High efficacy and low toxicity of weekly docetaxel given as first-line treatment for metastatic breast cancer

BACKGROUND: Docetaxel is one of the most effective antitumor agents currently available for the treatment of metastatic breast cancer (MBC). This phase II multicenter study prospectively analyzed the efficacy and toxicity of docetaxel given on a weekly schedule as first-line treatment of metastatic breast cancer. PATIENTS AND METHODS: All patients received docetaxel, 35 mg/m(2) weekly for 6 weeks, followed by 2 weeks of rest. Subsequent cycles (3 weeks of treatment, 2 weeks of rest) were given until a maximum of 5 cycles or disease progression. Premedication consisted of 8 mg dexamethasone intravenously 30 min prior to the infusion of docetaxel. RESULTS: Fifty-four patients at a median age of 58 years with previously untreated MBC were included in the study. A median of 10 doses (median cumulative dose 339 mg/m(2)) was administered (range: 2-18). The overall response rate was 48.1% (95% CI: 34-61%, intent-to-treat). Median survival was 15.8 months and median time to progression was 5.9 months (intent-to-treat). Hematological toxicity was mild with absence of neutropenia-related complications. Grade 3 neutropenia was observed in 3.7% of patients and grade 3 and 4 anemia was observed in 5.6 and 1.9% of patients, respectively. CONCLUSION: The weekly administration of docetaxel is highly efficient and safe as first-line treatment for MBC and may serve as an important treatment option specifically in elderly patients and patients with a reduced performance status.     

Final results of a phase II clinical trial of weekly docetaxel in combination with capecitabine in anthracycline-pretreated metastatic breast cancer

The addition of capecitabine to docetaxel on a 3-week schedule resulted in superior response rate, increased time to progression (TTP), and improved overall survival in patients with anthracycline-pretreated metastatic breast cancer (MBC). Because the toxicity profile of weekly docetaxel differs from the standard 21-day docetaxel schedule, we performed a phase I/II trial to test the efficacy and safety of weekly docetaxel in combination with capecitabine given for 14 days every 21 days. The phase I study identified the doses of docetaxel (30 mg/m2 weekly) and capecitabine (900 mg/m2 twice daily on days 1-14 every 21 days) used in phase II. Twenty female patients with measurable or assessable MBC were enrolled. Eighteen patients had previously received anthracyclines; 2 had contraindications to anthracyclines. Patients remained on study for a maximum of eight 3-week cycles or until tumor progression or unacceptable toxicity occurred; response assessments were scheduled after cycle 2, 5, and 8. Seventeen patients were assessed after cycle 2; 3 subjects (18%) had a partial response (PR), 9 had stable disease (53%; SD), and 5 patients (29%) had progressive disease (PD). Ten patients were assessable after cycle 5. Two patients (20%) had a PR, 5 patients (50%) had SD, and 3 patients (30%) had PD. The most common grade 3 toxicities were nail loss (45%), asthenia (30%), and hand-foot syndrome (30%), and toxicities led to study discontinuation in 10 patients. The median time to treatment failure was 10 weeks and median TTP was 26 weeks. The median duration of response was 9 weeks and the median duration of SD was 16 weeks. The median overall survival was 82 weeks. This schedule of weekly docetaxel in combination with day 1-14 capecitabine has activity; however, toxicity discourages the use of this schedule in lieu of the standard docetaxel/capecitabine regimen.     

Weekly epirubicin plus lonidamine in advanced breast carcinoma

Lonidamine has been demonstrated to potentiate the cytotoxic activity of several antineoplastic drugs, for example anthracyclines. Moreover, epirubicin is considered one of the most active drugs in advanced breast cancer, although optimal dose and schedule remains to be defined.In the present study we have treated 51 patients with advanced breast cancer with a combination of lonidamine (450mg/day orally from day 1 throughout treatment) and epirubicin (25mg/m² IV) administered according to a weekly schedule for 24 weeks. Objective responses were observed in 29 out of 51 patients (57; CR 16%, PR 41%). Liver metastases responded in eight out of 12 evaluable patients (67%). Average response duration was 12.4 months and median overall survival was 23 months (range 1–90+). Toxicity was negligible.The combination of weekly epirubicin and lonidamine is feasible and active in advanced breast cancer patients.     

