A phase 3, randomized, double-blind study of single-dose fosaprepitant for prevention of cisplatin-induced nausea and vomiting: results of an Indian population subanalysis.

CONTEXT: Currently, there is limited data on the prevention of chemotherapy-induced nausea and vomiting (CINV) in Indian patients. AIMS: This post hoc study assessed the efficacy and safety of fosaprepitant compared with aprepitant for prevention of CINV in the Indian population. A subgroup analysis was performed from data collected in a phase 3 study of intravenous (IV) fosaprepitant or oral aprepitant, plus the 5-HT 3 antagonist ondansetron and the corticosteroid dexamethasone, in cisplatin-naοve patients with solid malignancies. MATERIALS AND METHODS: Patients scheduled to receive cisplatin (≥70 mg/m 2 ) were administered a single IV dose of fosaprepitant dimeglumine (150 mg) on day 1 or a 3-day dosing regimen of oral aprepitant (day 1:125 mg, days 2 and 3:80 mg) with standard doses of ondansetron and dexamethasone. Patients recorded nausea and/or vomiting episodes and their use of rescue medication and were monitored for adverse events (AEs) and tolerability. STATISTICAL ANALYSIS USED: Differences in response rates between fosaprepitant and aprepitant were calculated using the Miettinen and Nurminen method. RESULTS: In the Indian subpopulation (n = 372), efficacy was similar for patients in both the fosaprepitant or aprepitant groups; complete response in the overall, acute, and delayed phases and no vomiting in all phases were approximately 4 percentage points higher in the fosaprepitant group compared with the aprepitant group. Fosaprepitant was generally well-tolerated; common AEs were similar to oral aprepitant. CONCLUSIONS: IV fosaprepitant is as safe and effective as oral aprepitant in the Indian subpopulation and offers an alternative to the oral formulation.

Cerebral venous thrombosis in pregnancy and puerperium--a prospective study.

During a prospective study of cerebrovascular accidents we evaluated 64 cases of cerebral venous thrombosis (CVT) in pregnancy and puerperium. CVT made up approximately half of the young strokes and 40% of strokes occurring in females. Majority of them were below 25 years of age, multipara women from rural areas who were delivered at home by untrained dais. While 79.6% cases occurred during first two weeks after delivery, the incidence of antepartum CVT was also higher at 7.8%. Majority of the patients had meningoencephalitic (70.32%) presentation. Others in the spectrum had either acute fulminant type (18.7%), neuropsychiatric (6.25%) or pseudotumour cerebri like presentation (4.68%). Patients with neuropsychiatric and pseudotumour cerebri like presentation had a better prognosis while those with acute fulminant type had a poorer outcome. The patients with bilateral hemorrhagic infarcts and diffuse cerebral edema on CT scan had a poorer prognosis. A lower mortality rate (18.75%) could be achieved with early diagnosis and quick institution of planned therapy.

[Effective administration of recombinant granulocyte colony-stimulating factor to prevent granulocytopenia due to combination chemotherapy for testicular germ cell tumors].

A prospective randomized study on the administration of recombinant granulocyte colony stimulating factor (rG-CSF) was conducted on 15 patients with testicular germ cell tumors. The clinical stagings of all patients except one were minimal to moderate extent according to the Indiana University staging system. Combination chemotherapy using bleomycin, etoposide and cisplatinum (BEP) was performed as the initial treatment on the eligible patients. rG-CSF was administered by two different methods; 1) routine administration on the 6th day after BEP chemotherapy (group A), and 2) the same method, but after granulocytopenia of 1,500/mm3 had developed (group B). The administration of rG-CSF in group A significantly reduced the severity of leucocytopenia and also the incidence of stomatitis compared with group B. Although rG-CSF produced no significant side effects, the thrombocytopenia was prominent in the group A patients (not significant). BEP chemotherapy itself is an easily-tolerable and well established method for treating young adult patients. The method used in group B seems to be suitable in situations where thrombocytopenia and cost effectiveness.

Opposite effects of interleukin-4 and interleukin-10 on nitric oxide production in murine macrophages.

Interleukin-4 (IL-4) and interleukin-10 (IL-10) were evaluated for their ability to inhibit the production of nitric oxide (NO) by interferon-gamma (IFN-gamma)- or lipopolysaccharide (LPS)-activated murine macrophages (RAW 264.7 and J774.2). Macrophages pre-treated with IL-4 and then stimulated with IFN-gamma or LPS showed significant inhibition in their ability to produce NO as measured by nitrite production. Simultaneous treatment of IL-4 pre-incubated cells with IFN-gamma and LPS together augmented nitrite accumulation. On the other hand, similar exposures of the macrophages to IL-10 followed by IFN-gamma or LPS treatments resulted in significantly increased NO production. Thus IL-10 failed to suppress IFN-gamma or LPS-induced NO production and showed opposite effects in these experiments to IL-4. We conclude that the two lymphokines have differing roles in the control of production of NO and might act to control the secretion of nitric oxide in vivo.

