[A late phase II clinical study of RP56976 (docetaxel) in patients with advanced or recurrent gastric cancer: a cooperative study group trial (group B)].

A late phase II clinical study of RP56976 (docetaxel) in patients with advanced or recurrent gastric cancer was performed to evaluate the anti-tumor activity and clinical toxicity as a multicenter cooperative trial. Docetaxel was administered intravenously at a dose of 60 mg/m2 every 3-4 weeks. Of 72 patients enrolled, 63 patients were eligible and 59 patients were evaluable for response. The anti-tumor effects obtained complete response (CR) in one patient partial response (PR) in 13, minor response (MR) in 3, no change (NC) in 20, and progressing disease (PD) in 22 patients. The overall response rate in 59 patients was 23.7% (14/59). For 14 CR or PR cases, a response appeared 10 to 107 days (median 33.5 days) and 1 to 8 (median 2) times of dosing after the initial administration. The response rate was 9.5% in the primary tumor, 31.3% livers, 50.0% abdominal tumor, and 24.1% lymph nodes, respectively. The major adverse reactions were gastrointestinal symptoms including nausea/vomiting, anorexia, fatigue, alopecia and fever. Leukocytopenia and neutrocytopenia were also observed with a high incidence, but they recovered after 8 days from the nadir. The results show that docetaxel is an effective anti-tumor agent for advanced or recurrent gastric cancer. It is necessary to conduct another clinical trial by concomitant administration with other anti-tumor agents.

[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent gastric cancer: a Japanese Cooperative Study Group trial (group A)].

A late phase II clinical study of RP56976 (docetaxel) was conducted in patients with advanced/recurrent gastric cancer as a multicenter cooperative trial. Docetaxel was administered intravenously at a dose of 60 mg/m2 every 3-4 weeks. Of the 76 patients enrolled, 66 patients were eligible and 59 patients were evaluable for response. One patient showed complete response (CR), 13 patients partial response (PR), 1 patient minor response (MR), 19 patients no change (NC) and 25 patients had progressive disease (PD). The overall response rate in 59 evaluable patients was 23.7% (95% CI = 13.6-36.6%). The primary tumor showed a 4.3% (1/23) response, while the metastatic lesions in the abdomen, pelvic mass, lung, liver, and lymph nodes showed response rates of 62.5% (5/8), 33.3% (1/3), 33.3% (1/3), 14.8% (4/27), and 13.9% (5/26), respectively. About hematological toxicity, severe (Grade 3 or more) leukopenia was observed in 36 patients (56.3%) and neutropenia in 52 patients (81.3%). Other major toxicity (Grade 3 or more) included nausea/vomiting in 11 patients (17.2%), anorexia in 9 patients (14.1%), fatigue in 5 patients (7.8%), and alopecia in 7 patients (10.9%), all which were tolerable. The results show that docetaxel is an effective anticancer agent for advanced/recurrent gastric cancer.

[Clinical efficacy of GG032X tablets, a new dosage form of ondansetron (fast dispersing tablet), on cisplatin-induced nausea and emesis].

