Adherence with oral chemotherapy: results from a qualitative study of the behaviour and representations of patients and oncologists.

Oral chemotherapy is increasingly used in oncology. Poor adherence, that is, non-respect of medical advice about taking the therapy and surveillance of adverse effects, is the main risk associated with this administration route. Poor adherence may be explained by non-adherence by the patient to the treatment, misunderstanding the advice or it could also reflect the poor adaptation of the healthcare team to a new administration route. Here we report the results from a qualitative study that aimed to describe and understand existing practice for capecitabine, an oral chemotherapy, which is used for the treatment of metastatic breast and colon cancer. We interviewed 42 patients who were receiving oral capecitabine in groups and individually as well as 10 prescribers. This study was carried out in two specialist cancer centres. The results showed a wide diversity in the prescribers' practices, who make decisions based on their experience of practice guidelines for intravenous chemotherapies. Although the results for the patients do not suggest deliberate non-adherence, they show poor observance of the dose schedule. The most important result of this study is the patient's inability to identify and to report important signs of harmful toxicity.

Phase II of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer, previously treated with platinum and taxanes.

BACKGROUND: A prospective phase II study was conducted to evaluate the efficacy and toxicity of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer. PATIENTS AND METHODS: Patients had a maximum of three prior chemotherapy lines with no more than two prior platinum-containing regimens and a progression-free interval after the last dose of platinum <12 months. A total dose of 4 mg/m(2)/cycle (0.8 mg/m(2)/day from day 1 to day 5) was administered, repeated every 28 days. RESULTS: From June 2005 to December 2005, 69 assessable patients were enrolled. The best overall response to study treatment by combined CA-125 and RECIST criteria was partial response in 17 patients (24.6%) and disease stabilization in 22 patients (31.9%). The median time to progression and overall survival were 3.8 and 16.2 months, respectively. A total of 312 cycles were administered. Neutropenia grade 4 and thrombocytopenia grade 4 occurred in 17.4% and 7.2% of patients, respectively. Diarrhea grade 4 was never observed. Asthenia and fatigue were reported by 36.2% and 18.8% of patients, but were all grade 2 or less. CONCLUSION: Gimatecan is a new active agent in previously treated ovarian cancer with myelosuppression as main toxicity.

A risk model for severe anemia to select cancer patients for primary prophylaxis with epoetin alpha: a prospective randomized controlled trial of the ELYPSE study group.

BACKGROUND: Epoetin (EPO) administration reduces the need for transfusion. Identifying patients at high risk of anemia requiring red blood cell (RBC) transfusion is needed. This multicentric phase III trial tested epoetin alpha (EPOalpha) administration according to our risk model on the basis of three clinical parameters: hemoglobin (Hb) <12 g/dl, lymphocytes 1. PATIENTS AND METHODS: Patients >or=18 years with chemotherapy-treated solid or hematologic tumors were randomized to 150 UI/kg/TIW s.c. EPOalpha (arm 1) or no EPOalpha (arm 2) and stratified on Hb level at day 0, lymphocyte count, and PS. The primary end point was transfusion rate; secondary end points included overall survival (OS), safety, and quality of life. RESULTS: From September 2000 to January 2005, 218 patients (median age 64 years, 42.7% males) with principally breast cancer, sarcoma, or lung carcinoma were included. In total, 93% patients had PS >1 and 35% had

A phase Ib trial of docetaxel, carboplatin and erlotinib in ovarian, fallopian tube and primary peritoneal cancers.

The safety and maximum tolerated dose (MTD) of erlotinib with docetaxel/carboplatin were assessed in patients with ovarian cancer. Chemonaive patients received intravenous docetaxel (75 mg m(-2)) and carboplatin (area under the curve 5) on day 1 of a 3-week cycle, and oral erlotinib at 50 (cohort 1), 100 (cohort 2a) or 75 mg day(-1) (cohort 2b) for up to six cycles. Dose-limiting toxicities were determined in cycle 1. Forty-five patients (median age 59 years) received treatment. Dose-limiting toxicities occurred in 1/5/5 patients (cohorts 1/2a/2b). The MTD of erlotinib in this regimen was determined to be 75 mg day(-1) (cohort 2b; the erlotinib dose was escalated to 100 mg day(-1) in 11 out of 19 patients from cycle 2 onwards). Neutropaenia was the predominant grade 3/4 haematological toxicity (85/100/95% respectively). Common non-haematological toxicities were diarrhoea, fatigue, nausea and rash. There were five complete and seven partial responses in 23 evaluable patients (52% response rate). Docetaxel/carboplatin had no measurable effect on erlotinib pharmacokinetics. In subsequent single-agent maintenance, erlotinib was given at 100-150 mg day(-1), with manageable toxicity, until tumour progression. Further investigation of erlotinib in epithelial ovarian carcinoma may be warranted, particularly as maintenance therapy.

Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole. Prevention with bisphosphonates.

Aromatase inhibitors have demonstrated their superiority to tamoxifen as adjuvant therapy for early breast cancer in postmenopausal women, but are associated with an increased risk of fractures. The aim of our study was to analyze bone loss, bone turnover and their determinants in postmenopausal women treated with anastrozole. We investigated bone loss and bone turnover markers (BTM) in a prospective open cohort study of 118 postmenopausal women treated with anastrozole for an early hormone-dependent breast cancer. Women without osteoporosis were not treated and compared with an age-matched control group of 114 healthy women. Osteoporotic patients (T-scoreor=6 courses) and a marked antiestrogenic response--defined by a level of 17beta-estradiol50% between baseline and 1 year--were associated with greater bone loss. In multivariate model, women in the highest quartile of bone loss at the spine (>5.6% at 1 year) and hip (>4.9%) had a marked antiestrogenic response with OR of 10.4 [95% C.I. 1.9-57.2] (p=0.007) and 5.7 [1.3-25] (p=0.024) respectively. Among patients in the surveillance group, those with a normal T-score at both sites (n=46) had also a significant bone loss at spine -3.3+/-0.5% [-4.3 to -2.3], p<0.0001 and at the hip -2.9+/-0.6% [-4.1 to -1.7] p<0.0001. In osteoporotic women treated simultaneously with anastrozole and risedronate, bone loss was prevented at hip, and increased at the spine (+4.1+/-0.9% [2.3 to 5.9], p=0.008), and BTM decreased (-24%, -39% for CTX, p=0.003 and 0.001 vs. changes in the untreated group). Anastrozole increases bone turnover and induces an accelerated bone loss that is significantly related to the suppression of 17beta-estradiol production induced by aromatase inhibitor. The bisphosphonate risedronate prevents anastrozole induced bone loss.

[Evaluation of treatment relating to gestational trophoblastic tumor registered to the French Trophoblastic Disease Reference Center (TDRC) in Lyon from 1999 to 2005]. / Evaluation de la prise en charge des tumeurs trophoblastiques gestationnelles enregistrées au Centre de référence des maladies trophoblastiques de Lyon de 1999 à 2005.

OBJECTIVES: The aim of this study was both to analyse if gestational trophoblastic neoplasia (GTN) registered to the French Trophoblastic Disease Reference Center (TDRC) in Lyon (France) were managed according to the FIGO criteria for diagnosis of GTN and if chemotherapy was adapted to the 2000 FIGO prognostic scoring system. PATIENTS AND METHODS: Retrospective, descriptive analysis of 167 GTN registered to GTC of Lyon between 1999 and 2005. RESULTS: On the one hand, 66% of women (104/158) had a diagnosis of GTN according to FIGO criteria. One third (n=54) of the patients therefore had a premature or erroneous diagnosis of a tumor, when the treatment started. No supporting element of this premature diagnosis has been found out for 26 patients. The identification of lung and vaginal metastasis and histological diagnosis of invasive mole appeared as the most mentioned inappropriate criteria for diagnosis. On the other hand, chemotherapy was adapted to 2000 FIGO scoring in 91, 5% of cases. Twelve low risk GTN were treated with polychemotherapy and two high risk GTN were treated with monochemotherapy. Moreover 29% of the patients received a non adequate treatment due to deviations from the recommended protocol. DISCUSSION AND CONCLUSION: Non respect of FIGO criteria for the diagnosis of GTN can lead to erroneous diagnosis of tumors. Identification of lung or vaginal metastasis or diagnosis of invasive mole should not automatically justify the diagnosis of gestational trophoblastic neoplasia if the decrease in HCG occurs properly. Respect of FIGO criteria for the diagnosis of GTN and adaptation of chemotherapy to 2000 FIGO scoring are necessary to avoid inadequate treatment of gestational trophoblastic neoplasia.

