The antiemetic efficacy of oral ondansetron plus intravenous dexamethasone in patients with gynecologic malignancies receiving carboplatin-based chemotherapy

PURPOSE: The purpose of this study was to develop a cost-effective prophylactic antiemetic regimen for the prevention of carboplatin-induced emesis. METHODS: Patients being treated in the Gynecologic Cancer Program of the Cleveland Clinic Taussig Cancer Center with a carboplatin-based chemotherapy regimen received a prophylactic antiemetic program consisting of a single dose of oral ondansetron (16 mg) plus intravenous dexamethasone (20 mg) approximately 30 min prior to chemotherapy. Evaluation of the effectiveness of this antiemetic regimen was performed during a single treatment course. RESULTS: A total of 27 patients (median age, 62; range, 41-83) participated in this phase 2 trial. Three patients received single-agent carboplatin, and 24 were treated with either a carboplatin/paclitaxel or carboplatin/docetaxel regimen. The carboplatin AUC dosing level was 4, 5, or 6 in 6, 5, and 16 individuals, respectively. No patient developed vomiting; 2 (7%) individuals experienced nausea during the 24-h period following chemotherapy administration. CONCLUSION: The combination of a single dose of oral ondansetron (16 mg) plus intravenous dexamethasone (20 mg) is an effective prophylactic antiemetic regimen for patients receiving carboplatin-based chemotherapy.     

Effectiveness of serotonin-receptor antagonist antiemetic therapy over successive courses of carboplatin-based chemotherapy

PURPOSE: There are extremely limited data available in the general oncology or gynecologic cancer literature to document the effectiveness of antiemetic therapy over multiple courses of cytotoxic chemotherapy. METHODS: To examine this highly clinically relevant issue, we analyzed the complete treatment course of patients with gynecologic cancers receiving carboplatin-based chemotherapy regimens who had participated in one of four institutional serotonin-receptor antagonist antiemetic trials, which had specifically evaluated the benefits of such therapy during only the first treatment course. Medical records were reviewed to examine the development of emesis during subsequent chemotherapy treatment cycles. RESULTS: The 91 patients included in this analysis received a median of 6 courses (range 1-18) of carboplatin (initial AUC dose 4, 5, and 6 in 29, 29, and 32 patients, respectively). All received ondansetron or granisetron plus dexamethasone with every treatment course. Complete control of emesis (no acute or delayed nausea or vomiting) was experienced by 56 (62%) patients during every cycle. Conversely, 20% of women noted one or more episodes of nausea without vomiting and 19% developed at least one incidence of vomiting. In no case was emesis considered to be severe (grade 3), and no patient required either discontinuation of carboplatin or a dose reduction due to the development of emesis. CONCLUSION: In the large majority of patients, serotonin-receptor antagonist antiemetic therapy, administered in combination with dexamethasone, is highly effective over multiple courses in preventing significant carboplatin-induced nausea and vomiting.     

Evaluation of the relation between patient characteristics and the state of chemotherapy-induced nausea and vomiting in patients with gynecologic cancer receiving paclitaxel and carboplatin

Purpose

An antiemetic regimen for patients taking paclitaxel and carboplatin (TC) includes dexamethasone (20 mg) to protect against hypersensitivity. Chemotherapy-induced nausea and vomiting (CINV), however, is difficult to adequately control in patients receiving TC. In the present study, we retrospectively investigated risk factors for CINV in patients receiving TC with this antiemetic regimen based on a questionnaire.

Methods

Eligible patients were diagnosed with gynecologic cancer and receiving paclitaxel (175 mg/m²) intravenously for 3 h and carboplatin (area under the curve 5 mg/mL per min) on day 1 every 3 weeks in our institution, and treated with granisetron (3 mg) and dexamethasone (20 mg) for antiemesis. Data of nausea and vomiting assessed by Common Terminology Criteria for Adverse Events version4.0 were collected from the medical records. Patients were asked to complete a questionnaire including items such as age and hyperemesis. Logistic regression analysis was used to evaluate univariate and independent multivariate associations with items on nausea of grade 2 or greater and vomiting of grade 1 or greater.

Results

On univariate logistic analysis, no item was significantly associated with nausea of grade 2 or greater. Hypertension and hyperemesis gravidarum and adjuvant chemotherapy were significantly associated with delayed vomiting of grade 1 or greater. Multivariate analysis was performed with delayed vomiting of grade 1 or greater as an endpoint, and the resulting independent items were hypertension and hyperemesis gravidarum.

