Weekly epirubicin and paclitaxel with granulocyte colony-stimulating factor support in previously untreated metastatic breast cancer patients: a phase II study

We conducted a phase II study to determine the activity and tolerability of weekly epirubicin-paclitaxel and granulocyte colony-stimulating factor in breast cancer patients untreated for metastatic disease. The phase II study was designed following the Simon optimal-two stage method. Patients received epirubicin 25 mg/m and paclitaxel 80 mg/m every week, and granulocyte colony-stimulating factor on days 2 and 4 for 24 consecutive weeks in the absence of progression. From 1999 to 2004, 53 patients entered the study; 1093 weekly courses were delivered, with a median number of cycles of 22. Patients received a median relative dose intensity of 94%. No hematological grade 3-4 toxicities were observed. One patient had one episode of grade 3 mucositis and two patients (3.8%) suffered grade 2 asthenia. Eight patients (15.1%) experienced grade 2 neutropenia, grade 2 anemia was registered in seven patients (13.2%). No cardiotoxicity was observed. Ten out of 53 patients (18.9, 95% confidence interval 8.3, 29.4%) showed a complete response, whereas 28 (52.8, 95% confidence interval 39.4, 66.3%) had a partial response, with an overall response rate of 71.7% (95% confidence interval 59.6, 83.8%). In addition, 14 patients (26.4%) had stable disease. Median time to progression was 12 months (95% confidence interval 7, 17). Median response duration was 14 months (range 3-60). The 1-, 3- and 5-year survival rates were 90.1, 68.0 and 56.6%, respectively. In untreated metastatic breast cancer patients, the weekly administration of epirubicin and paclitaxel with granulocyte colony-stimulating factor support seems to be extremely tolerable and active, and deserves further investigation into a phase III trial.     

Monotherapy with docetaxel in second- or third-line treatment of anthracycline-resistant metastatic breast cancer

Nineteen breast cancer patients pretreated with one or two anthracycline-containing regimens for visceral metastases received i.v. docetaxel 100 mg/m2 on day 1, q 21d. Docetaxel was administered as second-line therapy in 11 patients, whereas eight patients received docetaxel in a third-line setting. In the second-line setting, complete response (CR) was achieved in two (18%), partial response (PR) in four (36%) and stable disease (SD) in three (27%) patients resulting in a response rate (RR) of 54%. In the third-line setting three (38%) patients experienced PR (RR 38%) and two (25%) SD. In the second-line setting, median time to progression was 6.5+/-3.9 months (range 2.1-15.8) versus 4.7+/-5.5 months (range 0.6-15.9) in the third-line setting. Median overall survival was 9.6+/-8.0 months (range 2.7-25.8) versus 11.2-6.1 months (range 4.8-18.7). Overall, no patient experienced treatment-limiting toxicities. We conclude that docetaxel induced responses in 48% of anthracycline-resistant patients enrolled into the present study. The safety profile of docetaxel was manageable and tolerable. Docetaxel represented efficacious treatment in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy.     

Weekly paclitaxel, 5-fluorouracil and folinic acid with granulocyte colony-stimulating factor support in metastatic breast cancer patients: a phase II study

We conducted a phase II study to determine the activity and tolerability of weekly paclitaxel, 5-fluorouracil (5-FU) and folinic acid plus granulocyte colony-stimulating factor (G-CSF) support in anthracycline-pre-treated or -resistant metastatic breast cancer patients. The phase II study was designed following the Simon optimal-two stage method. Patients received paclitaxel 80 mg/m, folinic acid 10 mg/m and bolus infusion of 5-FU 300 mg/m every week plus G-CSF on day 3 for 24 consecutive weeks in the absence of disease progression. From May 1998 to May 2000, 51 patients entered the study. Patients received a median relative dose intensity of 97.5% (range 81-100%). No severe toxicities were observed. Seven patients (14%) experienced neutropenia grade 2. Seven patients (14%) experienced grade 2 anemia. Two patients (4%) experienced severe asthenia. Three out of 50 evaluable patients [6%, 95% confidence interval (CI) 2-12.6%] showed a complete response, whereas 23 (46%, 95% CI 32.2-59.8%) had a partial response, with an overall response rate of 52% (95% CI 38.2-65.8%). In addition, eight patients (15.7%) had stable disease. In the 13 patients untreated for metastatic disease, the overall response rate was 92.3% (CI 77.8-100), with one complete response and 11 partial responses (84.6% CI 65-100%). In the whole group, the median time to progression and overall survival were 8 (range 1-18) and 14 months (95% CI 11-17), respectively. Thus, in metastatic breast cancer patients pre-treated with anthracyclines, the weekly administration of paclitaxel, 5-FU and folinic acid with G-CSF support seems to be extremely tolerable and active.     

