHO grade 3 anemia in 1 patient (3%). CONCLUSIONS: Our study showed that paclitaxel (alone or in combination with epirubicin) is feasible as salvage treatment in heavily pretreated patients.     

Acknowledgement of reviewers 2011

Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin(?)) and paclitaxel (Taxol(?)) alone (ET) or in combination with capecitabine (Xeloda(?), TEX). Starting doses for ET were epirubicin 75?mg/m(2) plus paclitaxel 175?mg/m(2), and for TEX epirubicin 75?mg/m(2), paclitaxel 155?mg/m(2), and capecitabine 825?mg/m(2) BID for 14?days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8?months for patients treated with ET, and 12.4?months for those treated with TEX (HR 0.84, 95% CI 0.65-1.07, P?=?0.16); median OS was 26.0?months for women in the ET versus 29.7?months in the TEX arm (HR 0.84, 95% CI 0.63-1.11, P?=?0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (χ(2) 3.66, P?=?0.16). TTF was significantly longer for patients treated with TEX, 6.0?months, versus 5.2?months following ET (HR 0.73, 95% CI 0.58-0.93, P?=?0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome.     

紫杉醇联合表阿霉素剂量密集辅助化疗的安全性观察

目的 观察紫杉醇(PTX)联合表阿霉素(EPI)剂鼍密集化疗在高复发风险的乳腺癌辅助化疗中的安全性和耐受性.方法 2004年1月至2006年12月共收治101例乳腺癌术后患者,均具有高复发风险.采用FIX联合EPI的方案进行辅助化疗,随机分为密集组和常规组,计划每例患者接受6个周期的化疗.结果 全组有98例患者按计划完成化疗,中位随访24个月,中位无复发生存和总牛存时间均未达到.密集组和常规组的无复发率分别为89.8%和87.8%,2年生存率分别为100%和93.9%,其中高危患者的无复发率分别为86.8%和81.3%,2年生存率分别为100%和90.6%.全组101例患者均可评价不良反应,主要不良反应为粒细胞减少、恶心、呕吐和脱发.密集组和常规组的Ⅲ～Ⅳ度粒细胞减少发生率分别为16.0%和54.9%(P=0.000),凶不良反应而延迟化疗的发生率分别为2.4%和6.0%(P=0.027),两组间其他不良反应差异无统计学意义.结论 PTX联合EPI剂量密集方案用于高复发风险乳腺癌患者的辅助化疗,不良反应可以耐受,是一个安全的、有潜力的方案.     

Feasibility of radiotherapy after high-dose dense chemotherapy with epirubicin, preceded by dexrazoxane, and paclitaxel for patients with high-risk Stage II-III breast cancer

PURPOSE: To verify the feasibility of, and quantify the risk of, pneumonitis from locoregional radiotherapy (RT) after high-dose dense chemotherapy with epirubicin and paclitaxel with peripheral blood progenitor cell support in patients with high-risk Stage II-III breast cancer. METHODS AND MATERIALS: Treatment consisted of a mobilizing course of epirubicin 150 mg/m2, preceded by dexrazoxane (Day 1), paclitaxel 175 mg/m2 (Day 2), and filgrastim; followed by three courses of epirubicin 150 mg/m2, preceded by dexrazoxane (Day 1), paclitaxel 400 mg/m2 (Day 2), and peripheral blood progenitor cell support and filgrastim, every 16-19 days. After chemotherapy, patients were treated with locoregional RT, which included the whole breast or the chest wall, axilla, and supraclavicular area. RESULTS: Overall, 64 of 69 patients were evaluable. The interval between the end of chemotherapy and the initiation of RT was at least 1.5-2 months (mean 2). No treatment-related death was reported. After a median follow-up of 27 months from RT (range 5-77 months), neither clinically relevant radiation pneumonitis nor congestive heart failure had been reported. Minor and transitory lung and cardiac toxicities were observed. CONCLUSION: Sequential high doses of epirubicin, preceded by dexrazoxane, and paclitaxel did not adversely affect the tolerability of locoregional RT in breast cancer patients. The risk of pneumonitis was not affected by the use of sequential paclitaxel with an interval of at least 1.5-2 months between the end of chemotherapy and the initiation of RT. Long-term follow-up is needed to define the risk of cardiotoxicity in these patients.     

