Lucio Patoia

Predictive factors of delayed emesis in cisplatin-treated patients and antiemetic activity and tolerability of metoclopramide or dexamethasone : a randomized single-blind study

To prevent delayed emesis induced by cisplatin (mean dose 90 mg/m2), 120 consecutive patients were randomized to receive, in a 7-day crossover design, oral metoclopramide (20 mg q.i.d.), dexamethasone (1 mg q.i.d.) or placebo (two tablets q.i.d.) starting 24 hours after the end of chemotherapy. Complete protection from nausea, but not from vomiting. was significantly increased by both dexamethasone and metoclopramide with respect to placebo. Important prognostic factors favoring the appearance of delayed emesis were incomplete protection from vomiting during the first 24 hours after cisplatin, female gender, and highest cisplatin doses. Tolerability of both drugs was good. Larger and randomized controlled trials are necessary to identify better preventive treatment of delayed emesis induced by cisplatin.

Severe gastric mucosal damage induced by NSAIDs in healthy subjects is associated withHelicobacter pylori infection and high levels of serum pepsinogens

Helicobacter pylori infection and NSAIDs are considered the two most important exogenous factors in ulcer disease. The interrelation between the two factors is not, however, clear. Moreover, serum pepsinogen has been suggested as a risk marker for the development of NSAID-induced gastrointestinal lesions. Fifty-one healthy volunteers, enrolled in a prospective, double-blind study carried out to evaluate gastrointestinal side effects of meloxicam and piroxicam, were analyzed to determine whether: (1) the prevalence ofH. pylori correlates with the occurrence and severity of NSAID-induced gastrointestinal lesions, and (2) serum pepsinogen A and C levels could be used as markers of NSAID-induced mucosal damage. Upper endoscopy was performed by the same investigator before and after 28 days of treatment with placebo, meloxicam (7.5 mg/day and 15 mg/day), or piroxicam (20 mg/day). NSAID-induced damage was graded separately for hemorrhages and erosion ulcers according to Lanzas scale. There were no statistically significant differences in the prevalence ofH. pylori in subjects with and without NSAID-induced mucosal lesions. However, there was a positive association betweenH. pylori infection and the severity of mucosal damage: total mean endoscopic score was 2.9±0.3 inH. pylori-positive subjects versus 1.6±0.5 inH. pylori-negative subjects (P<0.05). Pepsinogen A and C levels increased from 55.3±3 to 149.4±15 and from 6.3±0.5 to 11.5±2.2, respectively (P<0.05) in subjects who developed severe endoscopic injury. It is concluded thatH. pylori increases the severity of NSAID-induced gastrotoxicity and that pepsinogen A and C levels are valid markers of severe NSAID-induced mucosal lesions.

Assessment of nausea

SummaryIn a standardized way three different methods of measuring nausea have been assessed in 849 patients enrolled in 4 double blind, randomized, clinical trials, and 2 observational studies. Nausea was measured before and 2, 4, 6, 8 and 24 hours after cancer chemotherapy by using a discrete scale (DS), a visual analogue scale (VAS) and a continuous chromatic analogue scale (ACCS), and it was evaluated according to 4 different dimensions: maximal intensity (MI) entity (E) duration (D) and quantity (Q).The distributions of nausea measurements in the population, agreement between the scales and their sensitivity, and agreement between dimensions and their sensitivity were analyzed.A uniform distribution of nausea measurements was found only in patients receiving chemotherapy without any antiemetic treatment. There was substantial equivalence of the different scales, and no advantage was shown an using an analogue (VAS) than a discrete (DS) scale.A trend toward increasing sensitivity in detecting differences as the dimensions of nausea considered became more inclusive of the various aspects of this symptom (Q more sensible than E more sensible than MI) was observed.

Pharmacokinetics and tolerability of teicoplanin in healthy volunteers after single increasing doses.

In this double-blind, randomized study, five healthy subjects per group received doses of 15, 20, or 25 mg of teicoplanin per kg of body weight, and one subject per group received a 0.9% NaCl placebo as single intravenous infusion over 30 min. Serial blood samples and urine were collected for 13 days postadministration, and concentrations of teicoplanin were determined by microbiological assay. The pharmacokinetic data were analyzed by noncompartmental and compartmental analyses. Laboratory safety tests, audiometry, and serum creatinine clearance measurements were done prior to day 1 and on days 2 and 14. In the three groups, peak levels at the end of the infusion averaged 194, 197, and 253 mg/liter, respectively. Mean concentrations in plasma 24 h after the administration were 10.5, 13.6, and 19.8 mg/liter, respectively. Mean values of volume of distribution at steady state were 0.80, 0.87, and 0.87 liters/kg, respectively. Terminal half-lives averaged 88, 83, and 92 h. Mean total clearance values were 10.9, 11.0, and 11.3 mg/h/kg, respectively, with renal clearance accounting for 75, 81, and 78%, respectively, of the total. The 13-day cumulative mean urinary recovery ranged from 71 to 78% of the dose within the groups. The pharmacokinetics of teicoplanin appears to be linear in the range of administered doses. Teicoplanin was generally well tolerated. Side effects, appearing in five subjects, were represented by fevers, chills, and skin reactions; these adverse reactions were mild, but one episode of rash necessitated the interruption of infusion, and one episode of chills necessitated treatment with corticosteroids. There was no indication of drug-related modifications of laboratory test results.

