Optimal combination therapy with Navoban (tropisetron) in patients with incomplete control of chemotherapy-induced nausea and vomiting. The Belgian Navoban Group.

Even with the availability of potent and selective serotonin antagonists, chemotherapy-induced nausea and vomiting remain a major problem for many patients. This study aims to evaluate the benefit of combination therapy based on Navoban (tropisetron) in patients who had incomplete control of nausea and/or vomiting induced by chemotherapy when using Navoban as a single antiemetic agent. In their first chemotherapy course, 1072 patients planned to receive at least two identical cycles of emetogenic chemotherapy were treated with 5 mg Navoban once daily. To evaluate three treatments additional to the recommended 5 mg once-daily Navoban regimen during Course 2 in those patients who had shown incomplete control of nausea and/or vomiting on any day of Course 1, a 2 x 2 x 2 factorial design was employed. Of these patients, 445 were centrally randomised to receive an additional dose of open-label dexamethasone (Day 1, 0.2 mg/kg i.v.; Days 2-6, 8 mg p.o.) and/or open-label alizapride (Day 1, 100 mg i.v. and 4 x 50 mg p.o.; Days 2-6, 4 x 5 mg p.o.) and/or double-blind Navoban--that is, doubling the dose to 10 mg once daily or placebo. Complete response rates during Course 1 (CRR, no nausea and no vomiting) were, for Day 1, 72% and for Days 1-6, 48%. More complete responders were observed when dexamethasone was added during Course 2, both on Day 1 (76% vs. 66%, p = 0.020) and on Days 1-6 (50% vs. 34%, p = 0.0004).(ABSTRACT TRUNCATED AT 250 WORDS)

Optimal combination therapy with tropisetron in 445 patients with incomplete control of chemotherapy-induced nausea and vomiting.

PURPOSE: This study evaluated tropisetron (Navoban; Sandoz Pharma, Basle, Switzerland)-based combination therapy in patients who had incomplete control of chemotherapy-induced nausea or vomiting when using tropisetron as a single antiemetic agent. PATIENTS AND METHODS: One thousand seventy-two patients, who were scheduled to receive at least two identical cycles of emetogenic chemotherapy, were treated with 5 mg tropisetron once daily in their first chemotherapy course. A 2 x 2 x 2 factorial design was used to evaluate three additional treatments to the recommended 5 mg once daily (intravenously [i.v.] on day 1; orally on days 2 through 6) tropisetron regimen during course 2 in those patients who had shown incomplete control of nausea and/or vomiting on any day of course 1. Four hundred forty-five patients were centrally randomized to receive, in addition, open-label dexamethasone (day 1, 0.2 mg/kg i.v.; days 2 through 6, 8 mg orally) and/or open-label alizapride (day 1, 100 mg i.v. and 4 x 50 mg orally; days 2 through 6, 4 x 50 mg orally) and/or double-blind tropisetron (ie, doubling the dose to 10 mg once daily) or corresponding placebo. RESULTS: Complete response rates (no nausea and no vomiting) were 72% for day 1 and 48% for days 1 through 6 of course 1. During course 2, more complete responders were observed when dexamethasone was added, both for day 1 (76% v 66%, P = .020) and for days 1 through 6 (50% v 34%, P = .0004). A moderate increase in the complete response rate was seen with the addition of conventional-dose alizapride (day 1, 75% v 68%, P = .14; days 1 through 6: 47% v 37%, P = .041). Doubling the dose of tropisetron did not change the complete response rate. CONCLUSION: The addition of dexamethasone significantly increases the complete response rate of both acute and delayed emesis in patients who have incomplete disease control with tropisetron alone.

At equipotent doses, isradipine is better tolerated than amlodipine in patients with mild-to-moderate hypertension: a double-blind, randomized, parallel-group study.

1. The objective of this double-blind parallel-group study was to compare the tolerability of isradipine and amlodipine, specifically, the side-effects known to be related to the use of dihydropyridine calcium antagonists. 2. A total of 205 patients with mild-to-moderate essential hypertension were randomized to receive either the sustained-release (SRO) formulation of isradipine (n = 103) or amlodipine (n = 102), both at dosages of 5 mg once daily. Blood pressure measurements were taken at the end of the dosing interval to assess the antihypertensive efficacy of the two drugs. 3. Adverse reactions were assessed in two ways: a) spontaneously reported adverse events were recorded and investigated in depth for severity, duration, relation to the study drug, and outcome; b) a questionnaire was used to elicit specific adverse reactions known to be related to the use of dihydropyridine calcium antagonists which were evaluated for severity, duration, relation to the study drug, and outcome. 4. After 6 weeks of active treatment, both isradipine and amlodipine reduced mean sitting systolic/diastolic blood pressure: from 165.1/100.1 to 145.2/89.7 mm Hg with isradipine; and from 164.1/100.6 to 145.7/90.5 mm Hg with amlodipine. There was no difference in antihypertensive effect between isradipine and amlodipine (95% CI: -3.73 to 4.73 and -1.89 to 3.49 for differences in systolic and diastolic blood pressure, respectively). 5. The number of patients spontaneously reporting adverse events was significantly higher (P = 0.02; 95% CI: 3.1 to 26.7%) with amlodipine (33.3%) than with isradipine (18.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Two-week oral treatment of tinea pedis, comparing terbinafine (250 mg/day) with itraconazole (100 mg/day): a double-blind, multicentre study.

