tropisetron and Head-and-Neck-Neoplasms

To assess, in a prospective, observational study, the safety and efficacy of the addition of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant to concomitant radiochemotherapy, for the prophylaxis of radiation therapy-induced nausea and vomiting.. This prospective observational study compared the antiemetic efficacy of an NK1-RA (aprepitant), a 5-hydroxytryptamine-RA, and dexamethasone (aprepitant regimen) versus a 5-hydroxytryptamine-RA and dexamethasone (control regimen) in patients receiving concomitant radiochemotherapy with cisplatin at the Department of Radiation Oncology, University Hospital Halle (Saale), Germany. The primary endpoint was complete response in the overall phase, defined as no vomiting and no use of rescue therapy in this period.. Fifty-nine patients treated with concomitant radiochemotherapy with cisplatin were included in this study. Thirty-one patients received the aprepitant regimen and 29 the control regimen. The overall complete response rates for cycles 1 and 2 were 75.9% and 64.5% for the aprepitant group and 60.7% and 54.2% for the control group, respectively. Although a 15.2% absolute difference was reached in cycle 1, a statistical significance was not detected (P=.22). Furthermore maximum nausea was 1.58 ± 1.91 in the control group and 0.73 ± 1.79 in the aprepitant group (P=.084); for the head-and-neck subset, 2.23 ± 2.13 in the control group and 0.64 ± 1.77 in the aprepitant group, respectively (P=.03).. This is the first study of an NK1-RA-containing antiemetic prophylaxis regimen in patients receiving concomitant radiochemotherapy. Although the primary endpoint was not obtained, the absolute difference of 10% in efficacy was reached, which is defined as clinically meaningful for patients by international guidelines groups. Randomized phase 3 studies are necessary to further define the potential role of an NK1-RA in this setting.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Chemoradiotherapy; Cisplatin; Dexamethasone; Drug Therapy, Combination; Esophageal Neoplasms; Female; Head and Neck Neoplasms; Humans; Indoles; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Ondansetron; Prospective Studies; Serotonin Antagonists; Tropisetron; Uterine Cervical Neoplasms; Vomiting

The purpose of this study was to compare the antiemetic efficacy of three 5-HT3 antagonists (granisetron, ondansetron, tropisetron) plus dexamethasone for the prevention of acute emesis induced by high-dose cisplatin chemotherapy. This was a randomized, open label, crossover study. Recruited into the study were 94 chemotherapy-naive patients of whom five were excluded because chemotherapy was not given, noncisplatin regimen was used instead, or presence of anticipatory vomiting. The remaining 89 evaluable patients were mostly (86.5%) male, and were all treated for head and neck cancers. The antiemetic regimens consisted of 1) granisetron 3 mg i.v. and dexamethasone 20 mg i.v. on day 1 (GRADEX); 2) tropisetron 5 mg i.v. and dexamethasone 20 mg i.v. on day 1 (TRODEX); and 3) ondansetron 8 mg i.v. and dexamethasone 20 mg i.v. to be followed by ondansetron 8 mg p.o. x 2 on day 1 (ONDEX). Patients were randomized to receive one of the three regimens in the first cycle, and treatment was crossed over to the other two regimens in subsequent cycles. Antiemetic efficacy was assessed using self-report diaries recording the number of vomiting episodes as well as duration and severity of nausea within the first 24 hours. Complete response was defined as no vomiting with or without mild nausea, and major response was defined as one vomiting episode and/or moderate to severe nausea. Major efficacy refers to either complete or major response. A total of 219 cycles was given to 89 patients: 16 received one cycle only, 16 received two cycles, and 57 received three cycles. No carryover effects were observed between cycles. Using pooled data from all cycles, the complete response rates to GRADEX, TRODEX, and ONDEX were 81%, 68%, and 71%, respectively (p = 0.11); the corresponding major efficacy rates were 91%, 93%, and 86%, respectively (p = 0.36). When only the first cycle was considered, the complete response rates to GRADEX, TRODEX, and ONDEX were 81%, 75%, and 74%, respectively (p = 0.58); the corresponding major efficacy rates were 92%, 94%, and 84%, respectively (p = 0.38). Analysis of the crossover data showed that the majority of patients achieved complete response or major efficacy with the different pairs of regimens, and there were no significant differences between different regimens in terms of complete response or major efficacy. The only exception was GRADEX versus TRODEX, in which 15.5% of patient achieved complete response with GRADEX as compared with 1.7%

