A phase III adjuvant randomised trial of 6 cycles of 5-fluorouracil-epirubicine-cyclophosphamide (FEC100) versus 4 FEC 100 followed by 4 Taxol (FEC-T) in node positive breast cancer patients (Trial B2000).

BACKGROUND: Standard adjuvant chemotherapy regimens for patients with node positive (N+) breast cancer consisted of anthracycline followed by taxane. The European Association for Research in Oncology embarked in 2000 on a phase III trial comparing 6 cycles of FEC100 versus 4 FEC100 followed by 4 Taxol. Primary end-point was disease free survival. Secondary end-points were overall survival, local recurrence free interval, metastases free interval and safety. PATIENTS AND METHODS: Between March 2000 and December 2002, 837 patients were randomised between 6FEC100 for 6 cycles (417patients) or FEC100 for 4 cycles then Taxol 175mg/m(2)/3 weeks for 4 cycles (4FEC100-4T) (420 patients). One thousand patients had been planned initially but the trial was closed earlier due to slow accrual. RESULTS: Hazard ratios (HRs) were 0.99 for disease-free survival (DFS) (95%CI: 0.77-1.26; p=0.91), and 0.85 for overall survival (OS) (95%CI: 0.62-1.15; p=0.29). Nine-year DFS were 62.9% versus 62.5% for 6FEC100 and 4FEC100-4T, respectively. Nine-year OS were 73.9% versus 77% for 6FEC100 and 4FEC100-4T, respectively. Toxicity analyses based on 803 evaluable patients showed that overall grade 3-4 toxicities were similar in both arms (63% versus 58% for 6FEC100 arm and 4FEC100-4T arm, respectively; p=0.16). CONCLUSION: In this trial replacing the last 2 FEC100 cycles of 6FEC100 regimen by 4 Taxol does not lead to a discernable DFS or OS advantage. The lack of a significant difference between the randomised treatment arms may however be due to a lack of power of this trial to detect small, yet clinically worthwhile, treatment benefits.

High rate of extra-haematological toxicity compromises dose-dense sequential adjuvant chemotherapy for breast cancer.

BACKGROUND: A dose-dense strategy has been considered to improve results of adjuvant chemotherapy for breast cancer. This randomised phase II trial investigated the feasibility of this approach with sequential anthracyclines and taxanes-based chemotherapy. METHODS: Patients with high-risk node-positive breast cancer were treated with three cycles of fluorouracil 500 mg m(-2), epirubicin 100 mg m(-2), cyclophosphamide 500 mg m(-2) (FEC 100) followed by three cycles of docetaxel 100 mg m(-2) delivered at 2-weekly intervals supported by primary prophylaxis with filgrastim. All patients were randomised to either uninterrupted treatment (arm A) or to have a 2-week additional period of rest between the FEC and docetaxel (arm B). The primary endpoint was the rate of success of chemotherapy delivery. Using a two-stage Fleming design, 120 patients were required with one interim analysis. RESULTS: In March 2005, enrolment was stopped into arm A after the observation of severe skin toxicities. Following the planned interim analysis, the study was closed because of the high rate of grade 3/4 skin toxicities in both arms (arm A: 32.4% and arm B: 18.9%). CONCLUSION: Sequential dose-dense FEC 100 followed by docetaxel 100 mg m(-2) is not feasible. Feasibility still depends largely on several factors including the choice of drugs, dosage and sequence of administration.

Complete hormonal blockade versus epirubicin-based chemotherapy in premenopausal, one to three node-positive, and hormone-receptor positive, early breast cancer patients: 7-year follow-up results of French Adjuvant Study Group 06 randomised trial.

BACKGROUND: The purpose of this study was to determine optimal adjuvant therapy between complete hormonal blockade in premenopausal patients with hormone receptor positive breast cancer and one to three positive nodes. PATIENTS AND METHODS: We randomised 333 patients to receive either LHRH agonist (triptorelin 3.75 mg i.m., monthly) plus tamoxifen 30 mg/day for 3 years (TAM-LHRHa, n=164), or fluorouracil 500 mg/m2, epirubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 21 days for six cycles, without any hormonal treatment (FEC50, n=169). RESULTS: The 7-year disease-free survival (DFS) was 76% with TAM-LHRHa, and 72% with FEC50 (P=0.13). The 7-year overall survival (OS) was 91% and 88%, respectively (P=0.20). The multivariate analysis confirmed that both treatments were not different for DFS and OS (P=0.83 and P=0.41, respectively). Amenorrhoea occurred in 64% of patients treated with FEC50; it was temporary in 58% of cases after hormonotherapy and in 31% after chemotherapy. CONCLUSION: In intermediate-risk breast cancer, complete hormonal blockade and chemotherapy provided similar outcomes. Hormonal treatment is an alternative to chemotherapy in hormone-sensitive patients, considering the preference of patients in terms of quality of life.