Neoadjuvant treatment of locally advanced carcinoma of the uterine cervix with epirubicin, paclitaxel and cisplatin

PURPOSE: The present study was conducted to explore whether neoadjuvant chemotherapy with a combination of epirubicin, paclitaxel and cisplatin could improve the operability and pathological response rate in locally advanced cervical cancer patients. METHODS: Between April 1996 and July 2000, 42 patients with carcinoma of the uterine cervix, FIGO stage Ib(2)-IVa, were treated with two or three 21-day cycles of an epirubicin 100 mg/m(2), paclitaxel 175 mg/m(2), cisplatin 100 mg/m(2) regimen. RESULTS: All patients were eligible for evaluation of toxicity and response. A total of 92 courses of therapy were administered. Three patients had a 20% reduction from the starting dose due to haematological toxicity. Grade 3-4 leukopenia was observed in 15% of cycles, requiring G-CSF support in half of them. Major non-haematological toxicity consisted of grade 3 alopecia (100%), and grade 3 nausea and vomiting (40%). A total of 33 clinical responses (78.5%, 95% CI 63.8-93.2) were recorded, 8 complete responses (CR) and 25 partial responses (PR). Of the 42 patients, 32 (76.2%) underwent radical surgery. At pathological examination 8 complete or microscopic pathological responses, 17 PRs, and 9 patients with stable disease were observed. The median follow-up time was 17 months for the 42 patients enrolled (range 3-62 months). Among the patients submitted to radical surgery, five recurrences were observed, with a median disease-free survival of 47 months. Median overall survival had not been reached at the time of this report. These results appear to be in the range reported for other neoadjuvant cisplatin-based regimens not including paclitaxel. CONCLUSIONS: Neoadjuvant chemotherapy with the epirubicin, paclitaxel and cisplatin combination followed by radical surgery proved to be a safe and effective approach to advanced cervical cancer.     

紫杉醇脂质体与紫杉醇联合表阿霉素在乳腺癌新辅助化疗中的对照研究

目的　比较紫杉醇脂质体与普通紫杉醇联合表阿霉素两种方案在乳腺癌新辅助化疗中的临床疗效和安全性。方法　本试验采用开放式、随机、对照的方法进行研究。５６例需新辅助化疗的女性乳腺癌患者随机分为紫杉醇脂质体联合表阿霉素组（Ａ组）和普通紫杉醇联合表阿霉素组（Ｂ组）。Ａ组每周期予以紫杉醇脂质体１７５ｍｇ／ｍ^２,Ｂ组每周期予以紫杉醇１７５ｍｇ／ｍ^２,每周期两组表阿霉素均为７５ｍｇ／ｍ２。２１天为１周期,每周期评价毒性反应,２周期化疗后评价疗效。结果　入组病例中Ａ组完成２８例,Ｂ组完成２７例。Ａ组和Ｂ组的总有效率（ＣＲ＋ＰＲ）分别为５３.６％和４８.１％（Ｐ＞０.０５）。两组毒副反应中皮疹、皮肤潮红发生率具有明显差异,以Ａ组较低（Ｐ＜０.０５）;其他如血液学毒性、呕吐、腹泻及发热等基本一致（Ｐ＞０.０５）。结论　紫杉醇脂质体与普通紫杉醇联合表阿霉素方案在乳腺癌新辅助化疗中的疗效相当,但紫杉醇脂质体过敏反应发生率明显低于紫杉醇。     

Paclitaxel and gemcitabine vs. paclitaxel and pegylated liposomal doxorubicin in advanced non-nasopharyngeal head and neck cancer. An efficacy and cost analysis randomized study conducted by the Hellenic Cooperative Oncology Group.

BACKGROUND: The prognosis of patients with recurrent and/or metastatic head and neck cancer (HNC) is poor. Median survival of these patients following chemotherapy is in the range of 6 to 9 months. In the present randomized phase III trial we compared two new combinations containing new drugs with proven activity in phase II studies with patients with HNC. PATIENTS AND METHODS: From November 1999 until November 2004, 166 eligible patients with HNC were enrolled in the study. They were treated with paclitaxel 175 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1 and 8 every 3 weeks (group A, 85 patients) or with paclitaxel, as in group A, and pegylated liposomal doxorubicin 40 mg/m(2) on day 1 every 4 weeks (group B, 81 patients). RESULTS: There was no significant difference in response rate (20% versus 29%, P = 0.21), time to disease progression (median; 4.4 months versus 6.0 months, P = 0.09) and survival (median; 8.6 months versus 11.05 months, P = 0.25). Both regimens were generally well tolerated. The most frequently reported side effect, apart from alopecia, was neutropenia. Overall, there was no significant difference in severe toxicity between the two treatment arms. CONCLUSIONS: The present study could not demonstrate a survival benefit with either regimen. Both treatments were well tolerated. Randomized studies comparing each of the two regimens with standard chemotherapy are warranted.     