低剂量多西紫杉醇单药治疗蒽环类耐药的转移性乳腺癌

目的 评估低剂量强度多西紫杉醇单药每周方案对蒽环类药物耐药且体质较差的转移性乳腺癌患者的疗效和毒性.方法 30例既往接受过蒽环类药物的MBC患者,多西紫杉醇30 ms/m2,静滴,第1、8、15天,每4周重复,最多接受6个周期化疗.结果30例患者中,完全缓解2例,部分缓解9例,有效率为36.7%(95%可信区间为20.5%一53.9%).最常见的毒性反应为血液学毒性.全组平均随访15个月,有效者中位疾病进展时间为(TTP)8.5个月.至随访结束,中位总生存时间(OS)未达到.结论 低剂量强度多西紫杉醇单药每周方案对既往接受过蒽环类药物治疗且体质较差的转移性乳腺癌患者较为有效,且耐受性良好.     

Biweekly docetaxel and vinorelbine in anthracycline-resistant metastatic breast cancer: a multicenter phase II study

The aim of this study was to determine the efficacy and toxicity of a biweekly combination of docetaxel and vinorelbine in patients with metastatic breast cancer (MBC) previously treated with anthracyclines. Eligible patients (n = 49) with MBC received vinorelbine, 25 mg/m2, followed by docetaxel, 60 mg/m2. Cycles were repeated every 14 days for a total of 8 planned cycles. Response rate was evaluated every 4 cycles. All 49 patients were evaluable for safety and 44 for efficacy. Vinorelbine plus docetaxel resulted in an overall response rate of 45% (CI 95%: 31-60) with 2 (4%) complete responses and 18 (41%) partial responses. Patients with visceral metastasis achieved a lower response rate than those without (33% versus 60%, p = 0.044). Time to progression was 11.0 months (CI 95%: 8.6-13.5), and median overall survival was 12.7 months (CI 95%: 9.0-16.4). The most common grade III to IV hematologic adverse events was neutropenia (65% of patients). Febrile neutropenia was observed in 9 cycles (3%) and in 7 patients (14%). Grade III to IV nonhematologic toxicity was rare. Biweekly combination of docetaxel and vinorelbine is an effective and well-tolerated regimen in anthracycline-resistant MBC.     

Weekly Vinorelbine and Docetaxel as Second-Line Chemotherapy for Pretreated Non-Small Cell Lung Cancer Patients: a Phase I-II Trial

Abstract

Docetaxel was proven to be effective as second-line therapy for patients with advanced NSCLC after failure of platinum-based front-line chemotherapy. We designed this phase I/II study to define the Maximum Tolerated Dose of weekly docetaxel combined with weekly vinorelbine, and subsequently evaluate tolerability and activity of this schedule in NSCLC patients who were progressive after treatment with either cisplatin and gemcitabine or carboplatin and paclitaxel regimens. To be eligible for the study, patients were required to have a WHO performance status ≤2, failure after at least two cycles of first platinum-based chemotherapy, and no prior treatment with docetaxel and vinorelbine. A total of 27 patients were enrolled in this phase I/II study. A weekly docetaxel dose of 25 mg/m² was recommended in combination with fixed vinorelbine dose of 20 mg/m², and 24 patients were treated at this dose level. Severe neutropenia (62%) and febrile neutropenia (29%) were the most frequent toxicities, with 83% of patients requiring dose modification or delay. In the phase II study, 5 (21%) patients obtained a partial response, 8 (33%) patients had stable disease, whereas 10 (42%) patients progressed. After a median follow-up of 18.7 months, median survival was 8 months, with 30% surviving at 1 year. Regardless of the use of weekly docetaxel schedule, this regimen was highly myelosuppressive, and did not seem to improve response rate and survival compared to single-agent docetaxel. No further developments of this schedule are warranted.     

A randomised clinical trial of two docetaxel regimens (weekly vs 3 week) in the second-line treatment of non-small-cell lung cancer. The DISTAL 01 study