'Parcours de Femme 2001': a French opinion survey on overall disease and everyday life management in 1870 women presenting with gynecological or breast cancer and their caregivers.

PURPOSE: The aim of the survey 'Parcours de Femmes 2001' was to evaluate the overall management and care of women with female cancers and to determine their needs. METHODS: Women with breast or gynecological cancer who had either received at least 3 months of treatment or had completed treatment <1 year before the study were enrolled in this cross-sectional, observational study. RESULTS: From February to November 2001, 2839 questionnaires were distributed; 1870 were returned (66% response rate), mainly by breast cancer patients (87%). While 92% of women reported having received information at diagnosis, 34% of relapsed patients complained of lack of information concerning their disease and treatment. Only 18% of patients were included in the treatment decision process and 66% of women obtained complementary information from the media, patients and care professionals. Fatigue was the most severe problem quoted (78% of cases) and was poorly managed by caregivers due to diagnostic and treatment difficulties. Problems relating to family and to affective and socio-professional life were poorly identified and remained largely unmanaged. CONCLUSIONS: Information given to female cancer patients must be improved in relapsed patients, particularly regarding the adverse effects of treatment. Psychosocial management requires a more holistic approach through new channels, together with the coordination of existing structures.

Results of a phase III prospective, randomised trial, comparing mitoxantrone and vinorelbine (MV) in combination with standard FAC/FEC in front-line therapy of metastatic breast cancer.

This comparative phase III trial of mitoxantrone+vinorelbine (MV) versus 5-fluorouracil+cyclophosphamide+either doxorubicin or epirubicin (FAC/FEC) in the treatment of metastatic breast cancer was conducted to determine whether MV would produce equivalent efficacy, while resulting in an improved tolerance in relation to alopecia and nausea/vomiting. This multicentre study recruited and randomised 281 patients with metastatic breast cancer; 280 were evaluable for response survival and toxicity (138 received FAC/FEC, 142 received MV). Patient characteristics were matched in each arm and stratification for prior exposure to adjuvant therapy was made prospectively. The overall response rate (ORR) was equivalent in the two arms (33.3% for FAC/FEC versus 34.5% for MV), but MV was more effective in patients who had received prior adjuvant therapy (13% (95% confidence interval (CI) 3-23) for FAC/FEC versus 33% (95% CI 20-47) for MV P=0.025) with a better progression-free survival (PFS) (5 months (range 1-18 months) versus 8 months (range 1-27 months); P=0.0007 for FAC/FEC versus MV, respectively) while FAC/FEC was more effective in previously untreated patients (ORR 43% (95% CI 33-53) versus 35% (95% CI 25-45), P=0.26; PFS 9 months (range 0-29 months) versus 6 months (range 0-26 months) P=0.014). Toxicity was monitored through the initial six cycles of therapy; febrile neutropenia and delayed haematological recovery was more frequent for MV (P=0.001), while nausea/vomiting of grades 3-4 was greater for FAC/FEC (P=0.031), as was alopecia (P=0.0001), cardiotoxicity was the same for the two regimens. MV represents a chemotherapy combination with equivalent efficacy to standard FAC/FEC and improved results for patients who have previously received adjuvant chemotherapy. Toxicity must be balanced to allow for increased haematological suppression and risk of febrile neutropenia with MV compared with a higher risk of subjectively unpleasant side-effects such as nausea/vomiting and alopecia with FAC/FEC.

[Adjuvant combined radiochemotherapy: a feasibility study of a new strategy in stages I and II]. / Traitement adjuvant des cancers du sein par radiochimiothérapie concomitante: étude de faisabilité d'une nouvelle alternative stratégique dans les stades I et II.