Conclusions

The present study showed that the risk factor for delayed vomiting of grade 1 or higher was a history of hyperemesis gravidarum in patients receiving conventional TC with dexamethasone (20 mg) and granisetron. Therefore, in patients with this risk factor, criteria of major organizations should be followed first.     

The prevention of CDDP-induced emesis with a combination regimen including metoclopramide, dexamethasone, droperidol and diphenhydramine

The dose limiting factors of cisplatinum are nephrotoxicity and emesis. Nephrotoxicity has been reduced by hydration but nausea and vomiting caused by cisplatinum have led to refusal of potentially curative therapy by a number of patients. The prevention of nausea and vomiting by a combination of antiemetic drugs administered to ovarian patients receiving chemotherapy inducing (cisplatinum 50mg/m2, adriamycin 300 mg/m2, cyclophosphamide 300 mg/m2 and 5FU 350 mg/m2) was studied. the combination antiemetic drugs were metoclopramide (1mg/kg), dexamethasone (10mg/m2), droperidol (1mg/m2) and diphenhydramine (20mg/body). These drugs without diphenhydramine were administered intravenously 30 minutes before and 2.5 hours, 5 hours and 7.5 hours after chemotherapy. Diphenhydramine was administered intramuscularly 30 minutes before and 5 hours after chemotherapy. No vomiting was noted in 82.6% (19/23) of cases, and no patient vomited more than four times. This combination regimen provided very good protection against cisplatinum induced emesis.     

The effect of metoclopramide, dexamethasone and antihistamine in the prevention of PAC chemotherapy-induced emesis

The effect of antiemetic agents on the nausea and emesis of ovarian cancer patients treated with CDDP (45 mg/m2), ADM (45 mg/m2) and CPM (450 mg/m2) combination chemotherapy was examined in a randomized parallel study. Metoclopramide (1 mg/kg, 4 times every 2.5 hours), dexamethasone (3.8 mg, 4 times every 2.5 hours) and antihistamine (10 mg, 2 times every 5 hours) were used as antiemetic agents and these agents were gradually decreased for 5 days. The above regimen significantly suppressed the frequency and volume of vomiting on the day of the first PAC chemotherapy but showed no effect on the delayed persistent nausea during chemotherapy. The frequency and volume of vomiting on the day of chemotherapy were 1.6 times and 102 ml respectively in the antiemetic group, but 8.9 times and 352 ml, respectively, in the control group. Although this antiemetic regimen sufficiently suppressed acute drug-induced emesis during chemotherapy, delayed persistent nausea was not eliminated. We next investigated whether these combined antiemetic agents protected the quality of life of patients during maintenance chemotherapy. Our data indicated that about 2 weeks was necessary to recover health after maintenance PAC chemotherapy. These results indicated that this regimen was effective in suppressing the acute drug-induced emesis and in maintaining the quality of life following maintenance PAC chemotherapy.     

Antiemetic efficacy of high-dose metoclopramide, diphenhydramine, methylprednisolone and diazepam on chemotherapy-induced emesis in gynecological malignancy

The antiemetic efficacy of high-dose metoclopramide (MCP), diphenhydramine (DPH), methylprednisolone (MPL), and diazepam (DZP) was investigated in 40 gynecologic cancer patients for a total of 98 chemotherapy courses, treated with cisplatin (50 mg/m2). With MPL (500 mg i.v. x 2) plus DZP (5 mg i.m. x 2), no vomiting occurred in 0% and mild emesis (vomiting 1-2 times) occurred in 20% of 25 courses. With MCP (2 mg/kg i.v. x 5) plus DPH (40 mg i.v. x 3), no vomiting occurred in 35% and mild emesis occurred in 10% of 20 courses. With a combination of MCP plus DPH and MPL plus DZP, no vomiting occurred in 51% and mild emesis occurred in 25% of 53 courses. These results indicate that high-dose MCP plus DPH are effective in preventing cisplatin-induced vomiting. Furthermore, the antiemetic efficacy of MCP plus DPH (0-2 vomiting episodes: 45%) was significantly enhanced (p less than 0.05) by the combined use of MPL plus DZP (0-2 vomiting episodes: 76%).     