Sequence effect of epirubicin and paclitaxel treatment on pharmacokinetics and toxicity.

PURPOSE: Sequence-dependent clinical and pharmacokinetic interactions between paclitaxel and doxorubicin have been reported. Some data have shown an influence of paclitaxel on epirubicin metabolism, but no data are available about the effect of diverse sequences of these drugs. We investigated whether reversing the sequence of epirubicin and paclitaxel affects the pattern or degree of toxicity and pharmacokinetics. PATIENTS AND METHODS: Patients receiving epirubicin 90 mg/m(2) by intravenous bolus followed by paclitaxel 175 mg/m(2) over 3-hour infusion or the opposite sequence every 3 weeks for four cycles were eligible. Toxicity was recorded at nadir. Pharmacokinetic data were evaluated at the first and the second cycle and were correlated with toxicity parameters. RESULTS: Thirty-nine consecutive stage II breast cancer patients were treated. Twenty-one patients received epirubicin followed by paclitaxel (ET group), and 18 received the opposite sequence (TE group). No significant difference in nonhematologic toxicity was seen. A lower neutrophil and platelet nadir and a statistically significant slower neutrophil recovery was observed in the TE group. Area under the concentration-time curve (AUC) of epirubicin was higher in the TE group (2,346 ng/mL. h v 1,717 ng/mL. h; P =.002). An inverse linear correlation between epirubicin AUC and neutrophil recovery was also observed (P =.012). No difference was detected in paclitaxel pharmacokinetics. CONCLUSION: Our results support a sequence-dependent effect of paclitaxel over epirubicin pharmacokinetics that is associated with increased myelotoxicity. Because schedule modifications of anthracyclines and paclitaxel can have clinical consequences, the classical way of administration (ie, anthracyclines followed by paclitaxel) should be maintained in clinical practice.     

国产紫杉醇脂质体治疗非小细胞肺癌和乳腺癌的Ⅲ期临床试验报告

目的:比较国产注射用紫杉醇脂质体 顺铂与紫杉醇 顺铂治疗非小细胞肺癌的临床疗效和安全性。比较国产注射用紫杉醇脂质体 表阿霉素和紫杉醇 表阿霉素治疗乳腺癌的临床疗效和安全性。方法:本试验为多中心,开放式,随机,对照研究。分试验组A和对照组B两组。小细胞肺癌:A组注射用紫杉醇脂质体135mg/m2/d1 顺铂75mg/m2/周期,每3周重复;B组注射用紫杉醇135mg/m2/d1 顺铂75mg/m2/周期,每3周重复。乳腺癌:A组注射用紫杉醇脂质体135mg/m2/d1 表阿霉素60mg/m2/d1,每3周重复;B组注射用紫杉醇135mg/m2/d1 表阿霉素60mg/m2/d1,每3周重复。结果:本中心共有21例病人入组,20例病人可评价疗效和不良反应。非小细胞肺癌和乳腺癌各10例。试验组总有效率71.4%(10/14)。对照组总有效率33.3%(2/6),但无显著性差别。主要不良反应为血液学毒性,以白细胞和粒细胞的减少最明显,但统计学上无显著性差异。其它非血液学毒性主要为恶心呕吐,脱发,疲劳和肌肉关节痛,两组无明显差别。结论:国产注射用紫杉醇脂质体是一种安全、有效的药物。     

Dose-dense sequential chemotherapy with epirubicin and paclitaxel in advanced breast cancer

