Hyperthermic intraperitoneal chemotherapy with oxaliplatin and without adjuvant chemotherapy in stage IIIC ovarian cancer.

OBJECTIVE: To assess the feasibility and efficacy of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) without adjuvant chemotherapy for relapsed or persistent advanced ovarian cancer. METHODS: This observational study included stage IIIC ovarian cancer patients due to undergo CRS (interval debulking or recurrent surgery) followed by HIPEC with oxaliplatin (460 mg/m2) for 30 min. RESULTS: Twenty-two patients (12 interval debulking procedures and 10 recurrence procedures) were enrolled between September 2003 and September 2007. HIPEC was not performed in four patients because of operative findings. No patient received adjuvant chemotherapy after HIPEC. Patients were followed up routinely until recurrence or death. Median peritoneal cancer index at surgery was 6 (range: 1-18). Before HIPEC, all patients had completeness of cytoreduction scores of 0 or 1. Median length of hospital stay was 21 days (range 13-65). Ten patients (55.6%) had CTCAE grade 3-4 toxicity, including three patients (16.7%) requiring reoperation. No postoperative mortality was observed. With a median follow-up of 38 months (CI 95% 23.8-39.2), median overall survival was not reached. The 3-year overall survival rate was 83% (CI 95% 54-95). Median disease-free survival was, respectively, 16.9 months (CI 95% 10.2-23.2) and 10 months (CI 95% 4.5-11.3) for patients undergoing interval debulking or recurrence surgery. CONCLUSION: HIPEC without adjuvant chemotherapy is both feasible and safe, but with a high rate of grade 3-5 toxicity. Survival results are encouraging but should be confirmed in a randomized trial.

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.

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.

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.

Docetaxel vs 5-fluorouracil plus vinorelbine in metastatic breast cancer after anthracycline therapy failure.

This multicentre, randomised phase III study compared docetaxel with 5-fluorouracil+vinorelbine in patients with metastatic breast cancer after failure of neo/adjuvant or one line of palliative anthracycline-based chemotherapy. One hundred and seventy-six metastatic breast cancer patients were randomised to receive docetaxel (100 mg m(-2)) every 3 weeks or 5-fluorouracil+vinorelbine: 5-fluorouracil (750 mg m(-2) per day continuous infusion) D1-5 plus vinorelbine (25 mg m(-2)) D1 and D5 of each 3-week cycle. Eighty-six patients received 516 cycles of docetaxel; 90 patients received 476 cycles of 5-fluorouracil+vinorelbine. Median time to progression (6.5 vs 5.1 months) and overall survival (16.0 vs 15.0 months) did not differ significantly between the docetaxel and 5-fluorouracil+vinorelbine arms, respectively. Six (7%) complete responses and 31 (36%) partial responses occurred with docetaxel (overall response rate 43%, 95% confidence interval: 32-53%), while 4 (4.4%) complete responses and 31 (34.4%) partial responses occurred with 5-fluorouracil+vinorelbine (overall response rate 38.8%, 95% confidence interval: 29-49%). Main grade 3-4 toxicities were (docetaxel vs 5-fluorouracil+vinorelbine): neutropenia 82% vs 67%; stomatitis 5% vs 40%; febrile neutropenia 13% vs 22%; and infection 2% vs 7%. There was one possible treatment-related death in the docetaxel arm and five with 5-fluorouracil+vinorelbine. In anthracycline-pretreated metastatic breast cancer patients, docetaxel showed comparable efficacy to 5-fluorouracil+vinorelbine, but was less toxic.

[Standards, options and recommendations: concomitant radiochemotherapy for cancer of the cervix: a critical analysis of the literature and update of SOR]. / Radiochimiothérapie concomitante dans les cancers du col de l'utérus: analyse critique des données et mise à jour des standards, options, et recommandations. Groupe de travail SOR.

INTRODUCTION: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the National Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres (CRLCC) and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To update, according to the methodology of SOR, the Standards, Options and Recommendations for the management of patients with cancer of the cervix, and in particular, the place of concomitant radiochemotherapy. METHODS: Data have been identified by a literature search using Medline (to April 1999) and the personal reference lists of experts. Once the guidelines were defined, the document was submitted for review to independent national and international reviewers and to the medical committees of the CRLCC. RESULTS: The principle recommendations concerning the place of radiochemotherapy in the treatment of cancer of the cervix are: 1) the available data shows a significant increase in local control (level of evidence A) and of overall survival (level of evidence B1) following concomitant radiochemotherapy as compared to radiotherapy alone or the combination of radiotherapy-hydroxyurea. For stages IB, IIA, proximal IIB with bad prognostic factors (tumour size greater than 4 cm and/or invasion of pelvic nodes and/or microscopic invasion of the parametrium) and without lumbo-aortic nodal invasion, concomitant radiochemotherapy can be considered as standard treatment. This benefit is less clear for stages distal IIB, III et IVA without para-aortic nodal invasion (level of evidence C) and must be confirmed (expert agreement); 2) the toxicity of radiochemotherapy is essentially haematologic and gastrointestinal (level of evidence B1) and is greater than that of radiotherapy alone (level of evidence B1); 3) these results have been obtained by the combination of chemotherapy based on cisplatin alone, or in combination with 5FU. Although of equal benefit, the toxicity of the cisplatin/5FU/hydroxyurea combination was greater than that of cisplatin alone in a trial comparing the two protocols. A significantly longer survival have also been obtained by the combination of chemoradiation and adjuvant chemotherapy with epirubicin (level of evidence C). These results must be confirmed; 4) the exact means of delivering the chemotherapy has not been clearly established. In fact, in these trials, some protocols use cisplatin weekly at a dose of 40 mg/m2 and others every three or four weeks at doses ranging from 50 to 75 mg/m2. Subsequent randomised studies are likely to establish optimal schema for the delivery of chemotherapy when combined with external radiotherapy and brachytherapy.