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VTE remains a common complication of cancer surgery, with a remarkable proportion of events occurring late after surgery. In patients undergoing cancer surgery, VTE is the most common cause of death at 30 days after surgery.

BackgroundCancer patients receiving chemotherapy are at increased risk of thrombosis. Nadroparin has been demonstrated to reduce the incidence of venous and arterial thrombotic events (TEs) by about 50% in cancer outpatients receiving chemotherapy. The aims of this retrospective analysis were to evaluate the thromboembolic risk and the benefit of thromboprophylaxis according to type of chemotherapy.MethodsCancer outpatients were randomly assigned to receive subcutaneous injections of nadroparin or placebo. The incidence of symptomatic TEs was assessed according to the type of chemotherapy. Results were reported as risk ratios with associated 95% CI and two-tailed probability values.Results769 and 381 patients have been evaluated in the nadroparin and placebo group, respectively. In the absence of thromboprophylaxis, the highest rate of TEs was found in patients receiving gemcitabine- (8.1%) or cisplatin-based chemotherapy (7.0%). The combination of gemcitabine and cisplatin or carboplatin increased the risk to 10.2%. Thromboprophylaxis reduced TE risk by 68% in patients receiving gemcitabine; with a further decrease to 78% in those receiving a combination of gemcitabine and platinum.ConclusionsThis retrospective analysis confirms that patients undergoing chemotherapy including gemcitabine, platinum analogues or their combination are at higher risk of TEs. Our results also suggest that outpatients receiving chemotherapy regimens including these agents might achieve an increased benefit from thromboprophylaxis with nadroparin. Clinical Trial registration number: NCT 00951574

Background Standardized salvage treatment has not yet proved eVective in glioblastoma multiforme (GBM) patients who receive prior standard radiotherapy plus concomitant and adjuvant temozolomide. Methods Patients with progressive GBM after radiotherapy plus concomitant and/or adjuvant temozolomide received three-weekly doses (100-75 mg m 2 ) of fotemustine followed, after a 5-week rest, by fotemustine (100 mg m 2 ) every 3 weeks for ·1 year. Results Forty-three patients (29 M, 14 F; median age 51 years, range 34-68; median KPS 90) were enrolled. Progression-free survival at 6 months (PFS-6) was 20.9% (95% CI: 9-33%); three patients (7.1%) had partial response (PR); 15 (34.9%), disease stabilization (SD). The median survival was 6 months (95% CI: 5-7). MGMT promoter status was methylated in 8 (18.6%) and unmethylated in 26 (60.5%) and not assessable in 9 (20.9%) patients, respectively. Disease control was 75% versus 34.6% in methylated and unmethylated MGMT patients (P = 0.044); no signiWcant diVerence was found between groups for PFS-6 and survival. Grade 3 and 4 thrombocytopenia and neutropenia were observed in 20.9 and 16.3% of patients, during the induction phase, and in 0 and 9.5% patients during the maintenance phase, respectively. Conclusions The Wndings of the present trial, that evaluate fotemustine in a homogeneous population, may represent a new benchmark for nitrosourea activity. Moreover, this is the Wrst study to evaluate correlation between MGMT promoter status and outcome of fotemustine for relapsing GBM previously treated with radiotherapy and temozolomide.

The present results appear to be encouraging in terms of complete prophylaxis of CINV and treatment of breakthrough emesis in the setting of multiple-day chemotherapy.

The aim of this study was to determine the efficacy of palonosetron combined with dexamethasone in prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) in patients receiving high-dose (HD)-CT with auto-SCT, and the efficacy of a second dose of palonosetron in treating breakthrough emesis. One hundred thirty-four patients treated with HD-CT and auto-SCT for hematologic malignancies received palonosetron as prophylaxis for CINV on the first day of conditioning; patients were also administered dexamethasone throughout the entire period of conditioning. If breakthrough emesis occurred, a second dose of palonosetron was administered at 72 h after the first administration. Complete response and complete protection were observed in 36 and 26% of patients, respectively. One-half of the patients, re-treated with palonosetron for breakthrough emesis, were successfully rescued. Treatment with palonosetron plus dexamethasone seems to be encouraging in terms of prophylaxis of CINV and treatment of breakthrough emesis in the setting of HD-CT.

Calcium supplementation is widely used in deficiency status and as an adjuvant in the treatment of osteoporosis. As usual with endogenous substances, the calcium absorption, distribution and elimination processes are strictly controlled by homeostatic equilibria. Free calcium ion is the most representative active fraction of the circulating ion. Ion excretion is controlled by a saturable tubular reabsorption process which leads to a renal threshold. Cumulative urinary excretion of calcium is the end-point of absorption, distribution and elimination processes, and is thus a good indicator of bioavailability. In order to increase the oral bioavailability of calcium, the ion is administered in association with vitamin D, which is known to enhance intestinal calcium absorption. The aim of this study was to evaluate the absorption of calcium administered alone and in fixed combination with cholecalciferol (vitamin D3, CAS 67-97-0). In accordance with the study protocol, calcium carbonate (CAS 471-34-1; 1500 mg = 600 mg as calcium ion) was administered as such (reference) and associated with cholecalciferol (400 IU) (test) for four days (2 doses/day) to 18 healthy male volunteers in a sequential pattern, namely reference followed by test. Urinary excretion of total calcium, and serum concentration of free and total calcium, 25-OH-vitamin D3 and parathyroid hormone were carefully analysed the day before (baseline) and on the 4th day of dosing, with validated methods. The effect of cholecalciferol in promoting calcium absorption was clearly observed from urinary excretion of total calcium, which with the test treatment showed a 16.6% increase in excretion (p = 0.025) compared with the reference treatment. The mean excretion values on the 4th day, expressed in mg, were 238.85 and 204.83 with test and reference respectively. Moreover, the results demonstrated an increased serum concentration of both free and total calcium after dosing with test and reference by comparison with the baseline situation. The area under the serum concentration-time curve of total calcium increased from day -1 to day 4 from 550.98 to 575.90 mg l-1 h with test and from 543.03 to 568.16 mg l-1 h with reference. Similarly, ionised calcium increased on day 4 with both the treatments. Parathyroid hormone showed the expected typical decreasing behaviour after dosing with the test and reference drugs. The results of this study suggest that calcium carbonate is absorbed through the intestine when administered either alone or in association with cholecalciferol. Cholecalciferol, however, showed the typical expected activity in promoting calcium absorption, which was evident from the cumulative urinary excretion of the ion. To the authors' knowledge, this study is the first published paper demonstrating the absorption and pharmacodynamic effect of short-term administration of vitamin D associated with calcium at the doses recommended for supplementation in a fixed-combination pharmaceutical product.