The inhibitory effects of GG032X tablets, a new dosage form (fast dispersing tablet) of ondansetron, 5-HT2 receptor antagonist, on nausea and emesis induced by cisplatin (CDDP), were investigated along with safety and usefulness. Subjects were chemotherapy patients starting CDDP administration for the first time, who were receiving a high single dose of CDDP (50 mg/m2 or more and intravenous drip infusion of less than 4 hours), or lower multiple doses of CDDP (a single dose of 10 mg/m2 or more, administered intravenously for 3-5 consecutive days). GG032X tablets were administered orally 1-2 hours before CDDP administration. In lower multiple doses of CDDP, GG032X tablets and CDDP were administered, as much as possible, at the same respective time when they were administered on the first day. Efficacy of GG032X tablets was evaluated in terms of inhibitory effect on nausea and emesis 24 hours after administration of a high single dose of CDDP, and of the inhibitory effect on nausea and emesis during the study period (3-5 days) in lower multiple doses of CDDP. Efficacy, safety and usefulness were evaluated in accordance with the evaluation criteria used in the clinical study of already-approved ondanstron tablets. In a high single dose of CDDP, the cases judged "effective" or better in the investigation of the inhibitory effect of the drug on nausea and emesis, accounted for 52.9% (63/119 cases). As for the overall safety rating, the cases judged as "safe" accounted for 87.0% (107/123 cases), and as a "minor safety problem" accounted for 13.0% (16/123 cases). As for the usefulness rating, the cases judged "useful" or better accounted for 52.1% (62/119 cases). Major adverse effects included headache, fever, atrial fibrillation and increases in total bilirubin, GOT and GPT values. None of these was serious, and the patients recovered without any treatment or by nosotropic therapy. Meanwhile, in lower multiple doses of CDDP, the inhibitory effect judged "effective" or better accounted for 70.6% (12/17 cases). As for the overall safety rating, all cases were judged "safe". In terms of usefulness, those cases judged "useful" or better accounted for 70.6% (12/17 cases). No adverse effect was observed. Study results of these two groups were almost the same as those for already-approved ondansetron tablets. According to the results of questionnaires for the patients who participated in the study and took GG032X tablets, the drug was found to be easy to take and had favorable results. Based on the above results, GG032X tablets were evaluated as having the same inhibitory effect as the already-approved ondansetron tablets against CDDP-induced nausea and emesis, and were considered safe and clinically useful.

[Quantitation of proteinuria by the use of protein-to-creatinine ratios in random urine samples].

Measurements of protein-to-creatinine ratios (Up/Cr) in simple voided urine samples were compared with 24-hour urinary protein excretions in order to quantify [correction of guantify] proteinuria in inpatients and outpatients. A highly significant linear correlation (r = 0.73), was observed between the two variables. A closer correlation was found in the urine samples obtained from outpatients with non-nephrotic syndrome and normal renal function. Furthermore, in the investigation of urine samples from inpatients, there was a significant correlation between the two variables in urine obtained during the morning, but neither in the early morning nor at night. However, there was no significant correlation between males and females. The results of our study indicate that Up/Cr in urine samples obtained during the morning provides an accurate quantitative estimate of protein excretion. Furthermore, in clinical practice, this is a suitable method of quantifying proteinuria in patients with renal diseases, particularly, non-nephrotic syndrome and normal renal function.

[Pharmacokinetic investigation of 5-day multiple dose of tropisetron capsule in patients who had received cisplatin and the usefulness of tropisetron capsule in the treatment of nausea and vomiting].

We have investigated the pharmacokinetics of a 5-day multiple oral dose of 5 mg tropisetron capsule in patients with malignant tumour who had received cisplatin single administration. Its anti-emetic effects on acute and delayed emesis and vomiting were also investigated. During the 5 days after this administration, changes in the release and metabolism of serotonin were investigated. The results may be summarized as follows: 1) The pharmacokinetic parameters of tropisetron revealed no significant change in the data between day 1 and day 5. Also, the parameters were almost similar to those observed in healthy adult males (clinical phase I study); Cmax. T1/2 and AUC 0-24 hrs on day 1 were 9.1 +/- 2.1 ng/ml, 12.5 +/- 4.2 hrs, 85.5 +/- 22.7 ng.hr/ml, respectively. The urinary excretion of the parent drug up until 24 hours after administration on day 1 was 3.8% of the dose administered and 2.9% of the total dose after the last administration; no difference in the urinary excretion rate was observed in healthy subjects. It was thus suggested that hydration accompanied by cisplatin administration did not affect the pharmacokinetics of tropisetron. 2) The changes in the amount of urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA) during 5 days after cisplatin administration were observed; urinary excretion of 5-HIAA increased 2.3 times (1.3-5.4 times) the baseline on the average during 6 to 12 hours on day 1. In 6 out of 10 patients, the increases in urinary excretion of 5-HIAA showed double or more the baseline during 2 to 5 days after cisplatin administration. Serotonin was thus deemed to be related to the development of delayed emesis. 3) The anti-emetic effects of tropisetron on acute and delayed emesis and vomiting were rated as "markedly effective" in 6 out of 11 patients (54.6%) and "effective" in 1 out of 11 patients (9.1%) on day 1; vomiting did not occur in any of these 7 patients. Tropisetron also controlled emesis and vomiting during days 2-5, and was rated as "almost favorable" in 6 out of 11 patients (54.5%). Further, in 4 out of 6 patients, in whom the urinary excretion of 5-HIAA was increased on day 2 onwards, vomiting did not occur during the time when the urinary excretion of 5-HIAA was increasing. On the basis of the above results, tropisetron is deemed to have certain antiemetic effects on delayed vomiting as well. Its 5-HT3 receptor mediated mechanism was similarly seen to inhibit acute nausea and vomiting.

