A phase II study of high-dose epirubicin in ovarian cancer patients previously treated with cisplatin

Background; In vitro data demonstrated a dose-response relationship for doxorubicin in ovarian cancer cell lines. However, this dose-response question for anthracyclines has never been adequately addressed in ovarian cancer patients. A phase I study with epirubicin gave support to these in vitro findings and recommended a dose of 150 mg/m2 for phase II testing. Patients and methods: The present report concerns the final analysis of an EORTC-Gynecological Cancer Cooperative Group (GCCG) phase II study of high-dose epirubicin (HDE) in cisplatin-pretreated patients with epithelial ovarian cancer. A total of 100 eligible patients were included; 34 had progressed during first-line therapy (group 1), 17 had persistent disease after first-line therapy (group 2) and 49 had relapsed following an initial response to first-line therapy (group 3). All patients had measurable or evaluable disease, were aged < 75 years, had a WHO performance status 0-2, had adequate vital organ function and gave consent. Epirubicin was administered by rapid i.v. infusion at a dose of 150 mg/m2 and given at threeweek intervals. Escalation to 180 mg/m2 was to be carried out if white blood cell nadir count was >2.0 x 109/l and platelet nadir count was > 75 x 109/l. Results: A total of 361 HDE treatment cycles were administered, the median number per patient being 4. Of the 85 patients who received at least two cycles of protocol treatment, 26 (31%) did not have any dose modification, 23 (26%) had dose reduction, while 36 (43%) had the dose increased to 180 mg/m2, at least for one cycle. The response rate in all eligible patients was 20% (95% confidence interval 13%-30%), 15% in group 1, 12% in group 2 and 27% in group 3. Patients with a cisplatin-free interval of > 12 months responded in 41%. The median duration of response was nine months (range 19 weeks to 3 years). Main toxicities were myelosuppression (leucopenia, neutropenia), nausea, vomiting, alopecia and mucositis. There were three cases of excessive toxicity leading to early discontinuation of HDE treatment and in one patient this contributed to death. No serious cardiotoxicity was recorded. Conclusions: It is concluded that HDE is active in platinumpretreated patients with epithelial ovarian cancer and should be further studied in first-line in combination with paclitaxel and a platinum compound

Climate change effects on snow melt and discharge of a partly glacierized watershed in Central Switzerland (SoilTrec Critical Zone Observatory)

A comprehensive hydrological modeling study in the drainage area of a hydropower reservoir in central Switzerland is presented. Two models were tested to reproduce the measured discharge dynamics: (1) a detailed energy-balance model (ALPINE3D) primarily designed for snow simulations; (2) a conceptual runoff model system (PREVAH), including a distributed temperature-index snow and ice melt model. Considerable effort was put into distributing available meteorological station data to the model grids as forcing data. The recent EU regional climate modeling initiative ENSEMBLES provided up-to-date climate predictions for two 30-a periods in mid and late 21st century. These were used to estimate evolutions in the water supply of the hydropower reservoir in response to expected climate changes. The simulations suggest a shift of spring peak-flow by almost two months for the end of the century. Warmer winter temperatures will cause higher winter base-flow. Due to glacier retreat, late-summer flow will decrease at the end of the century

Toxicity at three years with and without irradiation of the internal mammary and medial supraclavicular lymph node chain in stage i to III breast cancer (EORTC trial 22922/10925)

Introduction. The EORTC 22922/10925 trial investigated the potential survival benefit and toxicity of elective irradiation of the internal mammary and medial supraclavicular (IM-MS) nodes Accrual completed in January 2004 and first results are expected in 2012. We present the toxicity reported until year 3 after treatment. Patients and methods. At each visit, toxicity was reported but severity was not graded routinely. Toxicity rates and performance status (PS) changes at three years were compared by χ2 tests and logistic regression models in all the 3 866 of 4 004 patients eligible to the trial who received the allocated treatment. Results. Only lung (fibrosis; dyspnoea; pneumonitis; any lung toxicities) (4.3% vs. 1.3%; p < 0.0001) but not cardiac toxicity (0.3% vs. 0.4%; p = 0.55) significantly increased with IM-MS treatment. No significant worsening of the PS was observed (p = 0.79), suggesting that treatment-related toxicity does not impair patient's daily activities. Conclusions. IM-MS irradiation seems well tolerated and does not significantly impair WHO PS at three years. A follow-up period of at least 10 years is needed to determine whether cardiac toxicity is increased after radiotherapy

Phase II study of a combination of cyclophosphamide, adriamycin and cisplatin in advanced fallopian tube carcinoma. An EORTC gynecological cancer group study. European Organization for Research and Treatment of Cancer.

Item does not contain fulltextOBJECTIVE: To investigate the clinical activity and toxicity of a combination chemotherapy consisting of cyclophosphamide (C), adriamycin (A) and cisplatin (P) for patients with primary adenocarcinoma of the Fallopian tube having FIGO stage III-IV disease. METHODS: The CAP-regimen consisted of cyclophosphamide 600 mg/m2, adriamycin 45 mg/m2, and cisplatin 50 mg/m2 administered intravenously on day one every 28 days. RESULTS: Twenty-four eligible patients with histologically-confirmed Fallopian tube adenocarcinoma were entered in the trial. Fourteen patients had FIGO stage III, and ten had stage IV disease. The median number of CAP cycles was six. Ten patients had a complete and six had a partial response (response rate: 67%, 95% confidence limits: 45-84%). WHO grade III-IV side-effects included haematological toxicity, nausea/vomiting and alopecia. Furthermore, mild signs of cisplatin-related peripheral neurotoxicity were observed. At a median follow-up of 40 months, nine patients were alive and 15 had died due to malignant disease. The median time to progression was 13 months for all patients. The median overall survival was 24 months and the 1-, 3- and 5-year survival and their 95% confidence limits were 73% (54-92%), 25% (4-46%) and 19% (0-38%), respectively. CONCLUSION: The present data confirm the therapeutic activity of the CAP-regimen in primary Fallopian tube adenocarcinoma. The response rate is moderate and the toxicity profile is acceptable