吉西他滨联合多西他赛治疗蒽环类耐药性晚期乳腺癌的临床观察

目的 观察吉西他滨联合多西他赛治疗耐药性乳腺癌的近期疗效及不良反应.方法 2008年6月至 2012 年 3月对27例耐药性晚期乳腺癌采用吉西他滨1 000 mg/m2静脉滴注第1天、第8天;多西他赛75 mg/m2静脉滴注1 h,第1天;21 d为1个周期,连用2个周期后评价疗效和不良反应.结果 27例均完成2周期以上化疗,均可评价,其中5例完全缓解,13例部分缓解,6例稳定,3例进展,总有效率为66.7%.主要不良反应为胃肠道反应、骨髓抑制、皮疹,均可耐受.结论 吉西他滨联合多西他赛治疗蒽环类耐药性晚期乳腺癌的近期疗效较好,不良反应可以耐受,值得进一步临床研究.     

Biweekly administration of gemcitabine and cisplatin chemotherapy in patients with anthracycline and taxane-pretreated metastatic breast cancer

Gemcitabine and cisplatin are the active agents in metastatic breast cancer pretreated with anthracycline and/or taxane as a second line treatment. The present study was designed to assess the efficacy and safety of this regimen given biweekly schedule in these patients. Twenty-seven women, median age 57, with metastatic breast cancer previously treated with anthracycline and taxane were eligible for enrollment. Gemcitabine was administered intravenously on days 1 and 15 at a dose of 2,000 mg/m(2) and Cisplatin was given intravenously on day 1 and 15 at a dose of 50 mg/m(2). Treatment cycles were repeated on an outpatient basis every 28 days. Of all 27 evaluable patients, the overall response rate was 26% (7 of 27; 95% CI: 11-46%) with seven all partial responses. The stable diseases were found in 9 (33%) patients. At the time of last follow-up, 11 (41%) of the patients died of their disease progression. The median overall survival duration was 7.4 +/- 2.8 months. The 1-year overall survival rate was 46.9% +/- 12.3. Hematological toxicity was not found as the principal dose-limiting toxicity. Severe (grade III/IV) neutropenia was observed only one (4%) patients. No patient was complicated by febrile neutropenia and G-CSF usage was not performed. Grade III and IV anemia were seen in only 4 (15%) and thrombocytopenia was noted only one (4%) patients. Severe hepatic (n = 2) and renal toxicity (n = 1) were observed and these all recovered completely without complication. Several other severe non-hematological side effects were managed easily. Permanent dose reductions were necessary in 9 (33%) patients and chemotherapy administration was also delayed in 7 (26%) patients because of delayed both hematological and non-hematological toxicity recovery. Treatment was discontinued in one (4%) patient due to severe fatigue and deteriorating performance status. In conclusion, gemcitabine and cisplatin combination therapy with this biweekly schedule and dosage is moderately active and extremely safe in patients with metastatic breast cancer previously treated with anthracycline and taxanes.     

