Epirubicin–vinorelbine vs FEC100 for node-positive, early breast cancer: French Adjuvant Study Group 09 trial

The aim of the study was to compare our reference adjuvant chemotherapy, FEC100 (fluorouracil 500 mg m−2, epirubicin 100 mg m−2 and cyclophosphamide 500 mg m−2, six cycles every 21 days), to an epirubicin–vinorelbine (Epi-Vnr) combination for early, poor-prognosis breast cancer patients. Patients (482) were randomised to receive FEC100, or Epi-Vnr (epirubicin 50 mg m−2 day 1 and vinorelbine 25 mg m−2, days 1 and 8, six cycles every 21 days). The 7-year disease-free survival rates were 59.4 and 58.8%, respectively (P=0.47). The relative dose intensity of planned epirubicin doses was 89.1% with FEC100 and 88.9% with Epi-Vnr. There were significantly more grades 3–4 neutropenia (P=0.009) with Epi-Vnr, and significantly more nausea-vomiting (P<0.0001), stomatitis (P=0.0007) and alopecia (P<0.0001) with FEC100. No cases of congestive heart failure were reported, whereas four decreases in left ventricular ejection fraction occurred after FEC100 and five after Epi-Vnr. One case of acute myeloblastic leukaemia was registered in the FEC100 arm. After 7 years of follow-up, there was no difference between treatment arms. Epi-Vnr regimen provided a good efficacy in such poor-prognosis breast cancer patients, and could be an alternative to FEC100, taking into account respective safety profiles of both regimens

First-line high-dose sequential chemotherapy with rG-CSF and repeated blood stem cell transplantation in untreated inflammatory breast cancer: toxicity and response (PEGASE 02 trial)

Despite the generalization of induction chemotherapy and a better outcome for chemosensitive diseases, the prognosis of inflammatory breast cancer (IBC) is still poor. In this work, we evaluate response and toxicity of high-dose sequential chemotherapy with repeated blood stem cell (BSC) transplantation administered as initial treatment in 100 women with non-metastatic IBC. Ninety-five patients (five patients were evaluated as non-eligible) of median age 46 years (range 26–56) received four cycles of chemotherapy associating: cyclophosphamide (C) 6 g m−2 – doxorubicin (D) 75 mg m−2 cycle 1, C: 3 g m−2 – D: 75 mg m−2 cycle 2, C: 3 g m−2 – D: 75 mg m−2 – 5 FU 2500 mg m−2 cycle 3 and 4. BSC were collected after cycle 1 or 2 and reinfused after cycle 3 and 4. rG-CSF was administered after the four cycles. Mastectomy and radiotherapy were planned after chemotherapy completion. Pathological response was considered as the first end point of this trial. A total of 366 cycles of chemotherapy were administered. Eighty-seven patients completed the four cycles and relative dose intensity was respectively 0.97 (range 0.4–1.04) and 0.96 (range 0.25–1.05) for C and D. Main toxicity was haematological with febrile neutropenia ranging from 26% to 51% of cycles; one death occurred during aplasia. Clinical response rate was 90% ± 6%. Eighty-six patients underwent mastectomy in a median of 3.5 months (range 3–9) after the first cycle of chemotherapy; pathological complete response rate in breast was 32% ± 10%. All patients were eligible to receive additional radiotherapy. High-dose chemotherapy with repeated BSC transplantation is feasible with acceptable toxicity in IBC. Pathological response rate is encouraging but has to be confirmed by final outcome. © 1999 Cancer Research Campaig

Differences in Efficacy and Safety of Pharmaceutical Treatments between Men and Women: An Umbrella Review