[Clinical phase III study of tropisetron capsule in the treatment of nausea and vomiting induced by carboplatin or non-platinum anti-cancer drugs].

A clinical phase III study of tropisetron capsule was conducted to assess its efficacy, safety and usefulness on nausea and vomiting induced by carboplatin or non-platinum anti-cancer drugs. The study was conducted in patients who experienced vomiting on previous chemotherapy. Tropisetron 5 mg capsule was given to patients once 2 hours prior to the first administration of either carboplatin or non-platinum anti-cancer drugs; the patients were then observed for nausea and/or vomiting during 24 hours after the first administration. Some 56.7% (17/30) of the patients did not vomit after tropisetron administration, and the frequency of vomiting was significantly reduced compared with that during the previous chemotherapy. Further, in the clinical efficacy ratings, in which the efficacy was assessed on the basis of the nausea and vomiting data, 83.3% (25/30) of cases were rated as "effective or better". Adverse events observed were 3 cases of mild headache, but these were not clinically problematic. The above results reveal that tropisetron capsule is significantly effective and safe in the treatment of nausea and vomiting induced by carboplatin or non-platinum anti-cancer drugs; in addition, tropisetron proved to be highly useful for its convenience as an oral agent.

[Clinical phase III study of tropisetron capsule in the treatment of nausea and vomiting induced by anti-cancer drug; a placebo-controlled, multicenter, double-blind comparative study].

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.

[Clinical phase II study of tropisetron capsule in the treatment of nausea and vomiting induced by anti-cancer drugs].

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.

[Study of cardiac function in first stage examination of RA-700. RA-700 Clinical Study Group].

There are many studies in the literature on the subject of anti-neoplastic drugs for acute and chronic cardiac toxic function. It is important to check previously the cardiac toxicity of the new anti-neoplastic drugs. Now we have had a chance to study the first stage examination of RA-700, isolated from Rubia akane or Rubia cordifolia. Then we tried to study several kinds of parameters, for instance ECG, ultrasonic cardiograms and arterio-grams on cardiac toxicities of RA-700. We injected the first group of neoplastic patients only once with RA-700, while in the second group, we injected them with RA-700 for 5 consecutive days (see our previous report.) In the present study, we made some conclusions about the administration of RA-700. 1) Changes in cardiac function were noted in both groups. 2) Changes in blood pressure, sigma QRS, ejection fraction, and fractional shortening of the second group tended to be more extreme than those of the first group. Care for continuity is a concern with long-term and high doses of RA-700. 3) Because of the small sample, we could find no relationship between the changes in cardiac function and the injection doses of RA-700. 4) Therefore, the cardiac function must be checked by giving anti-neoplastic drugs to neoplastic patients.

[Clinical evaluation of granisetron for nausea and vomiting induced by anticancer drugs--optimal dose-finding study].

