http://repub.eur.nl/res/aut/30691/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/35011/ 2012-01-10T00:00:00Z Purpose: This is the first randomized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ("unfit") for cisplatin chemotherapy. Patients and Methods: The primary objective of the phase III part of this study was to compare the overall survival (OS) of chemotherapy-naive patients with measurable disease and an impaired renal function (glomerular filtration rate < 60 but > 30 mL/min) and/or performance score of 2 who were randomly assigned to receive either gemcitabine/carboplatin (GC) or methotrexate/carboplatin/ vinblastine (M-CAVI). To detect an increase of 50% in median survival with GC compared with M-CAVI (13.5 v 9 months) based on a two-sided log-rank test at error rates α .05 and β =.20, 225 patients were required. Secondary end points were overall response rate (ORR), progression-free survival (PFS), toxicity, and quality of life. Results: In all, 238 patients were randomly assigned by 29 institutions over a period of 7 years. The median follow-up was 4.5 years. Best ORRs were 41.2% (36.1% confirmed response) for patients receiving GC versus 30.3% (21.0% confirmed response) for patients receiving M-CAVI (P=.08). Median OS was 9.3 months in the GC arm and 8.1 months in the M-CAVI arm (P=.64). There was no difference in PFS (P=.78) between the two arms. Severe acute toxicity (death, grade 4 thrombocytopenia with bleeding, grade 3 or 4 renal toxicity, neutropenic fever, or mucositis) was observed in 9.3% of patients receiving GC and 21.2% of patients receiving M-CAVI. Conclusion There were no significant differences in efficacy between the two treatment groups. The incidence of severe acute toxicities was higher for those receiving M-CAVI. http://repub.eur.nl/res/pub/24397/ 2009-12-01T00:00:00Z Purpose: To evaluate the roles of radiation dose, chemotherapy, and other factors in the etiology of stomach cancer in long-term survivors of testicular cancer or Hodgkin lymphoma. Methods and Materials: We conducted a cohort study in 5,142 survivors of testicular cancer or Hodgkin lymphoma treated in the Netherlands between 1965 and 1995. In a nested case-control study, detailed information on treatment, smoking, gastrointestinal diseases, and family history was collected for 42 patients with stomach cancer and 126 matched controls. For each subject, the mean radiation dose to the stomach was estimated. Relative risks (RRs) of stomach cancer and the radiation-related excess relative risk (ERR) per gray were calculated by conditional logistic regression analysis. Results: The risk of stomach cancer was 3.4-fold increased compared with the general population. The risk increased with increasing mean stomach dose (p for trend, <0.001), at an ERR of 0.84 per Gy (95% confidence interval [CI], 0.12-15.6). Mean stomach doses of more than 20 Gy were associated with a RR of 9.9 (95% CI, 3.2-31.2) compared with doses below 11 Gy. The risk was 1.8-fold (95% CI, 0.8-4.4) increased after chemotherapy and 5.4-fold (95% CI, 1.2-23.9) increased after high doses of procarbazine (≥13,000 mg) vs. <10,000 mg. The RR of smoking more than 10 cigarettes per day vs. no smoking was 1.6 (95% CI, 0.6-4.2). Conclusions: Stomach cancer risk is strongly radiation dose dependent. The role of chemotherapy, particularly of procarbazine and related agents, needs further study, because of the relatively small numbers of chemotherapy-treated subjects.