Being male or female is an important determinant of risks for certain diseases, patterns of illness and life expectancy. Although differences in risks for and prognoses of several diseases have been well documented, sex-based differences in responses to pharmaceutical treatments and accompanying risks of adverse events are less clear. The objective of this umbrella review was to determine whether clinically relevant differences in efficacy and safety of commonly prescribed medications exist between men and women. We retrieved all available systematic reviews of the Oregon Drug Effectiveness Review Project published before January 2010. Two persons independently reviewed each report to identify relevant studies. We dually abstracted data from the original publications into standardized forms. We synthesized the available evidence for each drug class and rated its quality applying the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Findings, based on 59 studies and data of more than 250,000 patients suggested that for the majority of drugs no substantial differences in efficacy and safety exist between men and women. Some clinically important exceptions, however, were apparent: women experienced substantially lower response rates with newer antiemetics than men (45% vs. 58%; relative risk 1.49, 95% confidence interval 1.35–1.64); men had higher rates of sexual dysfunction than women while on paroxetine for major depressive disorder; women discontinued lovastatin more frequently than men because of adverse events. Overall, for the majority of drugs sex does not appear to be a factor that has to be taken into consideration when choosing a drug treatment. The available body of evidence, however, was limited in quality and quantity, confining the range and certainty of our conclusions

Monocentric retrospective analysis of locally advanced and inflammatory breast cancer (IBC) patients (pts) having received a neoadjuvant chemotherapy with docetaxel (D) and anthracyclines

10743 Background: Anthracycline-based neoadjuvant therapy is a standard treatment, but use of D in the preoperative setting increases clinical and pathological response, as monotherapy or as part of combination chemotherapy for preoperative setting. Our purpose was to assess the efficacy in pts who were treated with D and anthracyclines (doxorubicine A or epirubicine E) in neoadjuvant setting. Methods: Pts with histologically proven, unilateral breast cancer, T2-T4, N0-N2, M0 tumors received every 3 weeks an association of D and A or E, according to different schedules. This retrospective analysis was designed to evaluate the clinical and pathological response rate of this association. Results: Between October 1999 and December 2003 45 pts (44 women and 1 man) were treated with associations: 39 D and E or A, 3 D, A and vinorelbine, 1 D, A and capecitabine (X), 1 D, A and trastuzumab (H), 1 D, X and H; median age 47 [27–71] years; median number of cycles of chemotherapy: 4 [3–6]; median tumour diameter: 50 mm [20–150] with 6 IBC; median radiological size: mammography 32 mm [11–90], echography 32.5 mm [8–90]; tumour stage: 15 T2N0 (33%), 12 T2N1 (27%), 7 T3N0 (15%), 2 T3N1 (4%), 1 T3N2 (2%), 1 T4bN1 (2%), 1 T4cN2 (2%), 3 T4dN0 (7%), 2 T4dN2 (4%), 1 T4N0 (2%); tumour grade: 22 grade II (49%), 22 grade III (49%), 1 unknown; tumour histology : 31 ductal carcinoma (69%), 13 lobular carcinoma (29%), 1 mucineous carcinoma (2%); hormonal status: 29 positive (64%), 16 negative (36%). Among these pts, 13 had nodal curage concomitant with diagnosis biopsy. All pts were evaluable for clinical response: ORR was 91% (18 complete response CR 40%, 23 partial response PR 51%. Histological response was available in 32 pts: Chevallier classification pCR grade 1–2: 5 (11%), Sataloff TA /NA-NB 5 (16%). On 32 pts with postchemotherapy nodal curage, 16 had negative nodal disease. On these 16 pts, 8 were N0 at diagnosis, 5 N1 and 3 N2. Conclusions: Association of D and anthracyclines in breast carcinoma exhibits a high pathological response rate. No significant financial relationships to disclose. </jats:p

Capecitabine + epirubicin + cyclophosphamide (CEX) has comparable safety to 5-FU + epirubicin + cyclophosphamide (FEC) as neoadjuvant therapy in patients (pts) with operable breast cancer (BC): Early safety findings from a randomized phase III trial

