tropisetron and Neoplasms--Germ-Cell-and-Embryonal

To compare the antiemetic efficacy and tolerability of tropisetron plus metopimazine with tropisetron plus placebo during 4 cycles of multiple-day, cisplatin-based chemotherapy.. 82 chemotherapy-naive patients with germ cell cancer scheduled to 4 cycles of multiple-day cisplatin-based chemotherapy (20 or 40 mg/m(2)/day for 5 days) given every 3 weeks were included. A double-blind parallel trial design was used and patients randomized to tropisetron plus metopimazine or tropisetron plus placebo. Tropisetron was administered as a single 5 mg intravenous dose on days 1-5 and a single 5 mg oral dose on day 6, and metopimazine as 30 mg orally t.i.d. on day 1, and q.i.d on days 2-6.. Patients were evaluable for efficacy during a total of 195 cycles. Small, but certain advantages were obtained with the combination. In cycle 1, complete protection from emetic episodes on day 1, days 1-5, days 6-9 and days 1-9 was achieved in 85.7%, 42.9%, 86.2% and 40.5% with tropisetron plus metopimazine and in 90.0%, 22.5%, 64.3% and 17.5% with tropisetron plus placebo, respectively. This difference achieved statistical significance in the overall period, days 1-9 (P = 0.029). During the entire period (days 1-9), significantly less nausea was seen in patients receiving tropisetron plus metopimazine (P = 0.027), whereas other nausea parameters did not reach statistical significance. The cumulative emetic protection rate after 4 cycles was 0.51 with tropisetron plus metopimazine and 0.25 with tropisetron plus placebo (P = 0.037). Side effects were generally few and mild with both treatments and no significant differences were seen.. Tropisetron plus metopimazine is superior to tropisetron during 4 cycles of multiple-day cisplatin-based chemotherapy, but both treatments are ineffective in a number of patients. The effect of the combination seems comparable to that of ondansetron plus dexamethasone. Newer drugs such as the neurokinin(1) receptor antagonist, aprepitant, should be investigated to optimize antiemetic therapy in patients receiving multiple-day chemotherapy.

Topics: Adolescent; Adult; Antiemetics; Antineoplastic Agents; Cisplatin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Indoles; Isonipecotic Acids; Male; Middle Aged; Nausea; Neoplasms, Germ Cell and Embryonal; Tropisetron; Vomiting

The administration of platinum-based chemotherapy induces serotonin release from the enterochromaffin cells, causing nausea and vomiting. This study was conducted to evaluate parameters of serotonin metabolism following platinum-based chemotherapy given in combination with the serotonin type-3 antagonist tropisetron as an antiemetic agent. In nine chemotherapy-naive patients with disseminated germ-cell tumors, parameters of serotonin metabolism in both blood and urine were evaluated during two consecutive courses of platinum-based chemotherapy. Serotonin concentrations in platelet-rich plasma and platelet-poor plasma as well as urinary 5-hydroxyindoleacetic acid (5-HIAA) and serotonin levels were measured during the full length of the courses. By means of comparison with the antiemetic agent chlorpromazine, used on day 1 of the first course only, the effect of the serotonin type-3 antagonist tropisetron, the antiemetic agent used during the rest of the courses, on these parameters was studied. Clinical effects were also recorded. No change in the parameters of serotonin metabolism could be demonstrated during either course by the serotonin type-3 antagonist tropisetron. Also in vitro, no effect of tropisetron on the active serotonin uptake by platelets was found. Serotonin levels in platelets showed no correlation with emetic response. However, the platelet serotonin content decreased significantly between the first and the second course (P < 0.01). The significant reduction in platelet serotonin content observed between the first and the second course indicates a depletion of total body serotonin. The role of a serotonin type-3 antagonist might be affected by the altered serotonin equilibrium during later courses of chemotherapy.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chlorpromazine; Cisplatin; Drug Interactions; Etoposide; Humans; Hydroxyindoleacetic Acid; Indoles; Infusions, Intravenous; Neoplasms, Germ Cell and Embryonal; Serotonin; Serotonin Antagonists; Tropisetron; Vomiting