Denosumab was noninferior (trending to superiority) to ZA in preventing or delaying first on-study SRE in patients with advanced cancer metastatic to bone or myeloma. Denosumab represents a potential novel treatment option with the convenience of subcutaneous administration and no requirement for renal monitoring or dose adjustment.

Patients with bacterial overgrowth of the small intestine developed spontaneous bacterial peritonitis (SBP) more frequently than patients without bacterial overgrowth of the small intestine. The objective of this study was to determine whether the incidences of small intestine dysmotility and bacterial overgrowth are higher in cirrhotic patients with a history of SBP than in cirrhotic patients without SBP. Forty cirrhotic patients were enrolled in this study. There were 20 patients with a history of SBP and 20 patients without a history of SBP. Small intestine bacterial overgrowth was diagnosed by breath hydrogen test. Small intestine motility was recorded, by a 3-channel solid-state manometric catheter, for 24 hours. There were no statistical differences in age or sex between the two groups. The Child-Pugh scores in the SBP group were higher than in the non-SBP group (10.5 ؎ 2.1 vs. 8.1 ؎ 1.9, P F .01). The incidence of bacterial overgrowth of the small intestine was higher in the SBP group than in the non-SBP group (70% vs. 20%, P F .01). The amplitude and duration of migrating motor complex (MMC) activity fronts, as well as the number of clusters per hour, were similar in both groups. However, the frequency of MMC activity fronts was higher in the non-SBP group than in the SBP group (4.8 ؎ 2.3/24 hours vs. 3.5 ؎ 1.2/24 hours, P F .05). In addition, the MMC velocity was significantly higher in the non-SBP group (8.3 ؎ 2.6 vs. 5.3 ؎ 2.1 cm/min, P F .01). The incidence of bacterial overgrowth of the small intestine was higher in cirrhotic patients with history of SBP than in those without SBP. Small intestine motility dysfunction was more severe in cirrhotic patients with history of SBP. Impaired motility of the small intestine, causing bacterial overgrowth of the small intestine, may be one of the explanations for recurrent SBP in cirrhotic patients. (HEPA-TOLOGY 1998;28:1187-1190.)Spontaneous bacterial peritonitis (SBP) is a serious problem in cirrhotic patients with ascites. The incidence of SBP is 10% to 25% among cirrhotic patients admitted to a hospital 1 ; SBP accounts for 30% of all infections in cirrhotic patients. 2,3 The overall mortality rate of a given episode of SBP is 30% to 50%. [4][5][6] Tito et al. reported a 69% recurrence rate of SBP at 1 year, 7 particularly in those patients with protein concentration in the ascites fluid of less than 1 gm/dL. 8 Most organisms cultured from ascites in patients with SBP are part of the normal aerobic flora of the gut. 1 As selective intestinal decontamination with antibiotics prevents recurrent SBP 9-11 as well as peritonitis which occurs after an acute gastrointestinal hemorrhage, 12 the port of entry appears to be the gut. In a prospective study on alcoholic liver cirrhosis, patients with bacterial overgrowth of the small intestine developed SBP more frequently than did those without bacterial overgrowth of the small intestine. 13 The association of abnormal jejunal interdigestive motility and bacterial overgrowth has been reported by Chesta et al. 14 The ...

Purpose Bone complications of metastatic disease, including skeletal-related events (SREs), impair patients' functioning and quality of life. In a randomized, phase 3 trial of 1,776 patients with metastases from solid tumors (except breast or prostate) or multiple myeloma, denosumab was non-inferior to zoledronic acid (ZA) in delaying or preventing SREs. This ad hoc analysis reports outcomes in the subgroup of 1,597 patients with solid tumors, excluding patients with multiple myeloma. Methods Patients received monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg, adjusted for creatinine clearance, with calcium and vitamin D supplementation recommended. Endpoints included times to first on-study SRE, first-and-subsequent SREs, and pain worsening. Results Denosumab significantly delayed time to first onstudy SRE compared with ZA (HR, 0.81; 95 % CI, 0.68-0.96) and time to first-and-subsequent SREs (RR, 0.85; 95 % CI, 0.72-1.00). Denosumab also significantly delayed time to development of moderate or severe pain (HR, 0.81; 95 % CI, 0.66-1.00), pain worsening (HR, 0.83; 95 % CI, 0.71-0.97), and worsening pain interference in patients with no/mild baseline pain (HR, 0.77; 95 % CI, 0.61-0.96). Adverse event rates were 96 % in both groups. Grade 3 or 4 hypocalcemia, mostly without clinical sequelae, was more frequent in denosumab-treated patients (denosumab 4 %, ZA 2 %). Osteonecrosis of the jaw occurred infrequently (denosumab 0.8 %, ZA 1.1 %). Conclusions Denosumab was more effective in delaying or preventing SREs in patients with bone metastases from solid tumors and also prevented pain progression compared to ZA in this ad hoc analysis.