长春瑞滨联合吉西他滨治疗晚期乳腺癌50例临床分析

目的 观察长春瑞滨（NVB）联合吉西他滨（GEM）治疗蒽环类和紫杉类药物耐药的晚期乳腺癌患者（ATRMBC）的临床效果. 方法 采用NVB联合GEM方案（GN方案）治疗50例蒽环类和紫杉类药物耐药的晚期乳腺癌患者,NVB 25 mg/m2静脉滴注,第1、8天;GEM 1 000 mg/m2静脉滴注,第1、8天;21 d为1个周期,最多接受6个周期的化疗. 结果 50例患者完全缓解2例（4%）,部分缓解19例（38%）,稳定22例（44%）,进展7例（14%）;有效率42%;平均随访17.2个月,中位生存期16.8个月.主要不良反应为恶心、呕吐及骨髓抑制. 结论 NVB联合GEM是治疗蒽环类和紫杉类药物耐药的晚期乳腺癌患者的有效方案,患者对不良反应能够耐受.     

Paclitaxel-ifosfamide for anthracycline-resistant advanced breast cancer

Thirty-one patients with advanced breast cancer either resistant to anthracycline-based regimens or relapsing after anthracycline-based adjuvant chemotherapy received a combination of a 3-h infusion of paclitaxel 135 mg/m2 on day 1 and a 4-h infusion of ifosfamide 1.7 g/m2 on days 2 to 4 of a 22-day cycle. For inclusion in the study, patients had to have measurable or evaluable progressive metastasis or local disease, and to have received only one prior regimen for metastatic disease; 31 patients with a median age of 49 years (range: 30-69) entered the study. Nine patients (29%) had lung metastasis, while 17 (55%) had liver metastasis, and 19 (61%) had bone metastasis. Only seven patients (23%) had lymph node metastasis and four (13%) had skin metastasis. A median of seven cycles of treatment was delivered. Responses were evaluated according to World Health Organization (WHO) guidelines and side effects according to National Cancer Institute (NCI) criteria. A panel of oncologists and one radiologist reviewed all responses. At baseline, only three patients (10%) were free from the adverse effects of the prior therapy; severe nonhematological toxicity occurred in less than 8% of patients. However neutropenia grade 3-4 occurred in 88%, while only 3% had severe infections. Severe thrombocytopenia and anemia were rare (4% and 8%, respectively). The overall response rate was 42% (13% complete response). Median survival and progression-free survival rates after initiation of treatment were 19.3 months and 6.1 months, respectively. With an objective response rate of 42% and median survival of 19 months, the combination of paclitaxel and ifosfamide seems to offer a promising regimen with acceptable side effects in advanced breast cancer patients relapsing after anthracycline-based adjuvant treatment or resistant to anthracycline treatment.     

Phase II study of docetaxel and epirubicin in Chinese patients with metastatic breast cancer

The efficacy and safety of docetaxel-epirubicin chemotherapy in the treatment of metastatic breast cancer was investigated in Chinese women. Three-weekly cycles comprised epirubicin 75 mg/m2 i.v. followed 1 h later by docetaxel 75 mg/m2 i.v. After 3 cycles, responding patients received a further 3 cycles, followed by 3 cycles of docetaxel alone. Forty-six patients entered the study, of whom 37% had received prior adjuvant chemotherapy. Three patients withdrew due to toxicity and were not evaluable for response. There were five complete responses and 31 partial responses, giving an overall response rate of 83.7% (95% CI 72.7-94.8%). The median time to progression was 10.96 months (95% CI 7.76-12.86) and median survival was 24.2 months (95% CI 16.6-). The most common grade 3/4 adverse events were neutropenia (96% of patients) and neutropenia with fever (39%). Hepatotoxicity occurred in six patients, two being attributable to hepatitis B virus reactivation. No patients suffered grade 3/4 cardiac toxicity and there were no treatment-related mortalities. Quality of life aspects deteriorated after 3 cycles, but there was a trend towards improved emotional aspects after 9 cycles. We conclude that docetaxel-epirubicin chemotherapy is highly effective for recurrent metastatic/locoregional breast cancer, with myelosuppression being the main toxicity.     