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Cisplatin; Cross-Over Studies; Dexamethasone; Female; Granisetron; Head and Neck Neoplasms; Humans; Indoles; Injections, Intravenous; Male; Middle Aged; Ondansetron; Patient Satisfaction; Treatment Outcome; Tropisetron; Vomiting

A single-institution, prospective, randomized, open controlled trial was carried out on head and neck cancer patients to compare granisetron (GRA), ondansetron (OND), and tropisetron (TRO) in the prevention of cisplatin-induced acute nausea and vomiting. All patients were chemotherapy-naive and treated with cisplatin on Day 1 (80 to 100 mg/m2).. One hundred seventeen patients were treated for a total of 463 cycles of cisplatin-based chemotherapy and randomized to receive 24 mg of OND intravenously (i.v.), 3 mg of GRA i.v., or 5 mg of TRO i.v. for the control of acute nausea and emesis.. In the GRA group, complete response (CR) was obtained in 119 of 165 cycles (72.1%), major response (MR) in 32 cycles (19.4%), minor response (MiR) in 5 cycles (3%), and a failure (F) in 9 cycles (5.5%). In the OND group, CR was obtained in 110 of 150 cycles (73.3%), MR in 31 cycles (20.7%), MiR in 2 cycles (1.3%), and F in 7 cycles (4.7%). In the TRO group, CR was obtained in 100 of 148 cycles (67.6%), MR in 26 cycles (17.6%), MiR in 15 cycles (10.1%), and F in 7 cycles (4.7%). Major efficacy (CR + MR) was obtained in 151 of 165 cycles (91.5%) for GRA, in 141 of 150 cycles (94.0%) for OND, and in 126 of 148 cycles (85.2%) for TRO. The difference in major efficacy between OND and TRO was statistically significant. When comparing MiR, both GRA and OND were more effective than TRO. No other significant differences were observed among the three antiemetic agents.. Although our results were achieved in an open trial, they show that GRA and OND are equally effective antiemetic agents in the prevention of cisplatin induced acute nausea and vomiting. TRO provides almost the same protection but is not as effective as OND for major efficacy. All three antiemetics can be administered safely to patients undergoing chemotherapy with cisplatin at doses of 80 mg/m2 or more.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Cisplatin; Drug Administration Schedule; Female; Granisetron; Head and Neck Neoplasms; Humans; Indoles; Male; Middle Aged; Nausea; Ondansetron; Prospective Studies; Serotonin Antagonists; Tropisetron; Vomiting

A comparative clinical trial of tropisetron capsule was conducted in three dose groups to investigate its optimal dose on nausea and vomiting induced by anti-cancer drugs, including cisplatin. The doses were randomized by the central registration office. In the assessment of clinical efficacy, cases rated as "effective" or better accounted for 61.5% of the 2.5 mg group (16/26), 80.8% of the 5.0mg group (21/26) and 80.0% of the 10mg group (24/30), respectively; the ratings for the 5mg and 10mg groups were almost equivalent, which was higher than that for the 2.5mg group. Adverse events observed were fever, diarrhea, drowsiness, headache and/or facial erythema in 4 out of 97 cases. Abnormal laboratory findings noted were 6 cases of increased GOT, GPT, LDH, total bilirubin and/or creatinine, but none of these was serious or clinically problematic in particular. On the basis of the above results, the optimal dose of Tropisetron (capsule) is considered to be 5mg once daily.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Capsules; Cisplatin; Diarrhea; Drug Administration Schedule; Female; Fever; Head and Neck Neoplasms; Humans; Indoles; Lung Neoplasms; Male; Middle Aged; Nausea; Stomach Neoplasms; Tropisetron; Vomiting