Intensification of adjuvant chemotherapy: 5-year results of a randomized trial comparing conventional doxorubicin and cyclophosphamide with high-dose mitoxantrone and cyclophosphamide with filgrastim in operable breast cancer with 10 or more involved axillary nodes.

PURPOSE: To determine whether intensifying the dose of adjuvant chemotherapy improves the outcome of women with primary breast cancer and 10 or more involved axillary nodes. PATIENTS AND METHODS: Patients (n = 150) were randomized to receive either four cycles of standard doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 3 weeks (arm A) or four courses of intensified mitoxantrone 23 mg/m(2) plus cyclophosphamide 600 mg/m(2), with filgrastim 5 g/kg/d from days 2 to 15, every 3 weeks (arm B). Disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) were determined using life-table estimates. RESULTS: There were no significant differences in DFS (P =.44), DDFS (P =.67), or OS (P =.99) between the two groups at 5 years; DDFS was 45% (arm A) versus 50% (arm B), and DFS was 41% versus 49%, respectively. Five-year survival was similar in both arms (61% v 60%, respectively). Failure to note an intergroup difference in outcome was unrelated to relative dose-intensity. Analysis of patients with 15 or more positive nodes revealed a significant difference in 5-year DDFS (19% v 49% in arm B; P =.01). Toxicity was generally mild in both groups, with no toxic death. The incidence of febrile neutropenia was low (0.3% v 3%). Alopecia was less frequent in arm B (P <.001). CONCLUSION: This randomized trial confirms the feasibility of administering mitoxantrone 23 mg/m(2) with cyclophosphamide and filgrastim. Although there was no significant difference between conventional and intensified arms at 5 years, according to subgroup analysis, intensified treatment may decrease the risk of relapse in patients with 15 or more positive nodes compared with doxorubicin an cyclophosphamide.

Topotecan, an active drug in the second-line treatment of epithelial ovarian cancer: results of a large European phase II study.

PURPOSE: Topotecan is a topoisomerase I inhibitor with preclinical activity against various tumor types. We conducted a large multicenter phase II study with topotecan in ovarian cancer in patients who had failed to respond to one prior cisplatin-based chemotherapeutic regimen. PATIENTS AND METHODS: Topotecan 1.5 mg/m2/d was administered intravenously by 30-minute infusion for 5 days repeated every 3 weeks. As the cisplatin-free interval relates to response in subsequent treatment, patients were stratified in subgroups, ie, cisplatin-refractory, cisplatin-resistant, and cisplatin-sensitive. RESULTS: One-hundred eleven patients entered the study. Nineteen patients were considered to be ineligible; 92 patients were assessable for response. A total of 552 courses were given (median, four per patient; range, one to 17). The major toxicities were leukocytopenia and neutropenia, which were grade 3 to 4 in 54.2% and 69.1% of courses, respectively, but with only 4.3% of these being grade 4 neutropenia plus fever or infectious complications. Prophylactic granulocyte colony-stimulating factor (G-CSF) was given in 20.5% of courses to maintain dose-intensity. Other relatively frequent side effects were alopecia (82%), nausea (36.4%), and vomiting (17.5%). The overall response rate was 16.3%, with one complete response (CR) and 14 partial responses (PRs). In the cisplatin-refractory, cisplatin-resistant, and cisplatin-sensitive strata, the response rates were 5.9%, 17.8%, and 26.7%, respectively. The median duration of time of documented response was 21.7 weeks (range, 4.6 to 41.9). CONCLUSION: Topotecan in a daily-times-five schedule is an effective regimen as second-line treatment in ovarian cancer. Further investigations of topotecan in ovarian cancer, including first-line use and combination with other active agents, are indicated.

Intraperitoneal recombinant interferon gamma in ovarian cancer patients with residual disease at second-look laparotomy.

PURPOSE: The purpose of this study was to evaluate the efficacy and tolerance of recombinant human interferon gamma (rIFN-gamma) as second-line treatment in patients with persistent disease at second-look laparotomy. PATIENTS AND METHODS: One hundred eight patients with residual disease at second-look laparotomy were treated with rIFN-gamma (20 x 10(6) IU/m2) administered intraperitoneally (IP) twice a week for 3 to 4 months. In the absence of clinically assessable disease, response to rIFN-gamma was assessed with a third-look laparotomy. RESULTS: Of 98 assessable patients, 31 (32%) achieved a surgically documented response, including 23 patients (23%) with a complete response (CR). The age and size of residual tumor were significant prognostic factors for the response to rIFN-gamma. A 41% CR rate was observed in 41 patients younger than 60 years and with residual tumor less than 2 cm. The probability of response was independent of previous response to first-line chemotherapy. The median duration of response was 20 months and the 3-year survival rate in responders was 62%. Response to rIFN-gamma was the most significant prognostic factor for survival of patients with residual disease. Adverse events included fever, flu-like syndrome, neutropenia, and liver enzyme disturbances. No significant peritoneal fibrosis was noted. CONCLUSION: These results support the potential interest of IP rIFN-gamma as adjuvant treatment in ovarian cancer. Controlled prospective trials are required to determine its place in the therapeutic strategy of this malignancy.