The purpose of this study was to evaluate the activity and toxicity profile of dose-dense sequential chemotherapy with epirubicin (EPI) and paclitaxel in advanced breast cancer (ABC). From January to September 1997, 41 patients with recurrent or metastatic (stage IV) breast cancer were enrolled in the study. Their median age was 57 (range, 33-77) years and median performance status 0 (range, 0-2). Twenty patients had received adjuvant chemotherapy. The chemotherapeutic regimen consisted of 4 cycles of EPI 110 mg/m2 every 2 weeks followed by 4 cycles of paclitaxel, 225 mg/m2 over 3 hours every 2 weeks. G-CSF was administered prophylactically on days 2-10 of each cycle. 34 (83.0%) patients completed all 8 cycles of chemotherapy. A total of 304 cycles were administered, 259 (85.0%) of them at full dose. Thirty (10.0%) cycles were delivered with a delay. The relative median dose intensities of EPI and paclitaxel were 0.95. Most common grade 3-4 side effects were anemia (15.0%) neutropenia (12.0%), thrombocytopenia (5.0%), nausea/vomiting (10.0%), febrile neutropenia (7.5%), and alopecia (90.0%). Overall, 8 (19.5%) patients achieved a complete and 15 (36.5%) a partial response. Median duration of response was 8.4 (range, 3.1-15.5+) months. After a median follow-up of 18.5 months, median time to progression was 8.7 (range, 0.5-21+) months; median survival has not been reached yet. Dose-dense sequential chemotherapy with EPI and paclitaxel shows promising activity as first-line treatment in ABC. Randomized studies comparing this type of chemotherapy with the classical administration of the two drugs together every 3 weeks are ongoing.     

Gemcitabine, epirubicin, and paclitaxel versus fluorouracil, epirubicin, and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: a Central European Cooperative Oncology Group International, multicenter, prospective, randomized phase III trial.

BACKGROUND: The objectives of this phase III trial were to compare the time to progressive disease (TtPD), overall response rate (ORR), overall survival, and toxicity of gemcitabine, epirubicin, and paclitaxel (GET) versus fluorouracil (FU), epirubicin, and cyclophosphamide (FEC) as first-line therapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Female patients aged 18 to 75 years with stage IV and measurable MBC were enrolled and randomly assigned to either gemcitabine (1,000 mg/m(2), days 1 and 4), epirubicin (90 mg/m(2), day 1), and paclitaxel (175 mg/m(2), day 1) or FU (500 mg/m(2), day 1), epirubicin (90 mg/m(2), day 1), and cyclophosphamide (500 mg/m(2), day 1). Both regimens were administered every 21 days for a maximum of eight cycles. RESULTS: Between October 1999 and November 2002, 259 patients (GET, n = 124; FEC, n = 135) were enrolled. Baseline characteristics were well balanced across treatment arms. After a median of 20.4 months of follow-up, median TtPD was 9.1 months and 9.0 months in the GET and FEC arms, respectively (P = .557). The ORR was 62.3% in the GET arm (n = 114) and 51.2% in the FEC arm (n = 129; P = .093). Grade 3 and 4 toxicities, including neutropenia, thrombocytopenia, anemia, stomatitis, neurosensory toxicity, and allergy, occurred significantly more often in the GET arm. CONCLUSION: No significant differences in terms of TtPD and ORR were observed between the two treatment arms. Treatment-related toxicity was higher in the GET arm.     

A phase II trial of paclitaxel and epirubicin in advanced breast cancer

Initial trials of paclitaxel and doxorubicin in advanced breast cancer yielded high response rates but significant cardiac toxicity was observed. In this phase II trial we investigated the efficacy and safety of paclitaxel combined with epirubicin. Patients with advanced breast cancer, performance status 0-2, measurable disease, and a normal left ventricular ejection fraction, who may have received adjuvant chemotherapy were treated with epirubicin 75 mg m(-2) followed by a 3-h infusion of paclitaxel 175 mg m(-2) repeated every 3 weeks. Forty-three eligible patients were treated at six centres. 67% patients received the maximum of six cycles. The response rate was 54% (95% CI 38-69%), 12% CR and 42% PR. Estimated median progression-free survival was 6.9 months (95% CI 5.4-10.0) and estimated median overall survival was 17.9 months (95% CI 14.2-25.7). Four patients had a decrease in the left ventricular ejection fraction (LVEF) of > or =20% of baseline value, and in two patients the LVEF decreased to below the lower limit of normal, but no patient developed clinical evidence of cardiac failure. Grade 4 neutropenia occurred in 56% cycles, but only 4% of cycles were complicated by febrile neutropenia. Grade 3 or 4 non-haematologic toxicity was uncommon. In conclusion, paclitaxel 175 mg m(-2) and epirubicin 75 mg m(-2) is a well tolerated, promising regimen for the treatment of advanced breast cancer.     

