Combined chemoradiotherapy with gemcitabine in patients with locally advanced inoperable transitional cell carcinoma of the urinary bladder and/or in patients ineligible for surgery: a phase I trial.

BACKGROUND: We conducted a phase I trial of gemcitabine (gem) with concurrent radiotherapy in patients with muscle-invasive bladder cancer (BC) ineligible for surgery or cisplatin or refusing organ loss. PATIENTS AND METHODS: Patients with urothelial cancer, cT2-T4, cN0-1, M0, ineligible for surgery due to local tumor extension, PS, age or co-morbidities or who refused surgery were included. After maximal transurethral resection, the treatment schedule included: twice-weekly i.v. infusion of gem [dose levels (DL) 1-6: 20, 27, 30, 33, 50 and 40 mg/m(2), respectively] for 30 min and concurrent radiotherapy (RT) to the bladder with 55.5 Gy. The primary end point was to determine the maximum-tolerated dose (MTD) and the dose recommended (RD) for further studies of this gem schedule. The secondary end point was late toxicity. The MTD was defined by dose-limiting toxicity (DLT) in 2 or more of 6 patients, discontinuation of RT and/or gem for >1 week in 2 or more of 6 patients due to grade (G) 3/4 acute and/or late toxicity in more than 2 of 18 patients. RESULTS: Thirty-five of 44 patients were assessable for toxicity and thus the primary end point. DLTs occurred in two of five patients at dose level 5: one G3 alanine aminotransferase elevation and one G3 fatigue. The MTD, therefore, was 50 mg/m(2) gem twice weekly. At DL 6 with 40 mg/m(2), the RD was established: only one of six patients developed G3 fatigue and diarrhea. Late toxicity was rare and of low grade (only G1-2). The 2-year locoregional failure rate was 32% (9/28); 10 of 28 patients (38%) were alive with an intact bladder and no evidence of recurrent disease, 9 patients developed distant metastases and 6 died of their disease. CONCLUSIONS: Gemcitabine in combination with RT is well tolerated in BC patients ineligible for surgery and/or cisplatin. The RD of gemcitabine for subsequent trials is 40 mg/m(2) twice weekly with concurrent radiation.

The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2- breast cancer patients.

BACKGROUND: ER+/HER2- breast cancers have a proclivity for late recurrence. A personalised estimate of relapse risk after 5 years of endocrine treatment can improve patient selection for extended hormonal therapy. METHODS: A total of 1702 postmenopausal ER+/HER2- breast cancer patients from two adjuvant phase III trials (ABCSG6, ABCSG8) treated with 5 years of endocrine therapy participated in this study. The multigene test EndoPredict (EP) and the EPclin score (which combines EP with tumour size and nodal status) were predefined in independent training cohorts. All patients were retrospectively assigned to risk categories based on gene expression and on clinical parameters. The primary end point was distant metastasis (DM). Kaplan-Meier method and Cox regression analysis were used in an early (0-5 years) and late time interval (>5 years post diagnosis). RESULTS: EP is a significant, independent, prognostic parameter in the early and late time interval. The expression levels of proliferative and ER signalling genes contribute differentially to the underlying biology of early and late DM. The EPclin stratified 64% of patients at risk after 5 years into a low-risk subgroup with an absolute 1.8% of late DM at 10 years of follow-up. CONCLUSION: The EP test provides additional prognostic information for the identification of early and late DM beyond what can be achieved by combining the commonly used clinical parameters. The EPclin reliably identified a subgroup of patients who have an excellent long-term prognosis after 5 years of endocrine therapy. The side effects of extended therapy should be weighed against this projected outcome.

EndoPredict improves the prognostic classification derived from common clinical guidelines in ER-positive, HER2-negative early breast cancer.