Effects of tamoxifen and octreotide LAR on the IGF-system compared with tamoxifen monotherapy.

The insulin-like growth factor (IGF)-system was evaluated in 150 breast cancer patients participating in a randomised phase III trial comparing octreotide pamoate and tamoxifen with tamoxifen+placebo. Alterations in the IGF-system in the two treatment arms and individual changes with respect to outcome were compared. Serum IGF-I and -II, free IGF-I, and insulin-like growth factor binding protein 1-3 (IGFBP1-3) were measured by radioimmmunoassay (RIA)/immunoradiometric assay (IRMA) and IGFBPs by Western ligand blots (WLB) before and during treatment. Combined treatment caused a higher increase in IGFBP-1 and larger suppression of total and free IGF-I, IGF-II, and IGFBP-3 (P<0.01 for all), but less suppression of IGFBP-2 (P<0.05) compared with tamoxifen monotherapy. An increase in IGFBP-2 25% was associated with decreased progression-free survival (PFS) in the total patient population and combined treatment group. Similar response rates and time to progression in the treatment arms suggests moderate suppression of circulating IGF-I has no influence on clinical outcome.

A phase II study of intraperitoneal radioimmunotherapy with iodine-131-labeled monoclonal antibody OC-125 in patients with residual ovarian carcinoma.

Standard treatment of advanced ovarian cancer is a combination of surgery and chemotherapy. Additional therapies using the i.p. route are considered as a potential means of improving the locoregional control rate. This Phase II study evaluated the efficacy of i.p. radioimmunotherapy (RIT) in patients with minimal residual ovarian adenocarcinoma after primary treatment with surgery and chemotherapy. Between February 1995 and March 1996, six patients with residual macroscopic (<5 mm) or microscopic disease as demonstrated by laparotomy and multiple biopsies received i.p. RIT. All had initial stage III epithelial carcinoma and were treated with debulking surgery and one line (four patients) or two lines (two patients) of chemotherapy. RIT was performed with 60 mg of OC 125 F(ab')2 monoclonal antibody labeled with 4.44 GBq (120 mCi) of 131I injected 5-10 days after the surgical procedure. Systematic laparoscopy or laparotomy with multiple biopsies performed 3 months after RIT in five patients (clinical progression was seen in one patient) showed no change in three patients and progression in two patients. Toxicity was mainly hematological, with grade III neutropenia and thrombocytopenia in two patients. Human antimouse antibody production was demonstrated in all six patients. This study showed little therapeutic benefit from i.p. RIT in patients with residual ovarian carcinoma.

Impact of screening on clinicopathological features and treatment for invasive breast cancer: results of two national surveys.

PURPOSE: Several studies showed a breast cancer downstaging due to screening. A first national survey was conducted in France in 2001-2002 to evaluate in the current clinical practice the clinicopathological features and treatments of 1049 firstly operated breast cancers. In order to assess the impact of the national screening program implemented in all regions in France in 2004, a new survey was performed in 2007-2008. MATERIAL: The new survey included 1433 firstly operated breast cancers prospectively collected. These new data were compared to the results of the first national survey. RESULTS: According to TN classification, we found in the second survey T0: 27.6%, T1: 48.6%, T2: 21.3%, T3T4: 3.8% and Tx: 0.7%. Infiltrating ductal and lobular carcinomas represented 80% and 13% of tumours. Hormone receptors were positive in 85.3% and Her-2 overexpressed in 12.4% of tumours (83.9% and 20.6% in the first survey); 68.2% and 32% were pN0 and pN1-3. Lumpectomy and mastectomy were performed in 77% and 23% of the cases. Axillary dissection, sentinel node biopsy or both were performed in 42.6%, 41% and 16.4% of the cases, respectively. Radiotherapy, chemotherapy, hormonotherapy and trastuzumab were given to 93%, 51%, 83% and 9.3% of the patients. Compared with the results from the first survey, we found an increase of infraclinical lesions (T0 from 8.4 to 27.6%) and a wide decrease of pN+ rate (from 44% to 32%). The mastectomy rate was constant (23%), as well as radiotherapy use, whereas chemotherapy use decreased from 62.8 to 55.6%. CONCLUSION: A complete national screening coverage clearly provides a favourable modification of breast cancer clinicopathological features. Both locoregional and adjuvant treatments were greatly downscaled.

