A dose escalation study of docetaxel plus capecitabine in combination with oxaliplatin in patients with advanced solid tumors.

OBJECTIVES: Capecitabine (CAP), Oxaliplatin (OX) and Docetaxel (DOC) have shown considerable activity in a wide range of solid tumors. A phase I study was conducted in order to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of their combination in patients with advanced solid tumors. PATIENTS AND METHODS: Twenty-one patients were enrolled. The patient's median age was 68 years, 15 were male, and 12 were chemo-naïve. DOC was administered on day 1 as an 1-hour (iv) infusion at a standard dose of 50 mg/m(2). OX was administered on day 1 as a 2-hour (iv) infusion at escalating doses ranging from 70-80 mg/m(2). CAP was administered orally on days 1 to 7 at escalating doses ranging from 2,000-2,750 mg/m(2) given as two daily divided doses. Treatment was repeated every two weeks. RESULTS: Six different dose-levels were examined. At dose-level VI, two of three enrolled patients presented DLTs (one patient diarrhea and asthenia grade 3 and another grade 3 diarrhea), and thus, the recommended MTD for future phase II studies is CAP 2,750 mg/m(2) , DOC 50 mg/m(2) and OX 75 mg/m(2). A total of 121 treatment cycles were administered. Grade 3 neutropenia was observed in six (5%) treatment cycles and grade 3 thrombocytopenia in one (1%). There was no febrile episode. Grade 3 asthenia was observed in three (14%) patients, grade 3 diarrhea in four (19%), grade 3 neuropathy in one (5%), and grade 1/2 hand-foot syndrome in three (14%). Other toxicities were uncommon. There was no treatment related death. Four (29%) PRs and seven (50%) SD were observed among 14 evaluable patients. Responses were seen in patients with renal (n = 1), gastric (n = 2) and pancreatic (n = 1) cancer. CONCLUSIONS: These results demonstrate that CAP, DOC and OX can be safely combined at clinically relevant doses and this regimen merits further evaluation.

U-stitching splenorraphy technique: experimental and clinical study.

BACKGROUND: The aim of the present study was to describe the laboratory development and the subsequent clinical utility of the U-stitching technique for splenorraphy over the recent years in a general non-trauma hospital. Patients with splenectomies and patients treated conservatively during the same time period, are also presented. METHODS: In the 15-year period from September 1988 until September 2003, 65 patients were diagnosed with splenic injury following admission to 2nd Department of Surgery, Democritus University Hospital, after blunt abdominal trauma. During the first 3 years, 14 patients were admitted; one of them was treated conservatively and 13 had splenectomies. Because computed tomography (CT) was not available at that time, these 14 patients form a control group. During the remaining 12-year period, 51 patients (39 male and 12 female; age, 4-82 years; mean, 31.1 years; SD, 19.7 years) were treated conservatively or surgically, either with splenectomy or with splenorraphy. Splenorraphy was performed using the U-stitching technique. This alternative splenorraphy technique was first tested on experimental models at 2nd Department of Surgery, Democritus University Hospital, then followed by successful clinical application. The medical records for these patients were reviewed to extract the data for the present study. RESULTS: Thirty-six patients (70.6% of 51 patients) were treated surgically; of these, 21 (41.2% of 51 patients) had splenectomy and 15 (29.4% of 51 patients) had splenorraphy. Non-operative treatment was initially given to 15 patients (29.4% of 51 patients). Two of them had delayed rupture of the spleen and underwent splenectomy (at 8 and 40 days). The total number of preserved spleens was 28 of 51 (54.9%). None of the patients with conservative treatment or splenorraphy died. One patient with splenectomy died later from overwhelming sepsis. CONCLUSIONS: Splenic salvage is now a treatment goal. If the patient is haemodynamically unstable and splenorraphy is possible, the U-stitching technique is a promising approach.