Does increasing the steroid dose enhance the efficacy of the antiemetic combination of granisetron and methylprednisolone in gynecologic cancer patients--a randomized study

OBJECTIVE: The authors administered two doses of oral methylprednisolone in combination with 3mg granisetron intravenously for the prophylaxis of cisplatin-induced emesis in gynecologic cancer patients. MATERIALS AND METHODS: Thirty-nine patients received 100mg (group A) and 25 received 200mg (group B) methylprednisolone in the antiemetic combination in a randomized prospective trial. RESULTS: No vomiting in 90.2 and 96.7%, one emetic episode in 3 and 1.1% and two episodes in 3 and 2.2% were detected in groups A and B, respectively. More than two emetic episodes were considered to be a failure and were observed only in group A (3.8%). There was no significant difference between the two treatment groups (P=0.3160). CONCLUSIONS: There was no evidence for enhanced antiemetic effect of elevated steroidal dose in combination with granisetron.     

Antiemetic efficacy of high-dose corticosteroids and droperidol in cisplatin-induced emesis: A controlled trial with droperidol and metoclopramide

The nausea and vomiting associated with cisplatin chemotherapy make care of the patient more difficult for nurses and physicians, can cause severe metabolic and pathologic sequelae, and preclude further courses of chemotherapy. Current reports suggest that the two most efficacious agents for antiemetic prophylaxis are metoclopramide and corticosteroids. These two agents in combination with droperidol have been compared in a randomized controlled prospective fashion. Patients had less nausea and vomiting on the steroidal regimen than the nonsteroidal regimen (P less than 0.05), and the duration of nausea and vomiting was significantly less on the steroidal regimen (P less than 0.05). Patients expressed a preference for the steroidal regimen over the nonsteroidal one and the steroidal regimen retained its antiemetic effectiveness through repeated courses of chemotherapy. The results of the study suggest that corticosteroids and droperidol are superior antiemetic agents for cisplatin-induced nausea and vomiting.     

Comparative study of dexamethasone and ondansetron for prophylaxis of postoperative nausea and vomiting in laparoscopic gynecologic surgery

Objective

To compare intravenous dexamethasone and ondansetron for the prophylaxis of postoperative nausea and vomiting (PONV), a main complaint that affects almost 40%-75% of patients undergoing laparoscopic gynecologic surgery.

Methods

In a prospective study, 93 women were divided into 3 groups receiving 4 mg of dexamethasone, 8 mg of dexamethasone, or 4 mg of ondansetron. PONV score was used for assessment during the first 24 hours after surgery.

Results

The incidence of PONV during the 24-hour postoperative period was highest in the ondansetron group (61%). In the first 3 hours, the incidence of PONV in the ondansetron group was also higher: 51.6% as compared with 22.6% and 36.6% in the dexamethasone 4 mg and 8 mg groups, respectively. The overall incidence of PONV was highest in the first 3 hours as compared with later time periods, and there was a linear trend in decreasing PONV among the groups (P = 0.017). In the dexamethasone 4 mg group, the request for a rescue antiemetic was significantly lower: 0% as compared with 6.7% and 16.1% in the dexamethasone 8 mg and ondansetron 4 mg groups, respectively.

Conclusion

Dexamethasone was found to be an efficacious and cost-effective drug for the prophylaxis of PONV.     

Dexamethasone for the prevention of nausea and vomiting after dilatation and curettage: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of dexamethasone administered intravenously at three different doses (4 mg, 8 mg, 16 mg) for the prevention of nausea and vomiting after dilatation and curettage. METHODS: In a prospective, randomized, double-masked, placebo-controlled trial, 120 women received placebo or dexamethasone intravenously at doses of 4 mg, 8 mg, or 16 mg immediately before induction of anesthesia (n = 30 in each group). Propofol-based general anesthetic was used. Emetic episodes and safety assessments were performed. To estimate a sufficient sample size, it was calculated that 30 patients per group would be required with alpha =.05 and beta =.2. RESULTS: The rate of patients who were emesis-free (no nausea, retching, or vomiting) 0-24 hours after anesthesia was 57% with dexamethasone 4 mg (P =.796), 87% with dexamethasone 8 mg (P =.005), and 87% with dexamethasone 16 mg (P =.005), compared with placebo (50%). Patients who had received dexamethasone 8 mg or 16 mg were more satisfied than those who had received placebo (P <.05). No clinically important adverse events were observed in any of the groups. CONCLUSION: Dexamethasone 8 mg is an effective antiemetic for preventing postoperative nausea and vomiting 0-24 hours after anesthesia in women undergoing propofol-based general anesthesia for termination of pregnancy. Increasing the dose to 16 mg provided no additional benefit.     

