tropisetron and Genital-Neoplasms--Female

The efficacy of an intravenous 5-HT3 antagonist (granisetron) and four oral 5-HT3 antagonists (granisetron, ondansetron, tropisetron and ramosetron) on chemotherapy-induced emesis were investigated in 21 gynecologic cancer patients (63 courses). The severity of emesis after chemotherapy was classified in 4 grades (0: none, 1: slight loss of appetite, 2: severe loss of appetite, but tolerable, and 3: untolerable). The effect of 5-HT3 antagonists was judged by both the score for the severity of the emesis and the frequency of vomiting. The four oral 5-HT3 antagonists were almost the same in efficacy for 5 days after chemotherapy. Oral 5-HT3 antagonists were almost equipotent to intravenous granisetron for JT (paclitaxel + carboplatin) therapy or T (paclitaxel) therapy for 5 days after chemotherapy. However, they were ineffective for CAP (cisplatin + adriamycin + cyclophosphamide) therapy. From these results, oral 5-HT3 antagonists were proved to have a sufficient anti emetic effect after chemotherapy in cases of JT or T therapy. However, in cases of CAP therapy, intravenous 5-HT3 antagonists were thought to be preferable for the control of emesis due to chemotherapy.

Topics: Administration, Oral; Antiemetics; Benzimidazoles; Carboplatin; Cisplatin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Genital Neoplasms, Female; Granisetron; Humans; Indoles; Middle Aged; Nausea; Ondansetron; Paclitaxel; Serotonin Antagonists; Tropisetron; Vomiting

Chemotherapy-induced emesis is one of the most disturbing side effects of cancer therapy. Control of acute emesis has improved substantially during recent years, but control of delayed emesis and nausea remains a challenging problem. The role of 5-HT3 receptor antagonists in the treatment of delayed emesis is disputed.. Tropisetron, a highly specific 5-HT3 receptor antagonist, was compared (as an adjunct to dexamethasone) with placebo in a randomized, double blind, multicenter trial for the prevention of delayed emesis during platinum-containing chemotherapy. Three hundred chemotherapy-naive women with gynecologic malignancies were included. The cisplatin dose was in the range of 50-100 mg/m2.. Acute emesis was prevented completely in 87% of patients and acute nausea in 77% of patients in the complete series. During the complete delayed period (Days 2-6), total control of emesis was achieved in 77% of the dexamethasone and tropisetron-treated patients and in 72% of the patients receiving dexamethasone and placebo (P = 0.2473). During the same period nausea was controlled completely in 42% of the dexamethasone and tropisetron group and in 41% of the dexamethasone and placebo group. On Day 3, complete protection from nausea was achieved in 65% of patients receiving tropisetron and in 51% of patients receiving placebo (P = 0.0304). Constipation occurred more frequently in the tropisetron group.. Tropisetron added to dexamethasone improved control of delayed nausea on Day 3 compared with placebo. No significant differences were recorded regarding control of delayed emesis.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Drug Tolerance; Female; Genital Neoplasms, Female; Humans; Indoles; Middle Aged; Nausea; Serotonin Antagonists; Time Factors; Tropisetron; Vomiting

Cisplatin-induced emesis is one of the most feared side effects in cancer treatment. High-dose metoclopramide may prevent only 30-40% of cases of acute emesis. Investigations to test the efficacy of new antiemetics are mandatory. We compared the efficacy, toxicity, and patients' preference for tropisetron, a new 5-hydroxytryptamine3 (HT3) receptor antagonist, with those of a combination of high-dose metoclopramide, dexamethasone, diphenhydramine, and lorazepam (metoclopramide cocktail) in a randomized crossover study for the control of nausea and vomiting during cisplatin-containing chemotherapy. A total of 62 chemotherapy-naive women were included and followed over 3 consecutive courses. Detailed analysis comparing the incidence of acute emesis for each 4 h period following cisplatin infusion was also performed. Complete protection from acute emesis was obtained in 48% of patients receiving tropisetron and 29% of patients receiving the metoclopramide cocktail over the first two courses of chemotherapy (P = 0.029). When the frequency of acute emesis in all patients was compared on a daily basis, no significant difference was found. When emesis frequency was compared over each 4 h period following infusion of cisplatin, tropisetron was superior to the metoclopramide cocktail during the first, the second, and the first and second periods (P = 0.0001, P = 0.01 and P = 0.0006, respectively). This superiority reversed after 12 h but did not reach statistical significance (P = 0.112). Tropisetron was more effective in controlling acute nausea, but metoclopramide provided better control of delayed emesis. A drop in efficacy over successive courses was observed in patients receiving metoclopramide first but was not seen in tropisetron-first patients. A tendency for tropisetron preference was observed. Tropisetron is more effective than the metoclopramide cocktail in the control of chemotherapy-induced vomiting within 8 h of the implementation of cisplatin and in the control of nausea on the 1st day. To improve the control of chemotherapy-induced emesis, further investigations on the additional tropisetron dosing at 8 h after cisplatin infusion or the combination use of tropisetron and other antiemetics by a continuous 4 h period of observation and comparison are mandatory.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Cisplatin; Cross-Over Studies; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Humans; Indoles; Metoclopramide; Middle Aged; Nausea; Severity of Illness Index; Time Factors; Tropisetron; Vomiting