A placebo-controlled, double-blind comparative study of tropisetron capsule was conducted to assess its clinical usefulness for nausea and vomiting induced by the anticancer drug, cisplatin, at a single dose of 50 mg/m2 or higher. Either 5mg tropisetron capsule or its placebo was given orally to patients 2 hours prior to cisplatin administration; the clinical efficacy was determined the severity of nausea and the number of emesis that occurred during 24 hours after cisplatin. Tropisetron significantly exceeded the placebo in the assessment of clinical efficacy. The ratings for the tropisetron group and the placebo group were 91.7% (22/24 cases) and 25.9% (7/27 cases), respectively. Adverse events observed were one case of headache in the tropisetron group and one diarrhea in the placebo group, while neither case was serious nor clinically problematic in particular. The above results reveal that tropisetron 5 mg capsule is significantly effective in the treatment of anticancer drug-induced nausea and vomiting. It has also been confirmed that tropisetron is a useful agent without any safety problems.

Topics: Administration, Oral; Adult; Aged; Antiemetics; Capsules; Cisplatin; Double-Blind Method; Female; Head and Neck Neoplasms; Humans; Indoles; Lung Neoplasms; Male; Middle Aged; Nausea; Tropisetron; Vomiting

Fourteen cancer patients treated with cisplatin received repeated infusions of tropisetron on-demand in conjunction with emesis. In subsequent chemotherapy courses, prophylactic tropisetron was given in a dose identical to the cumulated dose in study course 1. Tropisetron in study course 1 abolished emesis after 7.5 min (5 mg). Duration of effect was more than 7 h in 50% of the patients. No relationship between dose and duration of effect was seen. After study course 2, eight of 10 patients preferred prophylactic tropisetron. Two patients with hypertension had a severe increase in blood pressure probably related to tropisetron. It is concluded that tropisetron has an instant and lasting effect on nausea and vomiting when given on-demand. The majority of patients, however, prefer prophylactic treatment. Hypertension may be a side effect from tropisetron and caution should be displayed in hypertensive patients.

Topics: Adult; Aged; Antiemetics; Cisplatin; Dose-Response Relationship, Drug; Female; Head and Neck Neoplasms; Humans; Indoles; Male; Middle Aged; Nausea; Ovarian Neoplasms; Serotonin Antagonists; Tropisetron; Vomiting

Several investigators have reported that the efficacy of 5HT3 receptor antagonists is maintained over repeated cycles of chemotherapy. These investigators presented conditional probabilities of protection. Because conditional analyses by definition only include patients with protection in previous cycles, the results are flattered.. We applied a novel statistical approach to investigate whether the efficacy of the 5HT3 receptor antagonist ICS 205-930 (tropisetron) is maintained over repeated cycles of weekly high-dose cisplatin. Overall protection was determined based on cumulative probabilities with the Kaplan-Meier method. Complete protection was calculated with a three state model for transitional probabilities. Eighty-three patients were studied.. Over six consecutive cycles, protection against both acute and delayed emesis decreased significantly. The initial complete and overall protection rates against acute emesis of 71% and 95%, respectively, decreased to 43% and 72% in the sixth cycle of chemotherapy. Similarly, the protection rates of 31% and 68% against delayed emesis decreased to 6% and 40%, respectively.. We conclude that overall and complete long-term protection is more accurately measured by cumulative probabilities than with a method that is based on conditional probabilities. Our statistical approach shows that the efficacy of 5HT3 antagonists is not maintained.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Female; Head and Neck Neoplasms; Humans; Indoles; Male; Middle Aged; Models, Statistical; Probability; Serotonin Antagonists; Tropisetron