Effects of parenteral diclofenac sodium on upper gastrointestinal motility after food in man

SummaryIn experimental animal models nonsteroidal anti-inflammatory drugs may influence gastrointestinal motility, but as evidence is lacking in man. The effect of diclofenac sodum 75 mg i.m. on the motor response of the upper gastrointestinal tract to food has been studied by manometry in 9 healthy volunteers. Diclofenac had no effect on the motor activity of the stomach, duodenum, or jejunum after a 605 kcal meal.

Norfloxacin and Neutropenia

Excerpt To the editor: Norfloxacin is a fluoro-quinolone used to treat urinary tract infections (1). Although decreased leukocyte or neutrophil counts have been reported in about 1% of patients rec...

Ceftriaxone versus aztreonam plus cefazolin for infections in cancer patients with adequate neutrophil counts.

SummaryIn a prospective randomized trial, 154 febrile episodes in cancer patients with adequate neutrophil counts (>1,000 cells/mm3) were treated with either ceftriaxone (72 episodes) or aztreonam plus cefazolin (82 episodes). Documented infections represented almost half of the febrile episodes. The overall response rates among the 144 evaluable episodes were similar for the two regimens: 76% (51/67) with ceftriaxone versus 82% (63/77) with aztreonam plus cefazolin (p=0.41, not significant). Although not statistically significant, the response rate of the microbiologically documented infections was slightly better in patients treated with the double β-lactam combination (85% vs. 65%, p=0.16) and clinically documented infections showed a better response in the group of patients receiving monotherapy (87% vs. 59%, p=0.12). No serious adverse effects were observed during this study and both regimens were well tolerated. Ceftriaxone or the combination of aztreonam plus cefazolin showed a similar efficacy as empirical therapy for infections in cancer patients with adequate neutrophil counts.Zusammenfassung154 Fieberschübe bei Krebspatienten mit adäquaten Neutrophilenzahlen (>1.000 Zellen/mm3) wurden in einer prospektiven randomisierten Studie entweder mit Ceftriaxon (72 Episoden) oder Aztreonam plus Cefazolin (82 Episoden) behandelt. Nahezu die Hälfte der fieberhaften Episoden waren dokumentierte Infektionen. Die Gesamtansprechrate bei den 144 auswertbaren Episoden war für beide Therapien ähnlich: 76% für Ceftriaxon (51/67) und 82% für Aztreonam plus Cefazolin (63/77) (p=0,41; nicht signifikant). Bei mikrobiologisch dokumentierten Infektionen war die Ansprechrate unter der Doppel-Betalaktam-Kombination etwas besser (85 % im Vergleich zu 65%; p=0,16), doch war dieser Unterschied nicht signifikant. Bei den klinisch dokumentierten Infektionen zeigten die mit der Monotherapie behandelten Patienten bessere Ansprechraten (87% gegenüber 59%; p=0,12). Während der Studie wurden keine ernsthaften Nebenwirkungen beobachtet, beide Therapien wurden gut vertragen. In der empirischen Therapie von Infektionen bei Krebspatienten mit adäquaten Neutrophilenzahlen erwiesen sich Ceftriaxon und die Kombination von Aztreonam plus Cefazolin als vergleichbar wirksam.

The evaluation of acute gastrointestinal toxicity of NSAIDs in phase I clinical trials: a critical appraisal

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs and, excluding salicylates, are represented by more than 100 different compounds. Mucosal damage to the upper gastrointestinal (GI) tract is a side-effect common to all NSAIDs. Despite their obvious benefits, the damage they cause in the GI tract is a major health problem in current clinical practice [1]. Although a vast amount of information has accumulated on this topic over many years, only the data published in the very recent past provide convincing evidence that NSAIDs cause severe GI complication and allow the risk to be roughly quantified. Upper GI toxicity occuring after administration of NSAIDs can present a wide spectrum of clinical expressions ranging from relatively mild, but nonetheless discomforting, conditions such as epigastric pain and dyspepsia, to the more serious and potentially life-threatening states, namely GI ulceration and GI bleeding or perforation. Endoscopic evaluation of the upper GI tract in patients treated with NSAIDs reveals a number of lesions that range from simple erythema through diffuse erosions and/or microbleeding to ulceration [2–4]. Roth and Bennett [5] have recently proposed the term ‘NSAID gastropathy’ to describe those lesions associated with the upper GI tract toxicity that are encountered during NSAID therapy. Damage to the upper GI tract is not limited to the stomach, but can also involve the duodenum and, albeit infrequently, the oesophagus and the intestine.