In a double-blind, randomised, multicentre study, the efficacy and tolerability of tropisetron and a combination of tropisetron and dexamethasone were compared for the control of nausea and vomiting induced by cisplatin in patients previously not entirely protected by tropisetron monotherapy. In all, 160 women with gynaecological cancers were studied during two consecutive courses of cisplatin-containing chemotherapy. During the first course (the screening course), all patients received tropisetron monotherapy [5 mg intravenous (i.v.) on day 1 and 5 mg orally on days 2-6] as antiemetic treatment. During the second course (the test course), tropisetron was compared with a combination of tropisetron and dexamethasone (20 mg i.v. on day 1 and 4.5 mg twice daily on days 2-6). This part of the study was double-blind, randomised and placebo-controlled. Candidates for randomisation were patients with partial control of nausea (< 12 h of nausea) or partial control of vomiting (1-4 episodes of vomiting) during the screening course. Patients with complete control of nausea and vomiting in the screening course continued with tropisetron monotherapy; patients with treatment failure received open rescue treatment in course 2. Total control of acute nausea was achieved in 37% of the tropisetron + placebo group and in 75% of the tropisetron + dexamethasone group (P = 0.001). Significantly more patients on tropisetron-dexamethasone than on tropisetron-placebo were also free of delayed nausea. Acute vomiting was prevented in 40% of the patients in the placebo group and in 75% in the dexamethasone group (P = 0.001). Delayed vomiting was also significantly less frequent in dexamethasone-treated patients than in placebo-treated patients. Tropisetron was well tolerated both as monotherapy and in combination with dexamethasone. The most frequent adverse events were headache (34%), constipation (12.5%) and fatigue (12.5%). Adding high doses of a corticosteroid did not induce further adverse events or disregulate concurrent diseases.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Cisplatin; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Humans; Indoles; Middle Aged; Nausea; Tropisetron; Vomiting

In a prospective randomized study comprising 66 women treated for gynecologic malignancies with cisplatin-containing chemotherapy, the new 5-hydroxytryptamine3 (5-HT3) receptor antagonist tropisetron (Navoban, Sandoz Pharma Ltd.) was compared with a metoclopramide cocktail for the prevention of nausea and emesis. All patients were chemotherapy-naive. Two consecutive courses (including the 1st week posttherapy) were studied. The cisplatin doses were in the range of 50-75 mg/m2, and the regimens also contained doxorubicin, teniposide, etoposide, vincristine, and bleomycin. Complete protection against nausea during the first 24 h (course 1) was achieved in 76% of the tropisetron group and in 85% of the metoclopramide group. Emesis was prevented in 82% of the patients in both groups. During the whole 6-day period, full emetic protection was achieved in 30% and 18% of the patients in the two groups. On days 3-4 of course 1, tropisetron was superior to metoclopramide. The overall tolerability of the tropisetron was excellent or good in 94% of patients, a rate higher than that observed for the metoclopramide regimen (75%). The most common side effects for the latter regimen were sedation (82%) and extrapyramidal reactions (21%). The only significant adverse event recorded after treatment with tropisetron was headache of slight or moderate grade.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Cisplatin; Drug Administration Schedule; Female; Genital Neoplasms, Female; Humans; Indoles; Metoclopramide; Middle Aged; Nausea; Prospective Studies; Serotonin Antagonists; Treatment Outcome; Tropisetron; Vomiting

Efficacy and safety of the antiemetic agent Navoban (5HT3-receptor-antagonist Tropisetron) on cytostatic-induced emesis of breast cancers and gynecological cancers was tested in 28 female patients receiving a total of 127 chemotherapy courses containing high (cisplatin), moderate high (cyclophosphamid) or moderate (for example 5 FU) emetogenic cytostatic drugs. We studied antiemetic response rates of Navoban (5 mg/d) during the first 24 hours after administration of the chemotherapy as well as response rates of the "delayed nausea and emesis" (days 2-9 after chemotherapy). A complete response was observed in 103 chemotherapy courses (= 81.1%) during the first 24 hours after chemotherapy and in 93 courses (= 73.2%) for the "delayed emesis". Treatment failures (more than 5 vomiting episodes) during the first 24 hours were present in four courses and for the "delayed emesis" in 11 courses. The side effects of Navoban such as constipation, headache or tiredness were minimum. Therefore no patient refused to receive the necessary chemotherapy. Navoban is, with its single dose application, an effective therapeutic drug for the prevention of nausea and emesis in patients receiving a chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Genital Neoplasms, Female; Humans; Indoles; Middle Aged; Nausea; Palliative Care; Serotonin Antagonists; Tropisetron; Vomiting