In this randomized double-blind trial, two new antifungal compounds were compared in patients with interdigital or more extensive forms of tinea pedis. Two weeks of oral treatment with either terbinafine, an allylamine and new chemical entity, 250 mg daily, or itraconazole 100 mg daily, was given to 366 patients (184 terbinafine, 182 itraconazole). Of 13 patients who did not return after the first visit, 11 were lost to follow-up (five on terbinafine, six on itraconazole) and two reported adverse events. Another nine patients (three on terbinafine and six on itraconazole) were excluded because it was uncertain to which group they were randomized. A central laboratory performed both the mycology and safety tests. In 355 patients who received the study medications and were available for analysis of side-effects, 18 out of 179 (10.0%) in the terbinafine group and 10 out of 176 (5.7%) in the itraconazole group reported adverse events. No new clinically significant laboratory abnormalities were seen after treatment. At week 8 the efficacy analysis in 117 patients with mycologically confirmed dermatophyte infections (51 on terbinafine, 66 on itraconazole) showed that clinical symptoms were absent or minimal in 94.1% of the terbinafine and 72.7% of the itraconazole group (P = 0.0095); mycology was negative in 86.3% of the terbinafine and 54.5% of the itraconazole group (P = 0.0002). With terbinafine, negative mycology at week 8 was 81.3% in the interdigital and 88.6% in the more extensive forms of tinea pedis; with itraconazole mycology was negative in 65.0% and 50.0% of patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Tolerability of isradipine in the treatment of mild-to-moderate hypertension in general practice: a large-scale surveillance study.

The tolerability of isradipine was evaluated in an open trial of patients with mild-to-moderate essential hypertension as treated in general practice. The primary objective was to identify all adverse reactions, especially those that were newly occurring (greater than or equal to 6 reports), with a frequency greater than 1/1,000. Over 1,100 general practitioners and 5,526 patients participated in this trial. After a 2-week washout period, and a 3-week placebo run-in, patients with diastolic blood pressure (DBP) greater than or equal to 95 mm Hg were initially given isradipine at 1.25 mg twice daily. After 4 weeks, doses were doubled if DBP was greater than 90 mm Hg. If, after a further 4 weeks with doubled dosages, the DBP was still greater than 90 mm Hg, a second (nonspecified free-choice) antihypertensive agent was added to the treatment. Adverse events were recorded by open questioning. The incidence of adverse events was found to be similar to that with placebo; adverse events were generally mild or moderate in intensity and disappeared over time. No newly occurring adverse events were found. In conclusion, isradipine is safe and well tolerated at effective antihypertensive doses in patients with mild-to-moderate hypertension as treated in general practice.

Long-term (2-year) isradipine data in the treatment of mild-to-moderate hypertension.

At the end of a short-term (3-month) study of antihypertensive treatment of mild-to-moderate hypertension, 141 of the 200 study patients continued into a 2-year follow-up of isradipine as monotherapy or in combination with other antihypertensive agents. Although all 141 patients completed the first year, only 102 completed the study. Twenty-four patients dropped out: 2 with flushing; 1 each with arrhythmia, edema, angina, and headache; 12 who were noncompliant; 2 with disease unrelated to the study drug; and 4 for reasons unknown. Before the follow-up, 70% of the 141 patients were taking isradipine; after 2 years, 63% were still taking isradipine as monotherapy. During the follow-up study, the blood pressure remained stable (142.9/86.8 mm Hg after 3 months, and 142.9/86.2 mm Hg after 2 years), whereas the normalization rate was only slightly changed (73 vs. 75.2%). The incidence of reported adverse events decreased with time. At the end of the short-term study, 44.7% of patients had reported one or more adverse events; after 2 years of treatment, only 14.4% reported adverse events. Two patients had ECG signs of left ventricular hypertrophy: one showed no relevant changes while the other presented clear signs of regression. No clinically relevant laboratory abnormalities were noted during the study. In conclusion, isradipine is effective, well tolerated and safe in the long-term treatment of mild-to-moderate hypertension.

The efficacy of bromocriptine in benign prostatic hypertrophy. A double-blind study.

The efficacy and the safety of bromocriptine 7.5 mg daily were investigated in a double-blind versus placebo trial in 32 patients with troublesome symptoms from benign prostatic hypertrophy. Differences between the treatments in respect of uroflowmetry, residual urine and safety parameters were not statistically significant. Differences in respect of nocturia, daytime frequency and overall efficacy were statistically significant in favour of bromocriptine. There could be a place for bromocriptine in the palliative treatment of the functional disability caused by benign prostatic hypertrophy when surgery is refused or contraindicated.

Inhibition of puerperal lactation by means of a single injection of bromocriptine retard.

The efficacy, tolerance and acceptability of a single i.m. injection of 50 mg bromocriptine retard (in polylactic acid microspheres), given within 12 h after delivery for suppression of lactation, were investigated in 47 mothers not willing to breast-feed. Slight to moderate breast discomfort was noticed during the first postpartum days in 23% of the patients but lactation was indeed prevented in all cases and no rebound lactation occurred in any case. Only six patients exhibited at least two symptoms of mammary engorgement (congestion and pain or milk let-down): in this group, blood mean PRL levels were significantly less suppressed on postpartum days 2, 6, 21 and 28 (p less than 0.05 to p less than 0.001) than in the group of mothers completely free of any mammary symptoms. Slight side-effects (mostly dizziness), as mentioned at systematic request, were recorded in 34% of the patients; only 3 patients required treatment for their side-effects. Recovery of ovarian function was evident quite early (by day 28 in 72% of the patients), thus requiring early onset of contraception.