Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group

Background: Combination chemotherapy yields better response rates which do not always lead to a survival advantage. The aim of this study was to investigate whether the reported differences in the efficacy and toxicity of monotherapy with doxorubicin (DOX) versus combination therapy with cisplatin (CDDP) in endometrial adenocarcinoma lead to significant advantage in favour of the combination. Patients and methods: Eligible patients had histologically-proven advanced and/or recurrent endometrial adenocarcinoma and were chemo-naïve. Treatment consisted of either DOX 60 mg/m2 alone or CDDP 50 mg/m2 added to DOX 60 mg/m2, every 4 weeks. Results: A total of 177 patients were entered and median follow-up is 7.1 years. The combination DOX-CDDP was more toxic than DOX alone. Haematological toxicity consisted mainly of white blood cell toxicity grade 3 and 4 (55% versus 30%). Non-haematological toxicity consisted mainly of grade 3 and 4 alopecia (72% versus 65%) and nausea/vomiting (36 % versus 12%). The combination DOX-CDDP provided a significantly higher response rate than single agent DOX (P <0.001). Thirty-nine patients (43%) responded on DOX-CDDP [13 complete responses (CRs) and 26 partial responses (PRs)], versus 15 patients (17%) on DOX alone (8 CR and 7 PR). The median overall survival (OS) was 9 months in the DOX-CDDP arm versus 7 months in the DOX alone arm (Wilcoxon P = 0.0654). Regression analysis showed that WHO performance status was statistically significant as a prognostic factor for survival, and stratifying for this factor, treatment effect reaches significance (hazard ratio = 1.46, 95% confidence interval 1.05-2.03, P = 0.024). Conclusions: In comparison to single agent DOX, the combination of DOX-CDDP results in higher but acceptable toxicity. The response rate produced is significantly higher, and a modest survival benefit is achieved with this combination regimen, especially in patients with a good performance statu

Neoplastic pericardial disease in lung cancer: impact on outcomes of different treatment strategies. A multicenter study.

none17Background: Local (intrapericardial) chemotherapy has been reported to be useful for the treatment of neoplastic pericardial disease, but it has never been compared to systemic chemotherapy, a combination of the two and simple pericardial drainage or sclerosis. Methods: We analyzed the clinical and echocardiographic data of 119 patients, suffering of neoplastic pericarditis due to lung cancer (97 with non-small-cell), comparing the outcomes of four different treatment strategies (extended catheter drainage/sclerosis, systemic chemotherapy, local chemotherapy, and combined - local plus systemic - chemotherapy) at the last available follow-up or at the change of therapy after a treatment failure. The outcomes (based on semiquantitative evaluation of pericardial disease) were classified as complete, partial, no response and progressing disease. Results: A complete response was achieved in 37/53 of patients with combined, in 12/22 with local, in 5/27 with systemic chemotherapy, respectively, and in 4/17 after drainage/sclerosis (p<0.001). Overall response was achieved in 51/53 with combined, 18/22 and 16/27 with local or systemic chemotherapy, respectively, and in 5/17 with drainage/sclerosis only (p<0.001). Survival was significantly better after combined chemotherapy (p<0.001) and 12/53 patients (23%) in this subgroup survived more than 1 year. The overall response rate was higher with intrapericardial cisplatinum than with other agents (98% vs 80%, χ2=7.69, p<0.01). Conclusions: Local chemotherapy, alone or with systemic chemotherapy, is effective in treating pericardial metastases from lung carcinoma, leading to a good control of pericardial effusion in 92% of cases, and to complete disappearance of effusion and masses in 65%. Combined therapy is significantly better than any other treatment. Pericardiocentesis and intrapericardial chemotherapy should be used whenever possible in lung cancer neoplastic pericardial disease, not only in case of tamponade.Lestuzzi C;Bearz A;Lafaras C;Gralec R;Cervesato E;Tomkowski W;DeBiasio M;Viel E;Bishiniotis T;Platogiannis DN;Buonadonna A;Tartuferi L;Piazza R;Tumolo S;Berretta M;Santini F;Imazio MLestuzzi, C; Bearz, A; Lafaras, C; Gralec, R; Cervesato, E; Tomkowski, W; Debiasio, M; Viel, E; Bishiniotis, T; Platogiannis, Dn; Buonadonna, A; Tartuferi, L; Piazza, R; Tumolo, S; Berretta, M; Santini, Francesco; Imazio, M

Medulloblastoma variants: Age-dependent occurrence and relation to gorlin syndrome-a new clinical perspective