Single-agent docetaxel in metastatic breast cancer patients pre-treated with anthracyclines and paclitaxel: partial cross-resistance between paclitaxel and docetaxel

The purpose of this study was a retrospective analysis of docetaxel in a cohort of anthracyclines and paclitaxel pretreated patients with metastatic breast cancer. From July 1998 to June 1999, 24 consecutive patients were included for this study. The regimen consisted of docetaxel 75 mg/m2 in combination with a 3-day schedule of dexamethasone every 3 weeks until disease progression or unacceptable toxicity. The median age of patients was 53 (ranged 32-67) years with a median performance status of 2. Twenty of the 24 patients (84%) had measurable disease. The median number of organs involved was 2 (range 1-4). A total of 146 cycles chemotherapy were given with a mean of 6. There was a 25% (six of 24) overall response rate including one complete response, 37.5% stable disease and 37.5% progressive disease. The major toxicity included grade 3-4 leukopenia (41.7%) and eight episodes of infection. No treatment-related death was observed. The responders included patients refractory to or resistant to prior paclitaxel treatment. The median survival and median time to disease progression was 12 and 9 months, respectively. We conclude that docetaxel has a modest activity in breast cancer patients pre-treated with anthracyclines and paclitaxel, indicating a partial cross-resistance between paclitaxel and docetaxel.     

Phase II study of gemcitabine in combination with vinorelbine versus gemcitabine followed by vinorelbine for metastatic breast cancer

Background No clear data are available concerning the superiority of combination chemotherapy to sequential therapy using agents beyond 1st or 2nd line chemotherapy for treating patients with metastatic breast cancer. Methods Patients were randomized to receive a combination of gemcitabine and vinorelbine or gemcitabine until disease progression followed by vinorelbine monotherapy. Quality of life was assessed using EORTC QLQ-C30 questionnaires. Results Forty-two patients were randomized to the combination arm and 40 were randomized to the sequential arm. Baseline characteristics were well balanced between the arms. The median number of chemotherapy cycles was 4 (range, 1–23) for the combination arm and 6 (range, 1–25) for the sequential arm. Patients receiving combination therapy had a higher composite response rate (26.8% vs. 12.5%; P = 0.106) but a shorter median time to treatment failure (3.6 vs. 4.4 months, P = 0.252) as compared to patients receiving sequential monotherapy. Median overall survival for the combination and sequential arms was 10.6 months and 8.9 months, respectively (P = 0.436). Toxicities were manageable and similar in both arms. Quality of life measurements in global health, role, and social function were superior in the combination arm (P < 0.05). Conclusions Combined gemcitabine and vinorelbine therapy appears comparable to sequential monotherapy for heavily pretreated patients with metastatic breast cancer as demonstrated by improved quality of life outcomes with similar therapeutic efficacies and incidences of adverse events.     

Weekly docetaxel in patients with pretreated metastatic breast cancer: a phase II trial

Docetaxel has consistently demonstrated its high activity as an antineoplastic agent in the treatment of metastatic breast cancer. However, 90% of patients receiving the recommended dose of 100 mg/m2 every 3 weeks will develop grade 3 or 4 neutropenia. Recent data suggest that the safety profile of a weekly docetaxel regimen compared favorably with the standard 3-week schedule. Thus, we initiated a phase II study to assess the efficacy and toxicity of weekly docetaxel in pretreated patients with metastatic breast cancer. Twenty patients with advanced, anthra-cycline-refractory breast cancer were included in this phase II trial. Docetaxel was administered at a starting dose of 40 mg/m2, repeated once a week for 3 consecutive weeks followed by a 1-week rest period (1 cycle). Patients were evaluated for tumor response every 8 weeks (after every other cycle). Therapy was continued for a maximum of six courses in patients showing tumor response or stable disease. Twenty patients received a total of 204 weekly infusions of docetaxel. The mean number of treatments was 10.2 (range 1-18). Eighteen patients were assessable for response. Five patients achieved a partial response and six patients showed either stable disease or a minor response. Seven patients had disease progression. The median survival was 7.8 months. Grade 3/4 leukopenia occurred in two patients. No other grade 3 or 4 hematologic toxicities were observed. The following grade 3/4 non-hematologic toxicities were seen: nausea/vomiting (one patient), infection (one patient), mucositis (two patients) and diarrhea (one patient). Three patients withdrew from the study due to dose-limiting toxicities (one due to severe neutropenia and two due to mucositis). We conclude that administration of docetaxel at a dose of 40 mg/m2 was effective and well tolerated even in heavily pretreated patients with metastatic breast cancer. This regimen is associated with only mild myelosuppression.     