Prochlorperazine and transdermal scopolamine added to a metoclopramide antiemetic regimen. A controlled comparison

Cisplatin-induced nausea and vomiting occurs both acutely and over a prolonged period of time. These symptoms may be incapacitating and are frequently given as a reason to discontinue therapy. We compared prochlorperazine and transdermal scopolamine when added to a standardized metoclopramide antiemetic regimen. Twenty-seven patients receiving cisplatin at 100 mg/m2 were randomly assigned to one of the two treatment arms. Patients were observed during chemotherapy and answered a standard questionnaire 24-26 hours later. Among similar treatment groups no differences were seen regarding the number of emetic events, level of nausea, degree of sedation or overall acceptability of one treatment arm or another. While not superior to prochlorperazine, transdermal scopolamine is a useful antiemetic agent and can be combined with metoclopramide in an attempt to reduce cisplatin-induced nausea and vomiting. Further evaluation of this approach is needed.     

A randomized blinded study of the incidence of postoperative nausea and vomiting in women after major gynecologic laparoscopic surgery

STUDY OBJECTIVE: To estimate the incidence of postoperative nausea and vomiting (PONV) in women undergoing major gynecologic laparoscopic surgery with an expected surgical duration exceeding 1 hour and anticipated overnight hospitalization. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: This study was set at a university hospital. PATIENTS: One hundred forty female patients with an American Society of Anesthesiology (ASA) physical status I or II and scheduled for gynecologic inpatient laparoscopic surgery. INTERVENTIONS: Patients were randomly assigned to receive 1 mg granisetron (Group A, n=70), or saline solution (Group B, n=70) intravenously after induction of general anesthesia. MEASUREMENTS AND MAIN RESULTS: The endpoints were evaluated by the following parameters: the incidence of PONV, episodes of nausea, retching, vomiting, rescue antiemetics, and complete response. Patients were closely observed for 24 hours after administration of the study drug. The two groups were generally well balanced in terms of demographic variables. The surgical period was longer in the granisetron group compared with the saline solution group. The total incidence of PONV was 41/70 (59%) in patients who underwent inpatient gynecologic laparoscopic surgery when no prophylactic antiemetic was given. Administration of granisetron decreased the incidence of PONV (29/70 [41%] vs 41/70 [59%], p<.05), the incidence of vomiting (18/70 [26%] vs 31/70 [44%], p<.05), and the proportions of patients requiring rescue antiemetics (14/70 [20%] vs 47/70 [67%], p<.01), but these results were not comparable to other studies. CONCLUSION: A long surgical period may have great impact on the PONV in women who undergo gynecologic laparoscopic surgery, which implies the need for skilled gynecologic laparoscopists.     

Antiemetic effect of ginger in gynecologic oncology patients receiving cisplatin

To determine whether ginger had antiemetic effect in cisplatin-induced emesis, we conducted a randomized, double-blinded crossover study in 48 gynecologic cancer patients receiving cisplatin-based chemotherapy. Subjects were randomly allocated to regimen A or regimen B in their first cycle of the study. All patients received standard antiemetics in the first day of cisplatin administration. In regimen A, capsules of ginger root powder were given orally 1 g /day for 5 days, starting on the first day of chemotherapy. In regimen B, placebo was given on the first day and metoclopramide was given orally thereafter for 4 days. The patients were then crossed over to receive the other antiemetic regimen in their next cycle of chemotherapy. Among 43 evaluable patients who received both cycles of treatment, success in controls of nausea and emesis were not significantly different between the two regimens in both acute and delayed phases. Restlessness, as a side effect, occurred more often in metoclopramide arm compared to ginger arm (P=0.109). In conclusion, addition of ginger to standard antiemetic regimen has no advantage in reducing nausea or vomiting in acute phase of cisplatin-induced emesis. In delayed phase, ginger and metoclopramide have no statistically significant difference in efficacy.     

