Comparison of oral 5-HT3-receptor antagonists and low-dose oral metoclopramide plus i.m. dexamethasone for the prevention of delayed emesis in head and neck cancer patients receiving high-dose cisplatin.

A phase III, single-institution, open, prospective, randomized, parallel study was carried out on head and neck cancer patients to compare a combination of low-dose (20 mg q.i.d.) oral metoclopramide (M) + i.m. Dexamethasone (D) with an oral 5-HT3-Receptor Antagonist (5-HT3-RA) alone in the prevention of high-dose (HD > or = 80 mg/m2) cisplatin-induced delayed emesis. 51 consecutive patients, all but two with advanced stage of disease, were treated for a total of 198 chemotherapic cycles: 23 patients entered Group A (5-HT3-RA) receiving a total of 108 cycles, 28 patients entered Group B (M + D) receiving a total of 90 cycles. The treatment groups were well matched for age, sex (almost all patients were males), ECOG PSR, stage of disease and alcohol intake. The efficacy of M + D was significantly higher than that of 5-HT3-RA in achieving complete protection (CR 88.9% vs 72.2%, chi2 9.9, p = 0.002) and major efficacy (ME: CR + MR) (94.5% vs 85.2%, chi2 5.6, p = 0.02). Generally, for both treatments (5-HT3-RA and M + D) a good control of delayed emesis was achieved in patients who had complete protection on acute emesis. A good control of acute emesis had a highly positive predictive value of delayed emesis for both treatments without significant difference between them (CR 85% for M + D and 82% for 5-HT3-RA; ME 88% for M + D and 92% for 5-HT3-RA). The failure (F) on acute emesis had a significantly higher negative predictive value of delayed emesis for M + D (98%) than 5-HT3-RA (67%). Our study is, to our knowledge, the first comparing M + D vs one 5-HT3-RA alone in the prevention of HD cisplatin-induced delayed emesis in a properly designed clinical trial. Our results show that M + D are more effective than 5-HT3-RA alone in the prevention of HD cisplatin induced delayed emesis, whereas 5-HT3-RA may be the treatment of choice in patients who had acute vomiting. Our study demonstrated not only the persistence of antiemetic efficacy but also increasing efficacy, during subsequent courses. Our results confirm that protection from acute emesis plays a major role in the appearance and control of delayed emesis.