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

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

Phase I study of carboplatin, docetaxel and irinotecan with recombinant human granulocyte colony stimulating factor support in patients with advanced non-small cell lung cancer

A phase I study was conducted in patients with stage IIIB or IV non-small cell lung cancer to determine the maximum tolerated dose (MTD) of irinotecan combined with a fixed schedule of docetaxel and carboplatin with recombinant human granulocyte colony stimulating factor (rhG-CSF) (nartograstim) support. Docetaxel was given at 60 mg/m2 on day 1 with carboplatin. The dose of carboplatin was calculated using the Calvert formula to achieve an estimated AUC of 5.0 mg/ml x min. Irinotecan was administered at a starting dose of 40 mg/m2 on day 1 and increased in increments of 10 mg/m2. rhG-CSF was given at 1 microg/kg on days 5-15. Cycles were repeated every 3 weeks. Between February 1998 and March 1999, 22 patients were enrolled in this phase I study. Five patients were chemotherapy naive. The MTD of irinotecan was 60 mg/m2. Diarrhea was considered to be the dose-limiting toxicity. The irinotecan dose intensity of 16.7 mg/m2/week was low compared with other irinotecan-containing regimens. The overall response rate was 38.1% and median survival was 278 days. Irinotecan 50 mg/m2 in combination with 60 mg/m2 docetaxel and carboplatin on day 1 with rhG-CSF support is recommended for phase II study. The response rate and survival data in this phase I study are encouraging.     

Predictors of response of patients with solid tumors to granulocyte colony-stimulating factor

Background Granulocyte colony-stimulating factor administration is an important component of supportive therapy in chemotherapy-induced leukopenia. Although patient response to granulocyte colony-stimulating factor administration is known to vary, the factors responsible for poor response have not been identified. Objective To identify the predictors of the responses of patients with solid tumors to granulocyte colony-stimulating factor. Setting A 600-bed university hospital offering secondary and tertiary care in Japan. Methods This retrospective cohort study examined the response of 181 patients with solid tumors who were administered prophylactic granulocyte colony-stimulating factor for the first time after they developed severe grade 3/4 leukopenia (white blood cell count <2,000 × 10^?9/L) because of adjuvant or neoadjuvant chemotherapy. The granulocyte colony-stimulating factor response was defined as the length of the leukocyte recovery period, which was assessed as the period within which the normal white blood cell count (white blood cell count >3,000 × 10^?9/L) is reached after the first dosage of granulocyte colony-stimulating factor. After classification of the patients as either poor or normal granulocyte colony-stimulating factor responders according to the confidence interval of the recovery period, their characteristics were compared. Main outcome measure The time for recovery to normal white blood cell count was 2–7 days (90 % confidence interval), and the cutoff value for differentiating poor responders (n = 14) from normal responders (n = 167) was 8 days. Univariate analysis identified previous radiotherapy, number of chemotherapy courses, high granulocyte colony-stimulating factor dosage, and hypoalbuminemia to be significantly associated with granulocyte colony-stimulating factor response. Multivariate analysis identified undergoing four or more chemotherapy courses (odds ratio = 5.09; 95 % confidence interval, 1.14–22.71) and heart failure (odds ratio = 5.96; 95 % confidence interval, 1.09–32.57) to be significantly associated with poor granulocyte colony-stimulating factor response. Conclusions Undergoing four or more chemotherapy courses and heart failure are independent risk factors for poor response to granulocyte colony-stimulating factor. These findings may help prevent the complications of leukopenia during chemotherapy and highlight the need to develop better strategies for preventing and treating infectious disease in patients undergoing granulocyte colony-stimulating factor administration.     