The efficacy, safety and usefulness of oral granisetron for nausea and vomiting induced by the administration of anticancer drugs were compared among four doses using the subjects registered through telephone calls by the physicians-in-charge. The clinical efficacy of the drug was assessed as "remarkably effective" or "effective" in 50.0% (11/22) in the 0.5 mg group. 68.4% (13/19) in the 1 mg group, 81.0% (17/21) in the 2 mg group and 78.3% (18/23) in the 4 mg group. The antiemetic effect of the drug persisted for approximately 24 hours in the 2 mg and 4 mg groups. No adverse event or abnormal laboratory value fluctuation which might pose a clinical problem was observed. From these results, single administration of oral granisetron at a dose of 2 mg once a day was considered to be the optimal administration and dosage for nausea and vomiting induced by the administration of anticancer drugs.

[Clinical evaluation of granisetron for nausea and vomiting induced by anticancer drugs--multi-centered placebo-controlled double-blind comparative study].

A placebo-controlled double-blind comparative trial was conducted to objectively assess the antiemetic effect on nausea and vomiting induced by anticancer drugs including cisplatin (CDDP) and safety of granisetron tablet (2 mg). In the present trial, single oral administration of the trial drug was performed one hour before the start of CDDP administration. 1) In clinical efficacy, the drug was assessed as "remarkably effective" or "effective" in 76.9% (30/39) in G group and 15.2% (7/46) in P group. The drug was assessed as "extremely useful" or "useful" in 84.6% (33/39) and 13.3% (6/45) in respective groups. These results indicated that G group was statistically significantly better than P group in these parameters. 2) In safety rating, the drug was assessed as "safe" in 100% (49/49) in G group and 95.9% (47/49) in P group, indicating equivalent levels between these groups. 3) The antiemetic effect of granisetron tablet was not dependent on patient's background factors including sex, P.S., the dose of CDDP and the number of anticancer drugs concomitantly used with CDDP. 4) The clinical effect of single oral administration of granisetron tablet (2 mg) persisted for approximately 24 hours. 5) In terms of the safety of the trial drug, there was no adverse event or abnormal laboratory fluctuation which might pose a clinical problem. From the above results, it was concluded that single oral administration of granisetron at a dose of 2 mg could suppress nausea and vomiting induced by the administration of anticancer drugs.

[Phase I Study of RA-700. RA-700 Clinical Study Group].

An antitumor substance, RA-700, isolated from Rubia akane or Rubia cordifolia has the novel structure. Phase I clinical study was conducted by the RA-700 clinical study group consisting of 6 institutions. A single dose administration and 5-day schedule administration were evaluated with 14 patients respectively. RA-700 was given from 0.2 to 1.4 mg/m2 in single i.v. dose study, from 0.4 to 2.0 mg/m2 in 5-day i.v. schedule study. Nausea and vomiting, fever, stomachache, mild hypotension and slight abnormality of electric-cardiogram were observed as the toxicities. In pharmacokinetic study, the elimination half-lives (t1/2) of RA-700 in plasma were 55 min, of alpha-phase and 3.9 hrs. of beta-phase by single dose study, and 23-25 min. of alpha-phase and 6-14 hrs. of beta-phase by 5-day schedule study. Accumulation was not found by 5-day schedule administration, and metabolite were not observed in plasma and urine. It seems that RA-700 is metabolized by the liver and excreted in the feces. In conclusion, the maximum tolerated dose was 1.4 mg/m2 for 5-day schedule administration.

[Anti-emetic effect and safety of single dose of ondansetron injection in double-blind comparison study with placebo].