Antiemetic combination for PAC (cisplatin-adriamycin-cyclophosphamide) chemotherapy-induced emesis in ovarian cancer

Twenty-six patients suffering from disseminated epithelial ovarian cancer (FIGO stages III and IV) under treatment with Cisplatin (80-100 mg/m2 in 8 hours) in combination on the same day with Cyclophosphamide (500 mg/m2 IV) and Adriamycin (50 mg/m2), a severely emetogenic regimen, entered a randomized, double-blind, cross-over trial comparing the antiemetic activity of high-dose IV Metoclopramide (1 mg/kg/dose X 5 doses) with that of a combination of Metoclopramide (same schedule) plus Nortriptyline (50 mg PO X 2 doses) plus Thiethylperazine (10 mg IV X 3 doses). The antiemetic combination was designed in an attempt to act simultaneously on gastrointestinal motility and neuroreceptors at the central emetic pathways (dopamine D-2, histamine H-1 and muscarinic cholinergic). This combination significantly reduced the emesis due to chemotherapy when compared with Metoclopramide alone and was also preferred by a significant number of patients after passing through both the antiemetic arms being compared.     

Randomized, Placebo-Controlled Trial of Granisetron for Control of Nausea and Vomiting During Cesarean Delivery Under Spinal Anesthesia

Objective(s)

The objective of this study was to evaluate the efficacy and safety of granisetron (5HT₃ receptor antagonist) on the incidence of nausea and vomiting in cesarean deliveries under spinal anesthesia.

Method(s)

In the randomized, double-blind study, 80 parturients received granisetron 40 μg/kg or placebo (n = 40 each) intravenously, immediately after clamping of the fetal umbilical cord. Nausea, vomiting, and adverse events were then observed for 24 h after administration of spinal anesthesia.

Results

A complete response (defined as no postoperative nausea and vomiting) during 0–4 h after administration of spinal anesthesia was achieved in 80 % of patients with granisetron and in 45 % of patients with placebo. The corresponding incidences during (4–24 h) were 82.5 and 55 % (P value <0.05). No difference in adverse events was observed in any of the groups.

Conclusion(s)

Prophylactic use of granisetron is effective for preventing emetic episodes during spinal anesthesia for cesarean delivery.     

Experience with the management of neutropenia in gynecologic cancer patients receiving carboplatin-based chemotherapy

Objective. There exists limited information in the medical literature regarding the incidence and severity of carboplatin-associated neutropenia, outside the setting of a clinical trial. We wished to examine this issue in a large single institution experience involving patients receiving both single agent and combination carboplatin-based chemotherapy for management of a female pelvic malignancy. Patients and methods. The medical records of women with gynecologic cancers treated with carboplatin-based chemotherapy at the Cleveland Clinic from January 1, 1998 through December 31, 2002 were retrospectively reviewed to determine the incidence and severity of neutropenia. Results. During the time period encompassed by this analysis, a total of 323 patients received 2145 cycles of carboplatin-based chemotherapy (total of 441 courses; median cycles/patient: 6 [range 1-27]). The total number of each program utilized, and the incidence of grades 3 and 4 neutropenia observed (lowest nadir/regimen), were as follows: single agent carboplatin (178 courses; 5% grade 3, and <1% grade 4), carboplatin/paclitaxel (198; 23% and 6%), carboplatin/docetaxel (42; 17% and 73%) and carboplatin/paclitaxel/irinotecan (23; 39% and 61%). Febrile neutropenia was uncommon, and there was only a single neutropenic-related death. Conclusion. Both single-agent carboplatin and carboplatin/paclitaxel result in a very low incidence of grade 4 neutropenia. While combining docetaxel with carboplatin or adding a "third drug" to carboplatin/paclitaxel substantially increases the incidence of severe neutropenia, neutropenic fever, and required hospitalizations for septic episodes are uncommon. The prophylactic oral administration of a broad-spectrum antibiotic (e.g., ciprofloxicin) in the presence of grade 4 neutropenia appears to be an effective strategy to minimize the risk of subsequent febrile events.     

5-Fluorouracil (5-FU) and leucovorin in platinum-refractory advanced stage ovarian carcinoma.

Twenty-nine patients with recurrent advanced stage ovarian cancer were treated with 5-fluorouracil (5-FU) and leucovorin by intravenous bolus on 5 consecutive days, repeated every 3 weeks. Twenty-one of these patients had experienced disease progression while receiving a cisplatin- or carboplatin-based regimen. There were 2 clinical complete responders and 1 partial responder to therapy (10% response rate; 95% confidence interval, 2 to 27%) and 11 individuals who experienced stable disease for periods ranging from 5 to 27 months. Of 204 cycles of therapy administered, 9 cycles were associated with hospitalization. These occurred in the more heavily pretreated members of the cohort. 5-FU and leucovorin appear to have activity in platinum-refractory ovarian cancer and form a well-tolerated regimen in most patients.     