Carboplatin in combination therapy for ovarian cancer.

Cisplatin today is a cornerstone of combination chemotherapy for ovarian cancer. Carboplatin seems equal to cisplatin in antitumour activity, but has a different toxicity profile. After a feasibility study, a randomized phase III study in ovarian cancer stage II, III, and IV was undertaken, comparing carboplatin with cisplatin in combination with cyclophosphamide, doxorubicin and hexamethylmelamine. Preliminary analysis of this study reveals no statistically significant difference in response rate. Notwithstanding equal haematological toxicity, the other side effects evoked by carboplatin in combination treatment are much milder than those evoked by cisplatin. Further analysis will be necessary to draw definite conclusions about the results obtained.

Predicting cancer-associated anaemia in patients receiving non-platinum chemotherapy: results of a retrospective survey.

A 2-year retrospective chart survey of 1064 patients with colorectal, breast, lung or ovarian cancer, Hodgkin's disease, or non-Hodgkin's lymphoma was conducted at 24 centres in France to determine the prevalence of anaemia (haemoglobin (Hb) levels < or = 120 g/l) and need for transfusion in patients who received non-platinum-based chemotherapy for more than three cycles or 3 months. Baseline Hb levels documented anaemia in 37.1% of patients (all tumour types). By cycle 3, the prevalence of anemia increased to 54.1% of patients and remained over 50% at cycle 4. At some time during chemotherapy 14.5% of patients were transfused. Predictive risk factors for anaemia requiring transfusion included low baseline Hb, decrease in Hb during the first month of chemotherapy, primary tumour site, prior blood transfusions and duration of chemotherapy. By early identification of patients at the highest risk of developing anaemia, interventions such as epoetin alfa can be employed to reduce or eliminate the need for transfusions.

Pharmacokinetically guided dosing for intravenous melphalan: a pilot study in patients with advanced ovarian adenocarcinoma.

Pharmacokinetically guided administration of melphalan was investigated during a pilot study in patients with advanced ovarian adenocarcinoma. The schedule involved a fixed dose on day 1 (7.9 mg) followed by a second dose on day 2, calculated on the basis of pharmacokinetic data to achieve a target area under the concentration-time curve (AUC). 20 courses of intravenous melphalan were administered to 7 patients. AUC, standardised to 1 mg/m2, ranged between 4.3 and 8.9 (mg/l) min. In 12 fully evaluable courses, less than 15% deviation from the target AUC was found, showing that AUC monitoring was possible by means of the test dose. Pharmacodynamic effects showed a positive correlation with melphalan AUC. Myelosuppression appeared at 47 (mg/l) min and grade 3 or 4 haematological toxicities were observed in 4 cycles, associated with AUC values ranging between 86 and 112 (mg/l) min. Relative leucocyte decreases were well correlated with AUC values.

Phase II study of weekly 4'-epidoxorubicin in patients with metastatic squamous cell cancer of the cervix: an EORTC Gynaecological Cancer Cooperative Group Study.

In this study 24 patients with metastatic cervical cancer were treated with a weekly bolus injection of 4'-epidoxorubicin at a dose of 12.5 mg/m2. All patients were followed until disease progression. Toxicity was generally absent or very mild. Only 1 patient (4%) had a partial remission lasting 23 weeks and 9 patients (38%) had stable disease with a median duration of 13 weeks (range 7-36). 4'-Epidoxorubicin at this dose and schedule is not active in metastatic squamous cell carcinoma of the cervix.

Phase II trial of flutamide in advanced ovarian cancer: an EORTC Gynaecological Cancer Cooperative Group study.