In order to make an objective evaluation of anti-emetic effect, safety and usefulness of ondansetron injection in nausea and vomiting associated with cancer chemotherapy, we carried out a double-blind placebo controlled comparative study in patients receiving high-single dose (50 mg/m2 or more) of cisplatin. Either 4 mg of ondansetron or saline injection was given intravenously at 15 min. before administration of cisplatin. If anti-emetic effect of the test drug was insufficient, an additional dose of 4mg of ondansetron was given intravenously, as the rescue medication. Ondansetron was significantly superior to placebo in anti-emetic effect (p < 0.001). Efficacy rates were 66.7% (22/33 cases) in ondansetron and 20.0% (6/30 cases) in placebo groups. Seven and 21 cases required rescue medication with 4 mg single intravenous dose of ondansetron due to insufficiency of anti-emetic effect, in ondansetron group and placebo group, respectively. Thus the number of patients who required rescue medication was obviously greater in placebo group than that in ondansetron group. The rates of inhibitory effect of rescue medication on nausea and emesis were 14.3% (1/7 cases) in ondansetron group and 61.9% (13/21 cases) in placebo group. Side effects were observed in 1 case (eruption) in ondansetron group and in 2 cases (headache, diarrhoea; 1 case each) in placebo group. Furthermore, fever developed in 1 case in placebo group after the rescue medication. Elevation of total bilirubin value was observed in 2 cases in ondansetron group and 1 case in placebo group, however, these changes were mild and did not pose noteworthy clinical problem. From these results, ondansetron was shown to possess an excellent anti-emetic effect on nausea and emesis induced by highly emetogenic anti-cancer drugs, such as cisplatin, and to have no problem in safety, and thus it was considered to be a useful anti-emetic agent.

[Anti-emetic effect and safety of ondansetron tablet in double-blind comparison with placebo].

Ondansetron, a selective 5-HT3 receptor antagonist, has already been reported to have a marked effect to alleviate or prevent nausea and vomiting associated with cancer chemotherapy, after its intravenous administration. The present study was planned to examine the usefulness of its tablet form, which was prepared for the convenient use in outpatients receiving chemotherapy. In order to make an objective evaluation of anti-emetic effect and safety of ondansetron 4 mg tablet, this study was conducted in double-blind comparison versus placebo in patients receiving cisplatin at a single dose of 50mg/m2 or higher. Either 4 mg of ondansetron or placebo (lactose tablet) was administered orally once at 2 hrs prior to administration of cisplatin. If any satisfactory anti-emetic effects were not obtained, 4 mg of ondansetron injection was given once intravenously as a rescue medication. The inhibitory effect on nausea and vomiting was assessed in 4 grades as "excellent", "good", "fair" and "poor" based on severity of nausea and number of vomiting that occurred during the first 24hrs after administration of cisplatin. When rescue medication was conducted, the case was assessed as "poor". Ondansetron was significantly superior to placebo in inhibition of nausea and vomiting, in which efficacy rates (excellent+good) of ondansetron and placebo groups were 58.1% (25/43 cases) and 16.7% (7/42 cases), respectively. Number of cases requiring rescue medication with ondansetron injection was obviously greater in placebo group (31 cases) than that in ondansetron group (12 cases). In those patients given ondansetron injection as the rescue medication, satisfactory effects were obtained in 5 cases in ondansetron group and in 18 cases in placebo group. Although side effects including chest itching (ondansetron group), headache and dull headache (placebo group) were observed after the rescue medication with ondansetron injection, these symptoms were not severe and disappeared after 1-2 days. As mentioned above, ondansetron tablet was shown to possess excellent anti-emetic effect on nausea and emesis induced by high dose of cisplatin and to have no problem in safety. Hence ondansetron was proven to be clinically very useful anti-emetic.

[Evaluation of SN-307 (ondansetron), given intravenously in the treatment of nausea and vomiting caused by anticancer drugs including cisplatin--a placebo-controlled, double-blind comparative study].