Adjuvant radiotherapy is the rule after conservative surgery for breast cancer. Furthermore, an anthracycline-based chemotherapy is recommended in node-positive patients and in poor prognosis tumors. The optimal schedule of treatment has yet to be determined, but ideally, none of these therapeutic modalities should be delayed. We have therefore conducted a feasibility trial using post-operative concurrent chemoradiation therapy with an anthracenedione. Between May 1990 and October 1994, 154 patients with stage I or II breast cancer who had benefited of either limited or radical surgery were treated with adjuvant concurrent chemoradiotherapy. Radiotherapy consisted of 50 Gy in 25 fractions over 5 weeks to the chest wall or the breast, and to the supraclavicular and internal mammary lymph nodes. When indicated, a boost of 15 Gy was then delivered to the primary tumor bed (n = 75). Starting on the first week of radiotherapy, combined chemotherapy with 5-fluorouracil, mitoxantrone, and cyclophosphamide was administered at 21-day intervals, for 4 to 6 cycles. Compliance to therapy was excellent. Median radiotherapy dose was 49.5 Gy to the chest wall or breast, and to the lymph nodes, and 14.2 Gy to the tumor bed. Chemotherapy was given at full dose in over 80% of the cases and the 21-day interval between cycles was respected in 31%. In 45% of the cases, a 28-day interval was required due to toxicity, and at least one interval longer than 28 days was necessary in the remainder of the patients. Main toxicities were nausea and vomiting (20.8%) and grade 3-4 neutropenia (12.3%). Grade 1 cutaneous toxicity occurred in 62.3% of the cases, and severe grade 3 radiation dermatitis requiring temporary interruptions of therapy in 4.5%. With the exception of one case of grade 3 acute cardiac toxicity, there was no other severe side-effects. In conclusion, this pilot study demonstrates the feasibility of concurrent chemoradiation therapy with an anthracenedione for stage I and II breast cancer in the adjuvant setting. Whether this approach compares favorably with standard sequential therapy in terms of long-term results remains to be determined and should be assessed in a phase III trial.

[Lymphoscintigraphic aspects of the effects of manual lymphatic drainage]. / Aspects lymphoscintigraphiques des effets du drainage lymphatique manuel.

Manual lymphatic drainage is used in physiotherapy of limb lymphedema in combination with other physical techniques. In order to assess the effectiveness of the method, 47 patients with upper limb lymphedema after radiosurgical therapy for breast cancer underwent lymphoscintigraphy. The examination was performed after subcutaneous injection of technetium-labeled colloid via the fourth and first interdigital space on the hand of the limb with lymphedema. The level of the technetium label was compared on scintigraphies performed before and after manual lymph drainage. Results were analyzed as a function of the clinical characteristics of the edema. Manual lymphatic drainage produced an effective progression of the label in 25 cases (53.2%), independent of radiotherapy. Contralateral lymph nodes were reached in 5 cases and the homolateral internal mammary nodes in 2. These nodes were visualized only after manual lymphatic drainage. The visualization of the drainage routes in unexpected areas demonstrated the effectiveness of the technique in stimulating accessory routes useful for resorption of lymphedema. The use of two injection sites on the hand is also discussed. This study demonstrated the effect on a single session of manual lymphatic drainage and should be completed with an assessment of a complete series of manual lymphatic drainages.

Postmenopausal patients with node-positive resectable breast cancer. Tamoxifen vs FEC 50 (6 cycles) vs FEC 50 (6 cycles) plus tamoxifen vs control--preliminary results of a 4-arm randomised trial. The French Adjuvant Study Group.