BACKGROUND: In early estrogen receptor (ER)-positive/HER2-negative breast cancer, the decision to administer chemotherapy is largely based on prognostic criteria. The combined molecular/clinical EndoPredict test (EPclin) has been validated to accurately assess prognosis in this population. In this study, the clinical relevance of EPclin in relation to well-established clinical guidelines is assessed. PATIENTS AND METHODS: We assigned risk groups to 1702 ER-positive/HER2-negative postmenopausal women from two large phase III trials treated only with endocrine therapy. Prognosis was assigned according to National Comprehensive Cancer Center Network-, German S3-, St Gallen guidelines and the EPclin. Prognostic groups were compared using the Kaplan-Meier survival analysis. RESULTS: After 10 years, absolute risk reductions (ARR) between the high- and low-risk groups ranged from 6.9% to 11.2% if assigned according to guidelines. It was at 18.7% for EPclin. EPclin reassigned 58%-61% of women classified as high-/intermediate-risk (according to clinical guidelines) to low risk. Women reclassified to low risk showed a 5% rate of distant metastasis at 10 years. CONCLUSION: The EPclin score is able to predict favorable prognosis in a majority of patients that clinical guidelines would assign to intermediate or high risk. EPclin may reduce the indications for chemotherapy in ER-positive postmenopausal women with a limited number of clinical risk factors.

2-¹8fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) for postchemotherapy seminoma residual lesions: a retrospective validation of the SEMPET trial.

BACKGROUND: 2-¹8fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) has been recommended in international guidelines in the evaluation of postchemotherapy seminoma residuals. Our trial was designed to validate these recommendations in a larger group of patients. PATIENTS AND METHODS: FDG-PET studies in patients with metastatic seminoma and residual masses after platinum-containing chemotherapy were correlated with either the histology of the resected lesion(s) or the clinical outcome. RESULTS: One hundred and seventy seven FDG-PET results were contributed. Of 127 eligible PET studies, 69% were true negative, 11% true positive, 6% false negative, and 15% false positive. We compared PET scans carried out before and after a cut-off level of 6 weeks after the end of the last chemotherapy cycle. PET sensitivity, specificity, negative predictive value (NPV), and positive predictive value were 50%, 77%, 91%, and 25%, respectively, before the cut-off and 82%, 90%, 95%, and 69% after the cut-off. PET accuracy significantly improved from 73% before to 88% after the cut-off (P=0.032). CONCLUSION: Our study confirms the high specificity, sensitivity, and NPV of FDG-PET for evaluating postchemotherapy seminoma residuals. When carried out at an adequate time point, FDG-PET remains a valuable tool for clinical decision-making in this clinical setting and spares patients unnecessary therapy.

[Role of chemotherapy in castration-resistant prostate cancer: are there new approaches?]. / Rolle der Chemotherapie beim kastrationsresistenten Prostatakarzinom : Gibt es neue Ansätze?

Chemotherapy options for the treatment of metastatic castration-resistant prostate cancer (CRPC) have been very limited for many decades. Until 2004, only mitoxantrone was approved, providing palliation, but no survival benefit. With the introduction of docetaxel, the landscape of chemotherapy for CRPC changed substantially. Prednisone and three-weekly docetaxel showed an overall survival (OS) benefit compared to mitoxantrone plus prednisone, in addition to a significant improvement of quality of life and pain reduction. Further strategies to treat CRPC with chemotherapy include reinduction with docetaxel in responding patients and the use of cabazitaxel, a novel semi-synthetic microtubule inhibitor, in the docetaxel-refractory population. This review article is meant to guide physicians through the optimal use of chemotherapy in CRPC patients in daily clinical practice.

A follow-up of psychological state in relatives of cancer patients one year after the patient's death. Effects of an activation programme.

A follow-up of psychological state in relatives of cancer patients twelve months after the patient's death was carried out in a controlled study. Relatives who were offered an activation programme (activation group) were compared with relatives not offered this programme (comparison group). A translation of Holland and Sgroi's standardized rating schedule for psychologic states and an interview based upon Bowlby's attachment theory were used to assess psychological outcome. Relatives in the activation group reported better mental state and less depression than those in the comparison group. Relatives in the activation group also reported fewer problems with health and anger than those in the comparison group. Furthermore, relatives in the activation group showed a more positive attitude to the care than those in the comparison group. All the differences mentioned were statistically significant.