Purpose: We aimed to test the hypothesis that medulloblastoma (MB) variants show a different age distribution and clinical behavior reflecting their specific biology, and that MB occurring at very young age is associated with cancer predisposition syndromes such as Gorlin syndrome (GS). Experimental Design: We investigated the frequency, age distribution, location, response to treatment, outcome, and association with familial cancer predisposition syndromes in a series of 82 cases of MB in patients ages <14 years diagnosed at the Giannina Gaslini Children's Hospital, Genoa, between 1987 and 2004. Results: Desmoplastic MB and MB with extensive nodularity (MBEN), were present in 22 of 82 cases (27%) and were more frequent in children ages ≤3 years (13 of 25; 52%). In this age group, MBEN was significantly more frequent than desmoplastic MB and classic MB (P < 0.001) and had a good prognosis. MBEN was associated with GS in 5of 12 cases. Overall, 8 cases occurred in the context of familial tumor predisposition syndromes (5GS, 1 each NF1, Li- Fraumeni, and Fragile X) and 7 of these patients were ages ≤3 years at diagnosis. Desmoplastic histology and a more intensive treatment represented independent favorable prognostic factors in multivariate analysis (P = 0.003 and P = 0.0139, respectively). Metastasis was a predictor of bad outcome (P = 0.0001). Conclusions: Our data indicate that biologically different MB entities warrant risk-adapted treatment and that MBEN is strongly associated with GS. Patients, ages ≤3years, with MB and their families should be investigated for tumor predisposition syndromes such as GS. © 2009 American Association for Cancer Research

Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial

Background Previously, we have shown that the combination of cyclophosphamide, doxorubicin, and cisplatin (CAP) and single-agent carboplatin produce similar survival and progression-free survival rates in women with ovarian cancer. Subsequently, paclitaxel combined with platinum has become a widely accepted treatment for the disease. We aimed to compare the safety and efficacy of paclitaxel plus carboplatin with a control of either CAP or carboplatin alone.Methods Between February, 1995, and October, 1998, we enrolled 2074 patients from 130 centres in eight countries. Women were randomly assigned paclitaxel plus carboplatin or control, the control (CAP or single-agent carboplatin) being chosen by the patient and clinician before randomisation. The primary outcome measure was overall survival. Secondary outcomes were progression-free survival and toxicity. Analysis was by intention to treat.Findings With a median follow-up of 51 months, 1265 patients had died, and survival curves showed no evidence of a difference in overall survival between paclitaxel plus carboplatin and control (hazard ratio 0.98, 95% Cl 0.87-1.10, p=0.74). The median overall survival was 36.1 months on paclitaxel plus carboplatin and 35.4 months on control (difference 0.7 months, 95% CI -3.6 to 4.7). 1538 patients had progressive disease or died, and again, Kaplan-Meier curves showed no evidence of a difference between the groups (hazard ratio 0.93, 95% Cl 0.84-1.03, p=0.16). Median progression-free survival was 17.3 months on paclitaxel plus carboplatin and 16.1 months on control (difference 1.2 months, 95% Cl -0.5 to 2.8). Paclitaxel plus carboplatin caused more alopecia, fever, and sensory neuropathy than carboplatin alone, and more sensory neuropathy than CAP. CAP was associated with more fever than paclitaxel plus carboplatin.Interpretation Single-agent carboplatin and CAP are as effective as paclitaxel plus carboplatin as first-line treatment for women requiring chemotherapy for ovarian cancer. The favourable toxicity profile of single-agent carboplatin suggests that this drug is a reasonable option as first-line chemotherapy for ovarian cancer

Choice or necessity? A review of the role of DIY in tackling housing repair and maintenance

Do-it-yourself (DIY) is a staple element of the spare time activities of many households, but little is known about the extent to which basic repair work is carried out through DIY and about the quality of this work. Through secondary analyses of UK government data (English House Condition Survey and Family Expenditure Survey), this paper examines the scale of DIY work by owner-occupiers, how work is organized, the interrelationship of DIY work, the use of unpaid help, and the use of contractors. It considers the types of work carried out, the characteristics of those who tackle DIY or use unpaid help, the dwelling types most likely to experience DIY work, and the motivations of and constraints on those home-owners who do it. The paper concludes with a discussion on the policy implications of these findings for government and the building industry. Although most DIY work is cosmetic and does not deal with basic repair and maintenance, the sheer scale of DIY ensures that it makes a contribution to improving housing conditions. The provision of more advice, information and education by government, local authorities and the private sector could ensure that more DIY work is of better quality and that home owners give priority to essential repairs whether or not they tackle these themselves.Building Do-IT-YOURSELF Housing Maintenance Repair,