Docetaxel (75 mg m(-2) 3-weekly) is standard second-line treatment in advanced non-small-cell lung cancer (NSCLC) with significant toxicity. To verify whether a weekly schedule (33.3 mg m(-2) for 6 weeks) improved quality of life (QoL), a phase III study was performed with 220 advanced NSCLC patients, < or =75 years, ECOG PS < or =2. QoL was assessed by EORTC questionnaires and the Daily Diary Card (DDC). No difference was found in global QoL scores at 3 weeks. Pain, cough and hair loss significantly favoured the weekly schedule, while diarrhoea was worse. DDC analysis showed that loss of appetite and overall condition were significantly worse in the 3-week arm in the first week, while nausea and loss of appetite were more severe in the weekly arm in the third week. Response rate and survival were similar, hazard ratio of death in the weekly arm being 1.04 (95% CI 0.77-1.39). A 3-weekly docetaxel was more toxic for leukopenia, neutropenia, febrile neutropenia and hair loss; any grade 3-4 haematologic toxicity was significantly more frequent in the standard arm (25 vs 6%). The weekly schedule could be preferred for patients candidate to receive docetaxel as second-line treatment for advanced NSCLC, because of some QoL advantages, lower toxicity and no evidence of strikingly different effect on survival.     

Weekly docetaxel/paclitaxel in pretreated metastatic breast cancer

The purpose of our study was to evaluate the feasibility and efficacy of weekly docetaxel/paclitaxel in pretreated advanced breast cancer patients. Twenty-six patients with metastatic breast cancer were included in this study. Three different schedules of treatment were administered. The starting schedule, A1, consisted of docetaxel 60 mg/m2 on day 1 plus paclitaxel 60 mg/m2 over 1 hour, weekly for 18 weeks; this schedule was considered feasible if at least 70% of the planned doses were given on time and without reduction. Schedule A2 consisted of the same doses administered on days 1 and 8 every 3 weeks, and schedule B consisted of docetaxel 25 mg/m2 followed by paclitaxel 40 mg/m2 for 1 hour on days 1 and 8 every 3 weeks for a total of 6 cycles. All patients had received prior anthracyclines, and 19 patients were pretreated with taxanes. Seventy-seven percent of patients had received at least 2 prior lines of chemotherapy. Twenty-five patients are assessable for toxicity and efficacy. A total of 109 cycles of chemotherapy have been administered, with a median of 4 cycles per patient (range, 1-8 cycles). The median delivered dose intensity was 27 mg/m2/week for paclitaxel (range, 18-50 mg/m2/week) and 17 mg/m2/week (range, 12-39 mg/m2/week) for docetaxel. Six patients received schedule A1. This schedule was considered not feasible due to neutropenia grade > 2, mucositis, and diarrhea grade 2, which required dose reduction/omission in 33% of administrations. For this reason, treatment in the following 5 patients was omitted on day 15 (schedule A2). Schedule B was found to be more feasible with 16% of dose reductions/omissions. The overall response rate was 68% (95% CI, 50%-86%) with a median duration of response of 10 months (range, 2-18+ months). Treatment was well tolerated; myelosuppression was rare and grade 3 cutaneous toxicity was observed in only 2 patients. In conclusion, weekly docetaxel/paclitaxel is active at low dosages and was well tolerated as salvage chemotherapy in metastatic breast cancer. This regimen represents a valid option as a salvage treatment in taxane- and anthracycline-pretreated patients.     

Phase II study of epirubicin and vinorelbine with granulocyte colony-stimulating factor: A high-activity, dose-dense weekly regimen for advanced breast cancer

Background: This study was designed to explore the effectiveness and tolerability of a weekly regimen of epirubicin and vinorelbine plus granulocyte colony-stimulating factor (G-CSF).Patients and methods: Fifty-two patients with previously untreated advanced breast cancer were treated with epirubicin (25 mg/m²/week) and vinorelbine (25 mg/m²/week) with G-CSF support, for 24 consecutive weeks.Results: The median number of courses per patient was 22 (range 10–24). The administered dose intensity was 23 mg/m² for both epirubicin and vinorelbine. Ten complete responses (19%) and 30 partial responses (58%) were obtained, for an overall response rate of 77%. None of the patients progressed during treatment. The median response duration and time to progression were both 10 months. A total of 1065 courses were assessed for toxicity. Grade 3 neutropenia was the most common toxic manifestation, (39% of patients), without febrile neutropenia or neutropenic sepsis. Two patients had grade 3 cardiac toxicity, which regressed without sequelae. Median survival was 31 months, with a median follow-up of 24 months (range 9–40).Conclusions: Owing to its effectiveness and tolerability, the weekly regimen of epirubicin and vinorelbine plus G-CSF may represent an acceptable alternative for patients with untreated metastatic breast cancer. It could be tested in the adjuvant and neoadjuvant setting.     