To determine the efficacy and tolerability of an enteric-coated peppermint-oil formulation (Colpermin), we conducted a prospective, randomized, double-blind, placebo-controlled clinical study in 110 outpatients (66 men/44 women; 18-70 years of age) with symptoms of irritable bowel syndrome. Patients took one capsule (Colpermin or placebo) three to four times daily, 15-30 min before meals, for 1 month. Fifty-two patients on Colpermin and 49 on placebo completed the study. Forty-one patients on Colpermin (79%) experienced an alleviation of the severity of abdominal pain (29 were pain-free); 43 (83%) had less abdominal distension, 43 (83%) had reduced stool frequency, 38 (73%) had fewer borborygmi, and 41 (79%) less flatulence. Corresponding figures for the placebo group were: 21 patients (43%) with reduced pain (4 were pain-free), 14 (29%) with reduced distension, 16 (32%) with reduced stool frequency, 15 (31%) with fewer borborygmi, and 11 (22%) with less flatulence. Symptom improvements after Colpermin were significantly better than after placebo (P < 0.05; Mann-Whitney U-test). One patient on Colpermin experienced heartburn (because of chewing the capsules) and one developed a mild transient skin rash. There were no significant changes in liver function test results. Thus, in this trial, Colpermin was effective and well tolerated.

Key Points• Daratumumab plus lenalidomide/dexamethasone elicited an overall response rate of 81% (63% very good partial response or better).• Adverse events were manageable and in accord with the individual toxicity profiles of daratumumab and lenalidomide/ dexamethasone.Daratumumab, a human CD38 immunoglobulin G1 kappa (IgG1k) monoclonal antibody, has activity as monotherapy in multiple myeloma (MM). This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM. Part 1 (dose escalation) evaluated 4 daratumumab doses plus lenalidomide (25 mg/day orally on days 1-21 of each cycle) and dexamethasone (40 mg/week). Part 2 (dose expansion) evaluated daratumumab at the recommended phase 2 dose (RP2D) plus lenalidomide/dexamethasone. Safety, efficacy, pharmacokinetics, immunogenicity, and accelerated daratumumab infusions were studied. In part 1 (13 patients), no dose-limiting toxicities were observed, and 16 mg/kg was selected as the R2PD. In part 2 (32 patients), median time since diagnosis was 3.2 years, with a median of 2 prior therapies (range, 1-3 prior therapies), including proteasome inhibitors (91%), alkylating agents (91%), autologous stem cell transplantation (78%), thalidomide (44%), and lenalidomide (34%); 22% of patients were refractory to the last line of therapy. Grade 3 to 4 adverse events ( ‡5%) included neutropenia, thrombocytopenia, and anemia. In part 2, infusion-related reactions (IRRs) occurred in 18 patients (56%); most were grade £2 (grade 3, 6.3%). IRRs predominantly occurred during first infusions and were more common during accelerated infusions. In part 2 (median follow-up of 15.6 months), overall response rate was 81%, with 8 stringent complete responses (25%), 3 complete responses (9%), and 9 very good partial responses (28%). Eighteen-month progression-free and overall survival rates were 72% (95% confidence interval, 51.7-85.0) and 90% (95% confidence interval, 73.1-96.8), respectively. Daratumumab plus lenalidomide/dexamethasone resulted in rapid, deep, durable responses. The combination was well tolerated and consistent with the safety profiles observed with lenalidomide/ dexamethasone or daratumumab monotherapy. This trial was registered at www.clinicaltrials.gov as