Improved survival with single-agent paclitaxel consolidation/maintenance therapy in advanced ovarian carcinoma

OBJECTIVES: Consolidation/maintenance therapy in the standard management of ovarian cancer remains controversial, primarily due to the unknown impact of this strategy on overall survival. METHODS: We examined the survival of a previously reported patient population consecutively treated with either 3 cycles (group A; n = 13 patients) or 12 cycles (group B; n = 13) of single-agent paclitaxel consolidation following 6 cycles of primary induction chemotherapy comprising 6 cycles of carboplatin (AUC = 5), paclitaxel (175 mg/m(2)) and gemcitabine (800 mg/m(2)). RESULTS: There were no differences in the 2 patient populations regarding known relevant prognostic factors (age, stage, tumor grade). The median progression-free survival was 11 months for group A and 24 months for group B (p = 0.0062). The median overall survival in group A was 38 months and was not reached in group B (p = 0.0019). Current follow-up for these 2 patient groups exceeds 43 months. CONCLUSION: We recognize the important limitations of this study, particularly its sample size and nonrandomized nature. However, these data provide support for the conclusion that paclitaxel 'maintenance/consolidation' therapy may favorably impact overall and progression-free survival in advanced ovarian cancer patients who achieve an excellent response to primary platinum-based chemotherapy.     

Paclitaxel, cisplatin, and epirubicin first-line chemotherapy in stage III and IV ovarian carcinoma: long-term results of a phase II study

BACKGROUND: The combination of paclitaxel with cisplatin or carboplatin has become the preferred chemotherapy regimen in the treatment of epithelial ovarian carcinoma. Anthracyclines also have activity in this disease. We conducted a Phase II study by using the combination of paclitaxel, cisplatin, and epirubicin for the treatment of advanced ovarian carcinoma. METHODS: Forty consecutive patients with optimally (n = 7) or suboptimally (n = 33) debulked advanced ovarian carcinoma (International Federation of Gynecology and Obstetrics (FIGO) Stage III or IV) were treated with paclitaxel, 135 mg/m(2), as a 3-hour intravenous infusion, cisplatin 75 mg/m(2) intravenously (i.v.), and epirubicin 50 mg/m(2) i.v. every 3 weeks on an outpatient basis. Granulocyte-colony stimulating factor was administered at a dose of 5 microg/kg/day on Days 5-9. RESULTS: Among 28 patients with measurable disease, 24 (86%%) achieved an objective response including 19 complete and 5 partial responses. Among 18 patients who underwent reassessment laparotomy, pathologic complete response was confirmed in 9 patients. At a minimum follow-up of 40 months, the median overall survival had not been reached whereas the median time to progression for all patients was 18.7 months. The median remission duration for women with measurable disease who responded to treatment was 14 months. The treatment was well tolerated without toxic deaths; the most common toxicity was Grade 3/4 neutropenia that occurred in 30% of patients. Significant neuropathy (Grade 2 or higher) developed in only 8% of patients. CONCLUSIONS: The combination of paclitaxel, cisplatin, and epirubicin is a well tolerated outpatient regimen with significant activity in the treatment of advanced epithelial ovarian carcinoma.     

Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975.

PURPOSE: To compare the therapeutic efficacy of paclitaxel plus cisplatin (arm A) versus gemcitabine plus cisplatin (arm B) and arm A versus paclitaxel plus gemcitabine (arm C) in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC).Materials and METHODS: Patients were randomly assigned to receive either paclitaxel 175 mg/m2 (3-hour infusion, day 1) or gemcitabine 1,250 mg/m2 (days 1 and 8) both combined with cisplatin 80 mg/m2 (day 1) or paclitaxel 175 mg/m2 (3-hour infusion, day 1) combined with gemcitabine 1,250 mg/m2 (days 1 and 8). Primary end point was comparison of overall survival for B versus A and C versus A. Secondary end points included response rate and duration, progression-free survival, toxicities, quality of life [QoL], and cost of treatment. RESULTS: Four hundred eighty patients (arm A, 159; arm B, 160; arm C, 161 patients) were enrolled; all baseline characteristics were balanced. Median survival times were as follows: arm A, 8.1 months; arm B, 8.9 months; arm C, 6.7 months. Response rates were 31.8% for arm A, 36.6% for arm B, and 27.7% for arm C. Other than myelosuppression (B v A, P <.005), no statistically or clinically significant differences were observed for secondary end points. The average treatment costs were 25% higher in arm C as compared with arms A and B. CONCLUSION: Gemcitabine plus cisplatin and paclitaxel plus gemcitabine do not increase overall survival in patients with advanced NSCLC as compared with paclitaxel plus cisplatin. Treatment was well tolerated, and most QoL parameters were similar, but costs associated with the nonplatinum arm were highest.     

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.