A phase I study of the oral platinum agent satraplatin in sequential combination with capecitabine in the treatment of patients with advanced solid malignancies.

Abstract Background. The broad spectrum of antitumor activity of both the oral platinum analogue satraplatin (S) and capecitabine (C), along with the advantage of their oral administration, prompted a clinical study aimed to define the maximum tolerated dose (MTD) of the combination. Patients and methods. Four dose levels of S (mg/m(2)/day) and C (mg/m(2)/day) were evaluated in adult patients with advanced solid tumors: 60/1650, 80/1650, 60/2000, 70/2000; a course consisted of 28 days with sequential administration of S (days 1-5) and C (days 8-21) followed by one week rest. Results. Thirty-seven patients were treated, 24 in the dose escalation and 13 in the expansion phase; at the MTD, defined at S 70/C 2000, two patients presented dose limiting toxicities: lack of recovery of neutropenia by day 42 and nausea with dose skip of C. Most frequent toxicities were nausea (57%), diarrhea (51%), neutropenia (46%), anorexia, fatigue, vomiting (38% each). Two partial responses were observed in platinum sensitive ovarian cancer and one in prostate cancer. Conclusion. At S 70/C 2000 the combination of sequential S and C is tolerated with manageable toxicities; its evaluation in platinum and fluorouracil sensitive tumor types is worthwhile because of the easier administration and lack of nephro- and neurotoxicity as compared to parent compounds.

Effect of Platinum-Based Chemoradiotherapy on Cellular Proliferation in Bone Marrow and Spleen, Estimated by 18F-FLT PET/CT in Patients with Locally Advanced Non-Small Cell Lung Cancer.

Historically, it has been difficult to monitor the acute impact of anticancer therapies on hematopoietic organs on a whole-body scale. Deeper understanding of the effect of treatments on bone marrow would be of great potential value in the rational design of intensive treatment regimens. 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a functional radiotracer used to study cellular proliferation. It is trapped in cells in proportion to thymidine-kinase 1 enzyme expression, which is upregulated during DNA synthesis. This study investigates the potential of (18)F-FLT to monitor acute effects of chemotherapy on cellular proliferation and its recovery in bone marrow, spleen, and liver during treatment with 2 different chemotherapy regimens.

Survival of zirconia- and metal-supported fixed dental prostheses: a systematic review

Purpose: The aim of this review was to systematically evaluate and compare the frequency of veneer chipping and core fracture of zirconia fixed dental prostheses (FOPS) and porcelain-fused-to-metal (PFM) FDPs and determine possible influencing factors. Materials and Methods: The SCOPUS database and International Association of Dental Research abstracts were searched for clinical studies involving zirconia and PFM FDPs. Furthermore, studies that were integrated into systematic reviews on PFM FDPs were also evaluated. The principle investigators of any clinical studies on zirconia FDPs were contacted to provide additional information. Based on the available information for each FOP, a data file was constructed. Veneer chipping was divided into three grades (grade 1 = polishing, grade 2 = repair, grade 3 = replacement). To assess the frequency of veneer chipping and possible influencing factors, a piecewise exponential model was used to adjust for a study effect. Results: None of the studies on PFM FDPs (reviews and additional searching) sufficiently satisfied the criteria of this review to be included. Thirteen clinical studies on zirconia FDPs and two studies that investigated both zirconia and PFM FDPs were identified. These studies involved 664 zirconia and 134 PFM FDPs at baseline. Follow-up data were available for 595 zirconia and 127 PFM FDPs. The mean observation period was approximately 3 years for both groups. The frequency of core fracture was less than 1% in the zirconia group and 0% in the PFM group. When all studies were included, 142 veneer chippings were recorded for zirconia FDPs (24%) and 43 for PFM FDPs (34%). However, the studies differed extensively with regard to veneer chipping of zirconia: 85% of all chippings occurred in 4 studies, and 43% of all chippings included zirconia FDPs. If only studies that evaluated both types of core materials were included, the frequency of chipping was 54% for the zirconia-supported FDPs and 34% for PFM FDPs. When adjusting the survival rate for the study effect, the difference between zirconia and PFM FDPs was statistically significant for all grades of chippings (P = .001), as well as for chipping grade 3 (P = .02). If all grades of veneer chippings were taken into account, the survival of PFM FDPs was 97%, while the survival rate of the zirconia FDPs was 90% after 3 years for a typical study. For both PFM and zirconia FDPs, the frequency of grades 1 and 2 veneer chippings was considerably higher than grade 3. Veneer chipping was significantly less frequent in pressed materials than in hand-layered materials, both for zirconia and PFM FDPs (P = .04). Conclusions: Since the frequency of veneer chipping was significantly higher in the zirconia FDPs than PFM FDPs, and as refined processing procedures have started to yield better results in the laboratory, new clinical studies with these new procedures must confirm whether the frequency of veneer chipping can be reduced to the level of PFM. Int J Prosthodont 2010;23:493-502

Spleen Volume Variation in Patients with Locally Advanced Non-Small Cell Lung Cancer Receiving Platinum-Based Chemo-Radiotherapy.

There is renewed interest in the immune regulatory role of the spleen in oncology. To date, very few studies have examined macroscopic variations of splenic volume in the setting of cancer, prior to or during therapy, especially in humans. Changes in splenic volume may be associated with changes in splenic function. The purpose of this study was to investigate variations in spleen volume in NSCLC patients during chemo-radiotherapy. Sixty patients with stage I-IIIB NSCLC underwent radiotherapy (60Gy/30 fractions) for six weeks with concomitant carboplatin/paclitaxel (Ca/P; n = 32) or cisplatin/etoposide (Ci/E; n = 28). A baseline PET/CT scan was performed within 2 weeks prior to treatment and during Weeks 2 and 4 of chemo-radiotherapy. Spleen volume was measured by contouring all CT slices. Significant macroscopic changes in splenic volume occurred early after the commencement of treatment. A significant decrease in spleen volume was observed for 66% of Ca/P and 79% of Ci/E patients between baseline and Week 2. Spleen volume was decreased by 14.2% for Ca/P (p<0.001) and 19.3% for Ci/E (p<0.001) patients. By Week 4, spleen volume was still significantly decreased for Ca/P patients compared to baseline, while for Ci/E patients, spleen volume returned to above baseline levels. This is the first report demonstrating macroscopic changes in the spleen in NSCLC patients undergoing radical chemo-radiotherapy that can be visualized by non-invasive imaging.