New active non-toxic therapeutic regimens are warranted in ovarian cancer relapsing after platinum-based chemotherapy. Some investigators have determined that androgen receptors predominated over oestrogen and progesterone receptors in untreated common epithelial ovarian cancer tissue cytosols. In an effort to test its antitumoural activity, 68 pretreated patients with epithelial ovarian cancer were given flutamide 750 mg/day orally for at least 2 months. Of 32 patients who received a minimum of 2 months of therapy, pretreated with at least one platinum-based chemotherapy, and a median of two chemotherapy regimens, two (6.3%) objective responses (one complete and one partial) and nine (28%) disease stabilisations were observed; these lasted 44 and 72 weeks, respectively (for the complete and partial response), and for a median of 24 weeks for stabilisations (range 12-48+). Nausea and vomiting were the most frequent side-effects. These occurred in 19/55 (34.5%) patients evaluable for toxicity. Flutamide has to be considered ineffective in patients extensively pretreated with chemotherapy, and it is not devoid of side-effects.

Phase II trial for intraperitoneal cisplatin plus intravenous sodium thiosulphate in advanced ovarian carcinoma patients with minimal residual disease after cisplatin-based chemotherapy--a phase II study of the EORTC Gynaecological Cancer Cooperative Group.

On the basis of its efficacy against ovarian carcinoma and its safe peritoneal administration, cisplatin administered by the intraperitoneal route was studied in a phase II multicentric trial. 34 patients with good performance status and residual disease less than 1 cm were treated with a 90 mg/m2 dose (60 mg/m2 at first cycle), administered in the abdominal cavity every 3 weeks for at least four cycles. In case of haematological or renal toxicity, intravenous sodium thiosulphate was perfused simultaneously with intraperitoneal cisplatin with protective intent. 25 patients were evaluable for response: 3 patients had pathological complete response and 1 patient had a microscopic disease (16% response rate in evaluable patients). Systemic toxicity was mild, and sodium thiosulphate clearly protected against leucopenia (6 patients) and renal toxicity (8 patients). Local side-effects were evaluable in 34 patients with 2 cases of infectious peritonitis, 1 of wound infection and 2 of haemorrhage. Of the 147 evaluable chemotherapy cycles, nine resulted in partial and one in total inflow obstruction, for which 4 patients needed surgical procedures for catheter-related complications, and 1 patient died of acute abdominal complications after such a procedure. We conclude that 90 mg/m2 intraperitoneal cisplatin has activity in pretreated patients with minimal residual disease, and that thiosulphate protects against haematological and renal toxicities. Only a randomised study can demonstrate a true benefit, which will have to be balanced with the toxicity of intraperitoneal drug administration.

Efficacy and safety of docetaxel (Taxotere) in heavily pretreated advanced breast cancer patients: the French compassionate use programme experience.

The aim of this investigation was to assess retrospectively docetaxel safety and efficacy in advanced breast cancer patients in a French compassionate use programme. Patients had received > 1 prior chemotherapy regimen for advanced disease, were either anthracycline-resistant (that is progressed within 6 months after anthracycline-based chemotherapy) or had received the maximum cumulative dose. The recommended docetaxel dose was 100 mg/m2/cycle (75 mg/m2 in case of liver function impairment: transaminases > 1.5 x upper limit of normal (ULN), alkaline phosphatases > 3 x ULN). Between August 1993 and December 1995, 889 patients were treated in 67 French centres, of whom 870 were evaluable for safety and 825 were evaluable for patient and treatment characteristics and efficacy. 20.5% (of the 825 patients evaluable for baseline characteristics) had poor performance status (PS > or = 2), 49.3% liver metastasis and 9.6% biological liver dysfunction. 98.4% had been previously treated by anthracyclines, 50.8% had resistant disease and 37.1% had received > 2 prior palliative chemotherapy lines. The most frequent severe toxicity, febrile neutropenia (reported in 223/870 (25.6%) patients evaluable for safety), caused 10 deaths, 6 of these being patients with severe liver impairment before inclusion. Fluid retention syndrome and other common non-haematological toxicities were well tolerated. 3.1% (28/889) of all patients and 11.4% of those with liver dysfunction, died from treatment-related causes. The overall response rate in 825 assessable patients was 22.9% (95% confidence interval (CI): 20.2-26.2%). Median time to treatment failure was 4 months (95% CI: 3.6-4.3) and median survival was 9.8 months (95% CI: 8.8-10.7). This report on the largest series of unselected advanced breast cancer patients treated with docetaxel, supports previous phase II studies, confirming docetaxel's utility in patients relapsing after failing anthracycline-containing palliative chemotherapy.