In 1986 the true benefit of adjuvant medical treatment in postmenopausal patients with pathological node-positive breast adenocarcinoma was still controversial. The French Adjuvant Study Group (FASG) initiated a randomised trial to elucidate the respective roles of adjuvant chemo-and/or hormonotherapy in this group of patients. Of the 776 patients who have been included between 1986 and 1990, 741 were fully eligible for evaluation. Inclusion criteria were postmenopausal patients aged between 50 and 70 years with adenocarcinoma of the breast, positive pathological nodes and no distant metastasis. Patients were randomised to 1 of 4 treatment arms: Group A (n = 192) received tamoxifen 30 mg/day orally for 3 years; Group B (n = 183) received FEC 50 (fluorouracil 500 mg/m2, epirubicin 50 mg/m2 plus cyclophosphamide 500 mg/m2) for 6 cycles; Group C (n = 182) received tamoxifen 30 mg/day orally for 3 years plus FEC 50 for 6 cycles; Group D (n = 184) received no medical adjuvant treatment. Surgery was either modified radical mastectomy (n = 363) or tumorectomy (n = 378), and postoperative irradiation was given to all patients. All major prognostic factors were well balanced between the 4 patient groups. Toxicity was evaluated in 348 patients in Groups B and C who received a total of 1983 chemotherapy cycles. Median epirubicin dose intensity (mg/m2/week) was 15.8 in Group B and 15.7 in Group C. Grade 3 to 4 neutropenia was observed in 4.7% of cycles for Group B and 3.7% for Group C. Grade 3 to 4 nausea/vomiting were seen in 18% of treatment cycles in Group B and 15% in Group C.(ABSTRACT TRUNCATED AT 250 WORDS)

[Current role of chemotherapy in the treatment of invasive cancers of the bladder]. / Place actuelle de la chimiothérapie dans le traitement des cancers infiltrants de vessie.

Treatment of bladder carcinoma with cystectomy and or radiotherapy provide 5-year survival rates of 28-50%. Phase II chemotherapy trials have proven its efficacy with a partial and complete response rate of 20% and 10% respectively for drugs such as cisplatin or methotrexate. Recent phase III studies have demonstrated the superiority of associations such as CMV, CISCA or M-VAC with complete response rates of 28-39%. Neoadjuvant chemotherapy may increase local control and offer the possibility of conservative treatment after complete tumor regression (one third of cases). The positive effect of neoadjuvant chemotherapy on survival has not yet been demonstrated and randomized trials are now in progress. The concomitant association of cisplatin or fluorouracil with radiation therapy provides high complete response rates (65-88%) in all published studies. A longer follow-up period is necessary to confirm these results in terms of local control gain and survival benefit, but this strategy seems to constitute a major advancement for patients unable to undergo radical cystectomy. Further studies are needed before extending this conservative approach to less advanced invasive bladder carcinoma. Adjuvant chemotherapy may decrease metastasis rate, but survival benefit has not yet been definitively established by randomized studies.

[ A comparative lympho-scintigraphic evaluation of manual lymphatic drainage and pressotherapy in edema of the arm following treatment of a breast tumor]. / Evaluation comparative lymphoscintigraphique du drainage lympathique manuel et de la pressothérapie sur l'oedème du membre supérieur secondaire au traitement d'une tumeur mammaire.

Manual lymphatic drainage (MLD) and pressure-therapy are part of the therapeutical gears used in physiotherapy for reducing edema. The solution to the problem of the reduction fo lymphedema of the extremities rests with the evacuation of the liquid phase and the resorption of the stagnant proteins in the interstitial compartment not being collected by the lymphatic system. The injection of a 99 Technetium-labelled colloid substance provides a functional approach to the problem of lymphatic stasis.

[Combination radiotherapy and chemotherapy in cancer of the pancreas. Review of the literature and prospects]. / Les associations radio-chimiothérapiques dans le cancer du pancréas. Revue de la littérature et perspectives.

Overall prognosis of pancreatic adenocarcinoma is still very poor with median survival around 10 months after radical surgery in operable patients, or after full-dose radiation therapy in non-surgical candidates. In metastatic disease, multidrug chemotherapy regimens give a response rate of around 30% with median survival of 10 months. Random trials conducted by the GITSG in inoperable cases have shown improved results for chemoradiation with 5-FU for radiotherapy alone and a doubling of median survival with a 1-year survival of 40% vs 10%. Incorporation of Adriamycin in these combined modality protocols does not improve the results in terms of survival. Chemoradiation also shows improved results compared with chemotherapy alone. In patients amenable to radical surgery, adjuvant post-operative treatment with chemoradiation gave superior results over surgery alone with a doubling of median survival and a significant improvement of a two-year survival rate (42% versus 15%). Intra-operative radiation therapy leads to better local control but without a significant improvement in survival. With a better understanding of radio-chemotherapy interactions and mechanisms of radiosensitization through continuous infusion of fluorouracil and/or cisplatinum, these encouraging results should be confirmed within the next few years.