Docetaxel plus epirubicin is a highly active, well-tolerated, first-line chemotherapy for metastatic breast cancer: results of a large, multicentre phase II study

Purpose In this multicentre phase II study, the efficacy and safety profile of the combination of docetaxel and epirubicin as first-line chemotherapy for metastatic breast cancer (MBC) were evaluated.Methods Epirubicin (75 mg/m²) and docetaxel (75 mg/m²) were given intravenously once every 3 weeks for six cycles to 133 patients with MBC.Results The overall clinical response rate was 67% (complete and partial responses were 23% and 44%, respectively). The median time to progression was 10.8 months (95% CI 9.7–12.6) and the median overall survival was 19.5 months. Granulocyte colony-stimulating factor support was administered to 32% of patients and in 22% of cycles. Grade 3/4 neutropenia occurred in 35% of patients and febrile neutropenia in 19%. The most frequent grade 3/4 non-haematological toxicities (as percent of patients) were asthenia (6%), vomiting (5%) and nausea (5%). No patients developed congestive heart failure.Conclusions The combination of docetaxel and epirubicin was highly active as first-line treatment for MBC and showed a manageable toxicity profile.     

Weekly etoposide, epirubicin, cisplatin, 5-fluorouracil and leucovorin: an effective chemotherapy in advanced gastric cancer.

In order to optimize the therapeutic index of combining etoposide, epirubicin, cisplatin, 5-fluorouracil (5-FU), leucovorin (EEPFL) chemotherapy in the treatment of advanced gastric cancer, a trial of a novel schedule of weekly administration was conducted. Weekly EEPFL treatment consisted of a concomitant boost of etoposide 40 mg m(-2) i.v. over 30 min, epirubicin 10 mg m(-2) i.v. over 5 min to a backbone regimen, weekly PFL chemotherapy with cisplatin 25 mg m(-2), 5-FU 2200 mg m(-2), leucovorin 120 mg m(-2) given simultaneously by 24-h i.v. infusion. Response, survival and toxicity were evaluated. Forty-two patients were studied. Median age was 69 (range 31-84) years. Twenty-six per cent of patients showed complete response and 45% partial response. The overall response rate was 71% (95% confidence interval 58-84%). For a total of 507 weekly EEPFL cycles delivered, the incidence of grade 4 leucopenia was 1% of cycles. One patient died of neutropenia septicaemia. There was no other grade 4 toxicity. Grade 3 and 2 leucopenia occurred in 7% and 14% of cycles. The incidence of grade 3 and 2 mucositis was 1% and 3% of cycles. Grade 3 and 2 diarrhoea occurred in 0.4% and 1.6% of cycles. Overall median survival was 10 months (range 3-41+ months). Weekly EEPFL chemotherapy is an effective regimen with tolerable toxicities in the treatment of advanced gastric cancer. A randomized controlled clinical trial to formally assess the efficacy and benefit of EEPFL chemotherapy is under way.     

多西紫杉醇联合顺铂每周给药治疗Ⅲ—Ⅳ期NSCLC 30例

目的：观察多西紫杉醇（DOC）联合顺铂（DDP）以每周给药方案治疗Ⅲ－Ⅳ期非小细胞肺癌（NSCLC）的临床疗效,生存期及毒副反应。方法：治疗Ⅲ-Ⅳ期SNCLC患者30例,DOC 25mg/m2静脉点滴1小时,第1,8,15天;DDP 25mg/m2静脉点滴,第1,8,15天,28天为一疗程,至少治疗二周期。结果：总有效率为43＝．4％（13／30）,均为部分缓解,对原发灶和转移灶均有较好疗效,Karnofsky计分增加或不变者占66．7％,中位缓解期为7月,生存年以上者占40％,主要毒副反应为骨髓抑制,Ⅲ-Ⅳ度白细胞下降占16．7％,III度血小板下降占6．7％,无III－IV度血红蛋白下降,非血液学性轻微,结论：DOC与DDP每周给药方案治疗NSCLC有较好疗效,耐受性。     

Phase II trial of weekly docetaxel and gemcitabine for previously untreated, advanced non-small cell lung cancer

