Efficacy and tolerability of nasally administered compared to parenterally administered metoclopramide in the symptomatic treatment of chemotherapy-induced emesis in cancer outpatients. A controlled clinical study.

The clinical efficacy and tolerability of a new nasal spray formulation of metoclopramide (MTC) was evaluated in terms of its ability to prevent the nausea and vomiting induced by a moderately emetic chemotherapy (cisplatin 20 mg/m2 weekly as radioenhancer+radiotherapy for a fractionated total of 60 Gy) in 12 patients with non-small-cell lung cancer, stage IIIB. The first chemotherapy cycle was administered without any prophylaxis in order to identify those patients who experienced grade 2 nausea and/or vomiting. As prophylaxis during the second cycle, these patients were given MTC 20 mg i.v. at time zero, and MTC 20 mg i.m. after 4 h and 8 h; during the third cycle, they received MTC 40 mg by nasal spray 2 h before chemotherapy, followed by the same dose at 4 h and 8 h. The two prophylactic treatments (parenteral injections and nasal spray) proved to be therapeutically equivalent: complete protection, 6 and 6 patients respectively; major protection, 2 and 3 patients; minor protection, 1 and 1 patient; no protection, 3 and 2 patients. The control of nausea was satisfactory, with 7 and 9 patients respectively experiencing grade 0-1 nausea. Comparative analysis of individual responses confirmed the similar anti-emetic efficacy of the two regimens. No adverse reactions were observed at any time during the course of the study, and all 12 patients judged the acceptability of the new formulation as optimal. It can thus be concluded that the use of metoclopramide nasal spray represents an effective, safe, easily managed and low-cost therapeutic alternative for the prophylaxis and treatment of emesis induced by low-dose chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics and bioavailability of metoclopramide nasal spray versus metoclopramide intravenous in healthy volunteers and cancer patients.

The kinetics and bioavailability of a new formulation of metoclopramide (CAS 364-62-5) nasal spray (MTC NS) were assessed in two separate studies versus the same drug administered intravenously (MTC IV) according to a balanced-block design where each study subject served as his own control. The first study involved 10 healthy subjects, each receiving metoclopramide NS 20 mg (one 10-mg puff per nostril) and metoclopramide IV 20 mg on two trial days separated by a 7-day washout period. On both occasions, blood samples were obtained at time 0 and at 20, 40, 60, 120, 150, 210, 280 and 360 min of dosing. Metoclopramide concentrations were assayed in plasma by HPLC. The second study involved 10 patients of oncologic domain, scheduled to receive mildly emetic chemotherapy regimes. The experimental design was similar to the one above except that blood was sampled at 0, 20, 40 and 60 min and again at 2, 3, 4, 6, and 8 h of dosing. All healthy subjects completed the trial without experiencing any adverse or untoward events; in the group of cancer patients, one subject dropped out after the nose spray treatment when he was removed to another department. This patient was replaced by another, and included in final data analysis only for the segment of treatment actually received. Metoclopramide kinetics after intravenous dosing were in good agreement with known data for the active substance, with no meaningful differences between healthy subjects and cancer patients. With MTC NS administration there was only a slight but significant difference of Cmax, being lower in the cancer patient group (p < 005).(ABSTRACT TRUNCATED AT 250 WORDS)

Concurrent carboplatin (CBDCA), vindesine (VDS) and radiotherapy in stage III non small cell lung cancer (NSCLC).

AIMS: Aim of the study was to test, in a cooperative and prospective trial, the effectiveness and feasibility of a chemoradio-therapy program in stage III non small cell lung cancer (NSCLC). METHODS: The schedule consisted in carboplatin (CBDCA) 150 mg/m2/iv on days 1, 3, 5 and vindesine VDS 2.5 mg/m2/iv on days 1, 8, 15, 22 every 4 weeks for 2 cycles followed by radiotherapy 60 Gy with CBDCA 50 mg/m2 weekly as radioenhancer. The same schedule was proposed as neoadjuvant treatment in 10/47 patients (stage III A) and as exclusive treatment in 37/47 (stage III B) admitted patients. RESULTS: In the neoadjuvant subgroup partial remission was obtained in 5/10 patients, and 3 of them underwent surgery with consequent CR. In the stage III B subgroup, 2 complete remissions were obtained (survival 14 and 9+ months). Toxicity was mild. CONCLUSIONS: Our results confirm the feasibility of the schedule in stage III NSCLC.