10655 Background: FEC100 is an established regimen in early-stage BC. Substituting capecitabine (X) for 5-FU in the neoadjuvant setting is logical. Here we present interim safety findings from a phase III trial of CEX vs. FEC as neoadjuvant chemotherapy in operable BC. Methods: Between Mar 04 and Jan 05, 60/182 planned pts were randomized to receive CEX (X 900mg/m2 bid d1–14, epirubicin 100mg/m2 and cyclophosphamide 500mg/m2 d1) or FEC (short i.v. infusions of 5-FU 500mg/m2, epirubicin 100mg/m2 and cyclophosphamide 500mg/m2 d1), q3w x4. Surgery with lymph node dissection was performed &lt;5 wks (±1 wk) after last course of treatment. The primary endpoint was pCR. All patients received 4 courses of docetaxel 100 mg/m2 d1 after surgery. All adverse events (AEs) were graded according to the NCI-CTC (v3.0) and the Hand-Foot Syndrome (HFS) classification. Peripheral blood mononuclear cells (PBMC) were evaluated for dihydropyrimidine deshydrogenase (DPD) deficiency. Results: Baseline characteristics in the CEX (n = 30) vs. FEC (n = 30) groups: median age (49.1 vs. 50.8 years); ER+/PR+ (60%/53% vs. 73%/37%). The median no. of cycles received was 4 in each group. The overall rate of AEs was very similar in the two groups, with no difference in grade 3/4 neutropenia. FEC was associated with more grade 3/4 nausea/vomiting (see table) . No evidence of PBMC DPD deficiency was observed. Conclusions: CEX and FEC are well tolerated in neoadjuvant BC. CEX offers the potential benefit of greater tumor exposure to 5-FU. Our findings also indicate that toxicity is not related to DPD activity. Recruitment is ongoing. [Table: see text] [Table: see text] </jats:p

Epoetin beta treatment of chemotherapy induced anemia in cancer patients: Results of a large prospective cohort study

19582 Background: The efficacy of epoetin beta (E) is well documented in clinical trials in anemic cancer patients (pts). This study was conducted to assess E use, efficacy, safety and effect on quality of life in cancer pts, in usual practice. Methods: This prospective, multicenter, longitudinal, observational French study assessed a 4-month follow-up of informed consent cancer pts (including both solid tumors (ST) and hematological malignancies (H)) treated with E for chemotherapy-related anemia. Data were collected between January 2005 and March 2006. Results: Among 3100 pts enrolled by 423 specialists, 2810 were analysed. Pts’ characteristics were: mean age 63±13 yrs, male 50%, performance status 0 (13%), 1 (46%), =2 (41%). 74% of pts suffered from a ST and 26% from a H. The most frequent cancer types were lung (22%), breast (15%), non-Hodgkin lymphoma (12%), colon (9%), multiple myeloma (7%), ovary (7%), prostate (3%), head and neck (3%) and chronic lymphocytic leukemia (3%). The mean time from diagnosis to inclusion was 2 yrs. 52% of pts received their first line of chemotherapy, 25% their second one. 55% and 10% of ST and H pts received platinum based regimen, respectively. At inclusion, hemoglobin levels were distributed as follows: &lt; 9 g/dl (ST 14%, H 32%), [9–11 [g/dl (ST 70%, H 56%), [11–13 [g/dl (ST 16%, H 11%). Regarding pre-treatment biological tests, endogenous erythropoietin rate was controlled for only 3% of pts (ST 1% and H 7%, median 37 IU/ml [0; 388]), ferritin was available for 15% of pts (ST 11% and H 28%), transferrin saturation for 12% of pts (ST 10% and H 17%) and reticulocytes for 11% of pts (ST 7% and H 24%). At initiation, pts received a median dose of 30000 U/week of E on a once weekly regimen schedule for 98% of pts. E was associated with iron supplementation in 49% and 13% of ST and H pts, and with blood transfusion in 5% and 15% of ST and H pts. Conclusion: These preliminary results describe baseline characteristics of cancer patients treated with epoetin beta. The study suggests very few biological controls before initiation of E in routine practice. Final analyses of hemoglobin evolution and quality of life will be presented. [Table: see text] </jats:p