Docetaxel and gemcitabine combination chemotherapy has been reported to be active against non-small cell lung cancer (NSCLC) and myelosuppression is the most common dose-limiting toxicity. This prospective phase II study was designed to test the hypothesis that better tolerance and increased dose intensity might be achieved if patients are treated with weekly administration schedule. Thirty-five patients with stage IIIB/IV NSCLC and a performance status 0-2 received first-line chemotherapy with docetaxel 35mg/m2 and gemcitabine 600mg/m2 on days 1, 8 and 15. Treatment was repeated every 4 weeks, for up to 4 cycles. In total, 85 chemotherapy cycles were given (median, 2; range, 1-4). Other than the completion of all 4 planned cycles (n=6), the main reasons for treatment discontinuation were toxicity (n=15) and progressive disease (n=14). The most frequently encountered toxic effects were anemia (52% of patients), nausea and vomiting (60%), fatigue (71%) and anorexia (57%). One patient died of bilateral pneumonitis, which developed shortly after the administration of second cycle. Disease control (objective response and stable disease) in the intent-to-treat (ITT) population was achieved in 60% of patients and the overall response rate was 29% (95% CI, 14-44%). With a median follow-up duration of 13 months, the median progression-free survival and overall survival were 2.8 (95% CI, 0.7-4.8) months and 10.6 (95% CI, 7.0-14.3) months, respectively. In conclusion, weekly schedule of docetaxel and gemcitabine has modest activity with acceptable toxicity profile in advanced NSCLC, but as high frequency of early discontinuation occurred does not merit further study with the present regimen.     

Phase II study of sequential administration of docetaxel followed by doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer.

PURPOSE: To evaluate the feasibility and efficacy of a sequential administration of four cycles of docetaxel (100 mg/m(2) every 3 weeks) followed by four cycles of doxorubicin and cyclophosphamide (AC; 60/600 mg/m(2) every 3 weeks), with subsequent consolidation with docetaxel or AC, as first-line chemotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-eight patients received 443 cycles of chemotherapy (median, 11 cycles/patient; range, 1 to 13 cycles). A total of 267 cycles of docetaxel (60.3%) and 176 of AC (39.7%) were given. Consolidation therapy was given to 33 patients (29 with docetaxel). RESULTS: Grade 4 neutropenia was the most frequent toxicity (83% of patients). This was not cumulative and was rarely complicated by febrile neutropenia or severe infection. The nonhematologic safety profile was favorable: there were no grade 4 adverse events, and grade 3 episodes were infrequent. Docetaxel-specific toxicities were generally not severe. With a median cumulative doxorubicin dose of 397 mg/m(2) (range, 150 to 543 mg/m(2)), two incidences of unrelated congestive heart failure after further treatment with anthracyclines and two of asymptomatic left ventricular ejection fraction decrease were observed. Among the 42 assessable patients, five (12%) had complete and 25 (60%) had partial responses, for an overall response rate of 71% (95% confidence interval, 55% to 84%). Median duration of response was 53 weeks (range, 12 to 72 weeks), and median time to progression was 46 weeks (range, 3 of 72 weeks). With a median follow-up of 40.4 months, median survival was 32 months (range, 2 to 55 months). CONCLUSION: This docetaxel-based sequential schedule is safe and effective in first-line therapy for MBC, without incurring cumulative toxicity, and provides a feasible chemotherapeutic option in this clinical setting.     

Phase I trial of liposomal encapsulated doxorubicin (Myocet; D-99) and weekly docetaxel in advanced breast cancer patients.

BACKGROUND: We conducted a phase I trial to determine the safety and maximum tolerated dose (MTD) of non-pegylated liposome-encapsulated doxorubicin (Myocet; D-99) administered with weekly docetaxel in metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: Twenty-one patients with no prior chemotherapy for MBC received D-99 (60 or 50 mg/m2) intravenously (i.v.) on day 1 and escalating doses of docetaxel (25, 30 and 35 mg/m2 i.v. on days 1 and 8 in cohorts of three to six patients. Treatment cycles were repeated every 21 days for a maximum of six cycles. RESULTS: The maximum tolerated dose (MTD) was 50 mg/m2 of D-99 in combination with 25 mg/m2 of weekly docetaxel. The most common grade 4 toxicity was neutropenia that occurred in 42 (41%) of treatment cycles, with 10 hospitalizations for febrile neutropenia. Serious protocol-defined cardiac events occurred in three (14%) patients, with two (10%; 95% confidence interval [CI] 1% to 30%) developing congestive heart failure (CHF) after a total cumulative anthracycline dose (adjuvant doxorubicin + D-99) of 540 mg/m2. CONCLUSIONS: D-99 in combination with weekly docetaxel, at the doses and schedule as administered in this trial, is not recommended for phase II testing. Additional trials, using different doses and schedules, are required to evaluate the potential side-effects and efficacy of D-99 and docetaxel.     