Primary reading epilepsy : a case report.

We report a case of primary reading epilepsy in a 14 years female.

[Clinicopathological evaluation of etoposide or estramustine phosphate in castrated patients with advanced prostatic cancer].

BACKGROUND: We conducted a multicentric randomized trial to compare bilateral orchiectomy versus bilateral orchiectomy plus etoposide or estramustine phosphate as first-line therapy for advanced prostatic cancer (stage D2). METHODS: From January 1991 to December 1992 a total of 46 newly diagnosed cases (registered cases) of advanced (stage D2) prostatic cancer was randomized into 3 groups as follows; Group A: bilateral orchiectomy and 25 mg/day of etoposide every 2 weeks for 6 months. Group B: bilateral orchiectomy and 560 mg/day of estramustine phosphate for 6 months. Group C: bilateral orchiectomy alone. One of group A and one of group B were ineligible cases, so 44 were eligible. In the eligible cases, ages were ranged from 54 to 90 (mean of 71.2) years old. No significant difference of patients' characteristics was found among 3 groups and median follow-up period was 25 months. Response was evaluated based on the response criteria according to Japanese urological association. Specifically, a central pathologist who blinded to the treatment was employed for evaluating pathological response at six months. RESULTS: Of the 44 eligible patients, 33 and 25 were evaluated for clinically and pathological analyses, respectively. Clinical response rates were 80% (12/15) of group A, 100% (4/4) of group B and 78.6% (11/14) of group C. No significant difference in the clinical response and survival rate was shown among the three groups. Significantly higher frequencies of side effects were noted in the grop B compared to the other two groups (p < 0.05) and cardiovascular complications were the most frequent in group B. Favorable pathological response was obtained in all of group B, but not statistically significant compared with 7/21 (33.3%) of response rate in group A and C. The pathological response was significantly correlated with the clinical one in all patients (p < 0.01). While 8 of 11 patients (73%) with pathological response grade 1, 2 and 3 achieved clinical PR (partial response) or CR (complete response), only 5 of 14 (36%) with grade 0 received PR or CR. CONCLUSIONS: We conclude that low dose administration of etoposide or estramustine phosphate dose not improve clinical response and survival in a short term in castrated patients, but increases the adverse effects due to the drugs in these patients. In addition, the pathological evaluation at 6 months after treatment appears to reflect the clinical response at that time in newly diagnosed patients with advanced prostatic cancer.

Prophylactic chemotherapy with anthracyclines (adriamycin, epirubicin, and pirarubicin) for primary superficial bladder cancer. The Hokkaido University Bladder Cancer Collaborative Group.

A multicentric randomized trial was conducted to evaluate the efficacy of intravesical chemoprophylaxis for primary superficial bladder cancer. The 299 eligible patients with primary superficial bladder cancer were randomized into four groups (A, B, C, and D) after pathological confirmation. Intravesical instillation of drugs, which were dissolved in 20 ml physiological saline (PS; group A, 20 mg Adriamycin; group B, 20 mg epirubicin; group C, 20 mg pirarubicin; group D (control), PS alone], was performed once a week for 2 weeks after trasurethral resection and then once every 2 weeks for 14 weeks, once monthly for 8 months, and once every 3 months for 1 year. No significant difference in the patients' characteristics was found among the four groups. The follow-up period ranged from 3 to 31 months (mean, 14 months). The nonrecurrence rates were estimated by the method of Kaplan and Meier. The relative effects of five variables (the tumor status, size, grade, and stage and the treatment) on the efficacy of the chemoprophylaxis regimens were evaluated using a multiple regression model. Although the nonrecurrence rates determined for groups A and B were significantly higher than that found for group D (P < 0.05), no significant difference in the nonrecurrence rate was detected among groups A, B, and C. The multiple regression model indicated that the most important factors in preventing tumor recurrence at 12 or 24 months were the intravesical instillation of an anthracycline and the tumor status (solitary). These results demonstrate that intravesical instillation of the tested anthracyclines is effective for at least 2 years as prophylactic chemotherapy for primary superficial bladder cancer.

Prophylactic chemotherapy for primary and recurrent superficial bladder cancer: preliminary results. The Hokkaido University Bladder Cancer Collaborating Group.