The feasibility of carboplatin-based intraperitoneal chemotherapy in ovarian cancer

Objective

To reduce toxicities in cisplatin-based intraperitoneal (IP) chemotherapy, we substituted carboplatin for cisplatin. The purpose of this study was to provide preliminary toxicity data of carboplatin-based IP chemotherapy and to evaluate the feasibility of this chemotherapy regimen in patients with ovarian cancer after primary debulking surgery.

Study design

The toxicity data of 19 primary ovarian cancer patients (IP group) who underwent carboplatin-based IP and intravenous (IV) combination chemotherapy (IP carboplatin AUC 5 on day 1, IV paclitaxel 175 mg/m² on day 2, and IP paclitaxel 60 mg/m² on day 8) after primary debulking surgery were retrospectively analyzed and compared to 34 patients (IV group) who were treated with standard platinum-based IV chemotherapy during the same period.

Results

The toxicity data in a total of 118 cycles were analyzed. Grade 3 or 4 leukopenia, neutropenia, and pain were more common in the IP group than the IV group. There were seven catheter-related complications. Fourteen patients (73.7%) were able to complete six cycles or more of IP chemotherapy. Survival results in the IP group were compared with those from the IV group; a prolonged progression-free survival was observed (26.6 vs. 20.7 months; p = 0.038). Compared to the previous results with cisplatin-based IP chemotherapy, there was no significant difference in hematologic events. However, gastrointestinal, neurologic, and metabolic events in this study were definitely lower compared to those of cisplatin-based IP chemotherapy.

Conclusions

Carboplatin-based IP and IV combination chemotherapy is feasible in patients with ovarian carcinoma after primary debulking surgery.     

Phase I trial of escalating doses of topotecan in combination with a fixed dose of pegylated liposomal doxorubicin in women with müllerian malignancies

Background. Topotecan and pegylated liposomal doxorubicin (Doxil) interact with topoisomerase I and II (topo I and II), respectively, with schedule dependent, and potentially synergistic cytotoxicity.Objectives. Define dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) of topotecan delivered by 72-h infusion administered immediately after Doxil delivered at a fixed dose (30 mg/m²) in a cohort of women with recurrent müllerian malignancies.Methods. Topotecan dose was escalated from 0.5 mg/m²/day for 3 days in 0.2 mg/m²/day increments with treatment repeated every 21 days. Eligibility criteria required ECOG ≤2 and no more than four prior lines of chemotherapy. No dose reductions were allowed in the first two cycles to allow evaluation of cutaneous toxicity.Results. Between November 2000 and August 2002, 18 patients were enrolled. Median age 59 (40–71) years. Patients received a median 1 (1–6) cycles of chemotherapy, with 39 cycles of treatment delivered at DL 1. All patients were evaluable for toxicity and 12 for response. At dose level 2, dose-limiting toxicity consisted of nausea and vomiting, mucositis, cutaneous toxicity, and neutropenia. There was no clinically significant cardiac toxicity. There were no radiologically confirmed partial responses.Conclusions. Doxil 30 mg/m² and topotecan 0.5 mg/m²/day by 72-h infusion (total dose 1.5 mg/m²), although a rational combination of cytotoxic therapies, have limited clinical activity.     

Betamethasone-dixyrazine versus betamethasone-metoclopramide as antiemetic treatment of cisplatin-doxorubicin-induced nausea in ovarian carcinoma patients

In a prospective and randomized pilot study two antiemetic regimens comprising dixyrazine (240 mg) and metoclopramide (10 mg/kg) in high doses and given by continuous i.v. infusion were compared as means of preventing cisplatin-doxorubicin-induced nausead and vomiting. Twenty chemotherapy-naive women with the diagnosis of ovarian carcinoma stages III-IV (FIGO) were included in the study. Medium doses (50 mg/m2) of cisplatin and doxorubicin were used. The antiemetic drugs (the above-mentioned ones plus betamethasone 20 mg, and biperiden 5 mg) were administered by small portable infusion pumps during 24 hours. The effects and adverse reactions were evaluated during the course of chemotherapy and the first week thereafter. Complete protection from nausea during the first 24 hours was achieved in 80% by the metoclopramide cocktail and in 50% by the dixyrazine combination. During days 2-7 there were no significant differences between the two regimens. Vomiting was not satisfactorily prevented by either treatment. Sedation was significantly more common after dixyrazine than after metoclopramide but other recorded side effects were similar for the two antiemetic regimens. Serum concentrations of dixyrazine and metoclopramide were determined.