A phase II randomized study comparing navelbine and capecitabine (Navcap) followed either by Navcap or by weekly docetaxel in the first-line treatment of HER-2/neu negative metastatic breast cancer

Following the proven efficacy and tolerability of Navcap and Navcap followed by docetaxel in the treatment of MBC, a phase II randomized study was initiated to assess the ORR of both arms in the first-line setting of MBC. Patients with no prior chemotherapy for MBC and HER-2/neu negative were eligible. All patients received Navcap (V 25 mg/m2 on d1 and d8 and C 825 mg/m2 bid D1-14 q3w) for a total of 4 cycles. Patients progressing under Navcap were withdrawn and received docetaxel as second-line treatment. Patients responding or stable were randomized to 2 arms: 4 cycles of Navcap (A) or 12 weekly docetaxel (25 mg/m2/week) (B). From July 2004 to July 2008, a total of 106 patients were enrolled. Ninety-four patients were evaluable before randomization, with a clinical benefit of 58%. Twenty-one patients (22%) had disease progression and were therefore not randomized. Forty-one patients were randomized to arm A and 29 patients to arm B. ORRs were 56 and 71% in arms A and B, respectively. The median time to progression and overall survival were 10 and 35 months in arm A and 12 and 37 months in arm B. Adverse events were mild. Arm A: grade 3-4 neutropenia (10%), grade 3 anemia (5%). Arm B: grade 3 neutropenia (6%), grade 3 anemia (6.2%), and grade 2 alopecia (12%). Conclusion: Both Navcap and Navcap followed by Docetaxel regimens were tolerated with manageable toxicity, offering consistent activities in terms of response rate for metastatic breast cancer patients.     

Efficacy and Tolerability of Weekly Docetaxel,Cisplatin, and 5-Fluorouracil for Locally Advanced or Metastatic Gastric Cancer Patients with ECOG Performance Scores of 1 and 2

Background: Docetaxel, cisplatin, 5-fluorouracil (DCF) given every three weeks is an effective, but palliativeregimen and significantly toxic especially in patients who have a low performance score. Here, we aimed to evaluatethe efficacy and tolerability of a weekly formulation of DCF in locally advanced and metastatic gastric cancerpatients. Materials and Methods: 64 gastric cancer patients (13 locally advanced and 51 metastatic) whose ECOG(Eastern Cooperative Oncology Group) performance status (PS) was 1-2 and who were treated with at least twocycles of weekly DCF protocol as first-line treatment were included retrospectively. The weekly DCF protocolincluded 25mg/m2 docetaxel, 25mg/m2 cisplatin, and 24 hours infusion of 750mg/m2 5-fluorouracil, repeated everyweek. Disease and patient characteristics, prognostic factors, treatment response, grade 3-4 toxicity related totreatment, progression free survival (PFS) and overall survival (OS) were evaluated. Results: Of the patients, 41were male and 23 were female; the median age was 63 (29-82) years. Forty-one patients were ECOG-1 and 23were ECOG-2. Of the total, 81.2% received at least three cycles of chemotherapy. Partial response was observedin 28.1% and stabilization in 29.7%. Overall, the disease was controlled in 57.8% whereas progression was notedin 42.2%. The median time to progression was 4 months (95%CI, 2.8-5.2 months) and median overall survivalwas 12 months (95%CI, 9.2-14.8 months). The evaluation of patients for grade 3-4 toxicity revealed that 10.9%had anemia, 7.8% had thrombocytopenia and 10.9% had neutropenia. Non-hematologic toxicity included renaltoxicity (7.8%) and thrombosis (1.6%). Conclusions: In patients with locally advanced or metastatic gastriccancer who were not candidates for DCF administered every-3-weeks, a weekly formulation of DCF demonstratedmodest activity with minimal hematologic toxicity, suggesting that weekly DCF is a reasonable treatment optionfor such patients.     