Phase II study of an oxaliplatin/vinorelbine combination in patients with anthracycline- and taxane-pre-treated metastatic breast cancer

A phase II study was conducted to evaluate the safety and efficacy of an oxaliplatin (OXA)/vinorelbine (VNB) combination in metastatic breast cancer (MBC) patients pre-treated with anthracyclines and taxanes. Patients received OXA at 130 mg/m (2-h i.v.), day 1, and VNB days 1 and 8 at 24-26 mg/m repeated every 3 weeks. Forty-two patients (median age 54; 64% with liver metastasis, 67% taxane resistant/refractory and 38% anthracycline resistant/refractory) were treated. A median of 4 cycles of treatment was given per patient, with 31% receiving 6 or more. Eleven partial responses and 16 patients with stable disease (five lasting more than 4 months) in 41 eligible patients were seen, for an overall response rate of 26.8% (95% confidence interval 14.2-42.9). Median follow-up was 15.9 months (7.2-30.6), median time to progression was 3.4 months and estimated overall survival was 12.7 months (20 events). Thirty-three patients experienced (National Cancer Institute Common Toxicity Criteria version 2) grade 3-4 neutropenia (one case of febrile neutropenia) and three patients had severe constipation requiring hospitalization. Nine patients developed grade 3 OXA-specific neurotoxicity. There were no treatment-related deaths. We conclude that OXA 130 mg/m (day 1) and VNB 24 mg/m (day 1 and 8) combination given every 3 weeks is effective with a good safety profile in MBC patients previously treated with anthracyclines and taxanes.     

Oral vinorelbine: role in the management of metastatic breast cancer

The treatment of advanced breast cancer is continually evolving, with the aim of improving the quality and duration of remission and, in some instances, survival. In this setting, the importance of quality of life cannot be underestimated, and growing attention is being paid to treatment convenience and compliance. New anticancer agents have improved efficacy, but for many of them, toxicity often remains a problem. Vinorelbine seems to represent both an active and a well tolerated treatment for metastatic breast cancer. In particular, the oral formulation has similar efficacy to that of the injectable formulation and has demonstrated generally favourable tolerability, with a high degree of acceptance by both patients and physicians. The availability of this and other novel, well tolerated and effective treatments provides greater potential to tailor treatment to meet individual patient needs and, therefore, also provide the potential to improve patient outcomes. Preliminary data suggest that oral vinorelbine may permit continued, effective chemotherapy when further parenteral therapy with more intensive and more toxic agents is considered inappropriate. Early findings also suggest that oral vinorelbine, when administered together with another new oral agent, capecitabine, may be a valid choice in metastatic breast cancer treatment. Furthermore, vinorelbine plus the monoclonal antibody trastuzumab, with or without oral capecitabine, appears to be another regimen that may be worthy of additional study in patients with human epidermal growth factor-2 positive advanced breast cancer.     

Phase I/II study of biweekly vinorelbine and oxaliplatin as first-line treatment in patients with metastatic breast cancer

The objective of this phase I/II study was to establish the recommended dose of biweekly vinorelbine and oxaliplatin in patients with metastatic breast cancer and to evaluate the efficacy and safety profile of this schedule as first-line treatment. Four different dose levels of vinorelbine and oxaliplatin were selected for the phase I study: (i) 25 and 80 mg/m2; (ii) 25 and 90 mg/m2; (iii) 25 and 100 mg/m2; and (iv) 30 and 90 mg/m2; respectively. At least three patients were treated at each dose level. Overall, 12 patients were included in the phase I trial. No dose-limiting toxicities occurred at any dose level. Therefore, the fourth dose level (30 mg/m2 of vinorelbine and 90 mg/m2 of oxaliplatin) every 2 weeks was selected for the phase II trial. In this part, 44 patients were included and 61% completed the eight 2-week cycles of study treatment. On an intention-to-treat basis, overall response rate was 59%, and median progression-free survival and overall survival were 9.2 months (95% confidence interval: 7.6-10.9) and 18.6 months (95% confidence interval: 14.4-22.9), respectively. The main severe toxicities were neutropenia (46%) and fatigue (14%). We conclude that the biweekly combination of vinorelbine and oxaliplatin at doses of 30 mg/m2 and 90 mg/m2, respectively, is highly active and well tolerated as first-line treatment for patients with metastatic breast cancer.