Clinical usefulness of ondansetron as an antiemetic for the treatment of nausea and vomiting induced by anticancer drugs including cisplatin (> or = 50 mg/m2) was evaluated by a multi-institutional, double-blind comparative study with placebo with inpatients with various malignancies. In this study, efficacy, safety and usefulness of single dose of ondansetron (4 mg) or placebo (physiological saline), given intravenously for initial nausea and vomiting were observed for 24 hours after treatment. Clinically, very effective or effective response was seen in 64% (16/25) of the group O (ondansetron) and 5.9% (1/17) of the group P (placebo). No clinically significant adverse effects or abnormal laboratory test values were reported in the group of O. Diarrhea (1 case) and the elevation of laboratory test values (GOT.GPT, T-bilirubin, LDH, in 3 cases) were reported in the group of P. General safety assessment was considered "safe" in 100% of both group O and group P, and there was no statistical difference between two groups. Usefulness was considered as "useful" in 64% (16/25) of group O and 6.3% (1/16) of group P, and O was significantly better than group P (p < 0.001) level. In conclusion, ondansetron provides a safe and effective antiemetic measure when employed therapeutically against nausea and vomiting induced by regimens including cisplatin.

[Investigation of anti-emetic effect of ondansetron tablet in multiple doses on nausea and emesis associated with cisplatin].

The anti-emetic effects, safety and usefulness of ondansetron, a 5-HT3 receptor antagonist, given orally once daily for 3-5 consecutive days, were investigated in patients receiving a high single dose (greater than or equal to 50 mg/m2 or 75 mg/body) or lower multiple doses (greater than or equal to 15-20 mg/m2/day for 3-5 consecutive days) of cisplatin. Ondansetron 4 mg was administered orally once daily for 3-5 consecutive days. Efficacy rates in controlling nausea and emesis over the 3-5 days were 77.3% (17/22 cases) and 66.7% (6/9 cases) in patients receiving a high single dose and lower multiple doses of cisplatin, respectively. Side effects were observed in 2 cases (headache and elevation of blood pressure in one case and only headache in the other case.). Abnormality in clinical laboratory findings was observed in 1 case. From the above, ondansetron, showing high efficacy by oral administration 4 mg once daily for 3-5 consecutive days, without any problem in safety, was considered to be a useful anti-emetic agent.

[Examination of inhibitory effect, safety and usefulness of SN-307 (ondansetron) administered orally once daily for 3-5 consecutive days on nausea and emesis associated with non-platinum anti-cancer drugs].

We examined the anti-emetic effect, safety and usefulness of ondansetron hydrochloride, a selective 5-HT3 receptor antagonist, given orally once daily at the dosage of 4 mg, for 3 to 5 consecutive days to patients with nausea and emesis induced by non-platinum anti-cancer drugs such as cyclophosphamide, doxorubicin and carboplatin. Out of 84 cases where anti-emetic effects were evaluated, numbers of cases assessed as excellent and good were 36 (83.3%) and 34 (40.5%), respectively, the efficacy rate being 83.3% (70/84). Side effects, such as moderate constipation (3 cases) and mild headache (3 cases), were observed in 8/85 cases (9.4%). Abnormalities in clinical laboratory findings including elevation of hepatic function and uricacid values and increase in eosinocyte counts, were observed in 3/85 cases (3.5%). As to overall safety, 78/85 cases (91.8%) were evaluated as having no problem in safety, and 7/85 cases (8.2%), as having minor problem in safety. As to clinical usefulness based on anti-emetic effect and overall safety, out of 79 cases the drug was assessed as very useful in 29 cases (36.7%) and useful in 35 cases (44.3%), the rate of "useful" or above being 81.0% (64/79). Furthermore, when ondansetron was administered in 3 courses of chemotherapy, though the number of patients was small, it was shown that anti-emetic effect of ondansetron did not decline and no problem in safety was observed. From the above, ondansetron which exerted adequate anti-emetic effect in 4 mg once daily doses was considered as a useful and safe anti-emetic in treatment of nausea and emesis associated with cancer chemotherapy.

[Evaluation of SN-307 (ondansetron), given intravenously for the treatment of nausea and vomiting caused by anticancer drugs including cisplatin-open study].