Phase II study of docetaxel in combination with epirubicin and protracted venous infusion 5-fluorouracil (ETF) in patients with recurrent or metastatic breast cancer. A Yorkshire breast cancer research group study

This study was originally designed as a phase I/II study, with a dose escalation of docetaxel in combination with epirubicin 50 mg m(-2) and 5-fluorouracil (5-FU) 200 mg m(-2) day(-1). However, as dose escalation was not possible, the study is reported as a phase II study of the combination to assess response and toxicity. A total of 51 patients with locally advanced or metastatic breast cancer were treated on this phase II study, with doses of docetaxel 50 mg m(-2), epirubicin 50 mg m(-2) and infusional 5-FU 200 mg m(-2) day(-1) for 21 days. The main toxicity of this combination was neutropenia with 89% of patients having grade 3 and 4 neutropenia, and 39% of patients experiencing febrile neutropenia. Nonhaematological toxicity was mild. The overall response rate in the assessable patients was 64%, with median progression-free survival of 38 weeks, and median survival of 70 weeks. The ETF regimen was found to be toxic, and it was not possible to escalate the dose of docetaxel above the first dose level. This regimen has therefore not been taken any further, but as a development of this a new study is ongoing, combining 3-weekly epirubicin, weekly docetaxel and capecitabine, days 1-14.     

Phase II trial of bevacizumab in combination with weekly docetaxel in metastatic breast cancer patients.

PURPOSE: To evaluate the safety and efficacy of bevacizumab and weekly docetaxel as first- or second-line therapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Twenty-seven MBC patients received i.v. bevacizumab at 10 mg/kg on days 1 and 15 in combination with i.v. docetaxel 35 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Primary end points were to assess toxicity, overall response rate, and progression-free survival. A secondary end point was to assess the relationship between plasma endothelial and cell adhesion markers and clinical outcomes. RESULTS: One-hundred fifty-eight treatment cycles were administered with a median of six cycles (range 1-15 cycles) per patient. The most common grade 4 toxicities per patient were as follows: 2 (7%)-pulmonary embolus, 1 (4%)-febrile neutropenia, and 1 (4%)-infection; grade 3 toxicities were 4 (15%)-neutropenia, 4 (15%)-fatigue, 2 (7%)-neuropathy, 2 (7%)-athralgias, 2 (7%)-stomatitis, 1 (7%)-pleural effusion, and 1 (4%)-hypertension. The overall response rate was 52% [95% confidence interval (95% CI), 32-71%], median response duration was 6.0 months (95% CI, 4.6-6.5 months), and the median progression-free survival was 7.5 months (95% CI, 6.2-8.3 months). In hypothesis-generating univariate and limited multivariate analyses, E-selectin was statistically significantly associated with response to the combination. CONCLUSION: Bevazicumab in combination with weekly docetaxel is active with acceptable toxicities in MBC. Additional studies evaluating E-selectin as a marker of response to bevacizumab-containing chemotherapy are warranted.     

Two weekly vinorelbine: administration in patients who have received at least two prior chemotherapy regimes for advanced breast cancer

This study examined the response to and toxicity of two weekly vinorelbine administration in patients with at least two prior chemotherapeutic treatments for advanced breast cancer. This single centre study enrolled 20 patients, 19 of whom had received prior taxane treatment for advanced breast cancer. Taxane treatment was in the form of docetaxel for all but 1 patient who had received paclitaxel. All patients had received two or more prior chemotherapeutic regimes for advanced breast carcinoma, including anthracyclines (epirubicin) in 19 patients. Vinorelbine 25 mg/m2 two weekly was given for 6 months, until disease progression or toxicity precluded further treatment. 5 earlier studied patients started vinorelbine at 25 mg/m2/week; all changed to the two weekly schedule, limiting the incidence and severity of neutropenia. 7 partial responses (PRs) out of 20 assessable patients (35% overall response rate, 95% confidence interval 15-59%) were noted, all PRs occurring in taxane pretreated patients. The median duration of response was 4 months whilst the median time to progression was 2.75 months. Overall, there were 7 neutropenic events (35%) of 2 week median duration, spanning common toxicity criteria (CTC) grades 1-3 in severity. 5 neutropenia cases (25%) occurred in patients whilst on two weekly vinorelbine. 2 cases (10%) required granulocyte colony stimulating factor support, 1 having had febrile neutropenia (52%). One case of thrombocytopenia, neurotoxicity and nausea (each CTC grade 1) were recorded. Although this study involves a small number of cases, these preliminary results suggest that two weekly vinorelbine is effective in heavily pretreated (including taxane pretreated) advanced breast carcinoma. Response is comparable with that of traditionally used weekly regimes, with markedly less toxicity.