ramosetron, aprepitant and dexamethasone (rad) in solid cancer

Conditions: Solid Tumour; Postoperative Nausea and Vomiting

Summary: cisplatin is one of the most emetogenic drugs used in clinical practice and it could result in poor compliance with chemotherapy. the 5-ht3 receptor antagonists prevent vomiting in acute phase emesis after chemotherapy in 73 - 92% of cisplatin-treated patients when coadministered with steroids, but they appear to lack efficacy in the delayed phase emesis. ramosetron, a new 5-ht3 receptor antagonists, has been shown to have equivalent efficacy and tolerability and a longer duration of effect than granisetron in preventing acute vomiting in patients undergoing cisplatin-containing chemotherapy. acute phase emesis was prevented in 84.8% of patients receiving ramosetron plus dexamethasone, but the cr rate of total phase emesis was less than 60%. aprepitant is a selective, high-affinity nk1 receptor antagonist. adding aprepitant to 5-ht3 receptor antagonists and steroid improve cr rate of not only chemotherapy induced acute emesis and but also delayed emesis by 11-14 and 20 percentage points, respectively. but until now, there was no information that which 5-ht3 receptor antagonists is the best partner for aprepitant. therefore, we initiated a prospective, open-label, phase ii study to assess the efficacy and tolerability of a combination of ramosetron, aprepitant and dexamethasone (rad) in the prevention of cisplatin based cinv in chemotherapy-naïve patients with solid cancer

cisplatin is one of the most emetogenic drugs used in clinical practice and it could result in poor compliance with chemotherapy. the 5-ht3 receptor antagonists prevent vomiting in acute phase emesis after chemotherapy in 73 - 92% of cisplatin-treated patients when coadministered with steroids, but they appear to lack efficacy in the delayed phase emesis. ramosetron, a new 5-ht3 receptor antagonists, has been shown to have equivalent efficacy and tolerability and a longer duration of effect than granisetron in preventing acute vomiting in patients undergoing cisplatin-containing chemotherapy. acute phase emesis was prevented in 84.8% of patients receiving ramosetron plus dexamethasone, but the cr rate of total phase emesis was less than 60%.

Eligibility criteria:
inclusion criteria: * 18 -75 years, both sex * ecog performance status 0-2 * histologically proven solid cancer, chemotherapy-naïve patient * planed to receive cisplatin (≥ 50mg/m2) based, single day chemotherapy, * no nausea or vomiting within 72 hours prior to chemotherapy * serum cr \< 2.5 mg/dl, or calculated ccr ≥ 50 ml/min * serum total bilirubin \< 2 mg/dl, ast/alt \< 3 times the upper normal limit , alp \< 5 times the upper normal limit * absolute neutrophil count ≥ 1,500/μl, platelet ≥ 100,000/μl * expected life duration ≥ 3 months * patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of the hospital exclusion criteria: * patients with active infection, severe heart disease, uncontrollable hypertension or diabetes mellitus, active gastric or duodenal ulcers, or pregnancy or breast-feeding * patients who should take steroid, antiemetics, pimozide, terfenadine, astemizole, cisapride, rifampin, carbamazepine, phenytoin, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir or nelfinavir for the treatment of other diseases * patients taking any medicine, which could affect study results, within 1 week before chemotherapy (or taking anti-emetics within 48 hours before chemotherapy). prior to beginning chemotherapy, single-agent benzodiazepines as hypnotic is allowed, but it can't be receiving during day 1-6 of 1st chemotherapy cycle. * patients with symptomatic brain metastasis * patients with gi obstruction or other diseases that could provoke nausea and vomiting * patients receiving rt on brain, abdomen or pelvis within 2 weeks before chemotherapy * patients who cannot understand informed consent or express his/her condition * patients who cannot swallow drugs * patients who have known allergy or severe side effect on study drugs

Keywords: ramosetron aprepitant dexamethasone cancer chemotherapy antiemetics cisplatin nausea vomiting high dose cisplatin