The anti-emetic effect, safety and clinical usefulness of ondansetron for the treatment of nausea and vomiting caused by anticancer drugs including cisplatin, was evaluated by a multi-institutional study in patients with various malignancies. In this study, ondansetron was given intravenously with mainly a single dose of 4 mg to intervene nausea and vomiting. 1. Efficacy ratio of overall effects on nausea and emesis observed for 24 hours after treatment was 69.8%. 2. No side effect was observed. Laboratory tests showed temporary elevation of serum uric acid level in 1 patient in the group given 4 mg. 3. From these results, it seems that ondansetron, given intravenously after initial vomiting, was highly safe and clinically useful anti-emetic for the treatment of nausea and vomiting associated with anti-cancer drugs.

[Clinical evaluation of ondansetron (injection of a single intravenous dose) against nausea and emesis associated with anti-cancer drugs--dose-finding study in patients receiving cisplatin].

We examined anti-emetic effects, safety and the optimal dose of Ondansetron Injection given in a single intravenous dose in patients receiving a single high dose of cisplatin in randomized controlled comparative study using telephone registration. Ondansetron was injected intravenously in a single dose of 4 mg, 8 mg or 12 mg, at 15 minutes before administration of cisplatin. Nausea and emesis were observed for 24 hours after administration of cisplatin. Efficacy rate of inhibitory effects on nausea and emesis were 76% (19/25 cases) in the 4 mg dose group, 57% (12/21 cases) in the 8 mg dose group and 83% (20/24 cases) in the 12 mg dose group, without a statistically significant difference among 3 dose groups. Hence, it was estimated that the low dose of 4 mg was adequate to exert satisfactory anti-emetic effects. No clear relationship between onset time of the initial emetic episode and plasma concentrations of Ondansetron was found in 16 cases of the 4 mg dose group, 11 cases in the 8 mg dose group and 15 cases in the 12 mg dose group. Side effects observed during this study period were headache and diarrhea in 1 case in the 12 mg dose group. Both symptoms were mild and resolved without treatment. No abnormal findings attributable to Ondansetron were observed in clinical laboratory test. From the above, it was considered that Ondansetron given by a single intravenous injection was highly effective to inhibit nausea and emesis induced by cisplatin, and was highly safe. As to the dose, 4 mg once daily was considered to be adequate for prophylaxis of cisplatin-induced nausea and emesis.

[Anti-emetic effect and safety of consecutive use of ondansetron injection in cisplatin-induced nausea and emesis].

Anti-emetic effect, safety and clinical usefulness of Ondansetron injection given in the dose of 4 mg once daily by intravenous administration for 3-5 consecutive days were examined in patients receiving a high single dose (not less than 50 mg/m2 or over 75 mg/body) and lower multiple doses (over 15-20 mg/m2 once daily, for 3-5 consecutive days) of cisplatin. Efficacy rates of inhibitory effects on nausea and emesis in patients receiving the high single dose of cisplatin were 76% on the 1st day, 67% on the 2nd day and 78% on the 3rd day, the average being 71% (86/121 cases) for the 3 days. Those in patients receiving lower multiple doses of cisplatin were 83% on the 1st day, 78% on the 2nd day, 61% on the 3rd day, 65% on the 4th day and 57% on the 5th day, the average being 72% (13/18 cases) for the 3-5 days. Side effects were observed in 15 cases out of 207 (1st course, 182 cases; 2nd course, 21 cases; 3rd course, 4 cases), and major symptoms were headache and fever. Also, abnormalities in clinical laboratory findings attributable to Ondansetron were observed in 13 cases, mainly consisting of elevation of the hepatic function values. From the above, Ondansetron injection which showed sufficient anti-emetic effects on acute emesis and delayed emesis induced by a high single dose or lower multiple doses of cisplatin with its once daily intravenous dose given for 3-5 consecutive days, were considered a safe and clinically useful anti-emetic.