A multicenter trial for postoperative prophylaxis of the recurrence of superficial Ta-T1, G1-G2 bladder cancer was performed. Eligible patients with primary or recurrent superficial bladder cancer were randomized into four groups. For the primary cases, intravesical instillation of drugs [group A, 20 mg Adriamycin (ADM) + 200 mg cytosine arabinoside (CA) in 30 ml physiological saline; group B, 10 mg peplomycin (PEP) + 200 mg CA in 30 ml physiological saline; group C, 2 mg neocarzinostatin (NCS) + 200 mg CA in 30 ml physiological saline; and group D, control] was carried out once a week for 2 weeks, once every 2 weeks for 14 weeks, once monthly for 8 months, and, finally, once every 3 months for 1 year. For the recurrent cases, intravesical instillation of 20 mg ADM + 200 mg CA in 30 ml physiological saline as described above and daily oral administration of another drug [group E, 300 mg/day UFT; group F, 200 mg 5-fluorouracil (5-FU)/day; group G, 30 mg ubenimex/day; and group H, no oral drug] was performed. The postoperative follow-up period was 3-36 months. A total of 193 primary cases and 121 recurrent cases of superficial bladder cancer were evaluated. The cumulative 12-month nonrecurrence rates for the primary cases were 86.2% in group A, 78.1% in group B, 82.1% in group C, and 68.4% in group D. The cumulative nonrecurrence rate obtained using ADM+CA (group A) was significantly higher than the control value. On the other hand, no significant difference was found in the cumulative nonrecurrence rates calculated for the recurrent cases, regardless of the oral drug given. Intravesical instillation of ADM+CA for primary superficial bladder cancer was considered to be useful, but the long-term effect of intravesical instillation remains to be elucidated. Further refinement of this regimen is necessary for effective prophylaxis of the recurrence of superficial bladder cancer.

Evaluation of systemic chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin for advanced bladder cancer. The Japanese Urological Cancer Research Group for Adriamycin.

In a cooperative study of the Japanese Urological Cancer Research Group for Adriamycin, the usefulness of chemotherapy with methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC therapy) in treating advanced or recurrent bladder cancer was examined. Evaluation of the clinical responses obtained in 86 evaluable patients revealed 13 complete responses, 29 partial responses, 4 minor responses, 19 cases of no change, and 21 cases of progressive disease. The overall response rate was 48.8% (42/86). The rate of response to M-VAC therapy at each disease site was as low as 21.4% (3/14) in bone lesions but exceeded 40% in the primary lesion, the lymph nodes, the lung, the liver, and other lesions. The clinical response to M-VAC therapy was not significantly influenced by the performance status of the patients, the dose intensity, or previous therapy. The median duration of response for the 42 responders was 22.7 weeks (range, 8.1-134.1 weeks), and the median duration of survival for the 86 evaluable patients was 9.8 months. Side effects were frequently encountered; the patients experienced anorexia, nausea, vomiting, malaise, alopecia, and leukopenia, but all of these symptoms were tolerable.

[A clinical study of associated bladder cancer in patients with renal pelvic and ureteral cancer].

We reviewed 76 cases of renal pelvic and ureteral cancer, admitted to our hospital between January, 1975 and December, 1988, with special reference to the occurrence of bladder cancer. Bladder cancer was associated with an upper urinary tract neoplasm in 35 of the 76 cases (46.1%), 7 with a preceding bladder cancer, 17 with a coexistent one and 11 with a subsequent one. In case of renal pelvic and upper ureteral cancer the incidence of coexistent or subsequent tumors of the bladder was 28.7% (16 of 56 patients). However, in the cases of lower ureteral cancer the incidence of these tumors was 82.4% (14 of 17 patients). This incidence was significantly higher than that in renal pelvic and upper ureteral cancer. The subsequent bladder cancer was observed in 19 patients including 8 patients who had a recurrence of the bladder cancer after the treatment for a preceding and coexistent bladder cancer. The cancer in most cases occurred within 2 years after the treatment of the upper urinary tract neoplasm. Of 19 patients who had subsequent bladder cancer 11 had primary sites in the renal pelvis and upper ureter. Another 8 patient had primary sites in the lower ureter. Four of the 8 subsequent bladder cancers in patients with lower ureteral cancer occurred just on and around the affected ureteral orifice. All these 4 tumors were high grade and high stage tumors. On the other hand, another 15 patients developed subsequent bladder cancer in a place other than the affected ureteral orifice. Of these 15 patients, 13 cases showed a low grade and low stage tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical evaluation of bunazosin hydrochloride for the treatment of voiding disturbances due to neurogenic bladder--a double-blind study].

The therapeutic utility of bunazosin hydrochloride was evaluated by a multi-center (67 hospitals) double-blind controlled study in patients who complained of voiding disturbances due to neurogenic bladder. For means of comparison, bethanechol chloride and placebo were used as reference drugs. Bunazosin hydrochloride was orally administered 1.5 mg per day for the first week and 3.0 mg per day for two weeks thereafter (Group E). Bethanechol chloride 15 mg (Group B) and placebo (Group P) were orally administered three times daily for three weeks. Three hundred and twenty-three cases were subjected to this study. The global improvement rating was analyzed for 244 cases (83 in Group E, 78 in Group B and 83 in Group P). The global utility rating (GUR) was analyzed for 252 cases (84 in Group E, 81 in Group B and 87 in Group P). Three hundred and twenty cases (107 in Group E, 104 in Group B and 109 in Group P) were analyzed with respect to overall safety rating (OSR). The global improvement ratings (excellent and good) were 32.5% in Group E, 28.2% in Group B and 21.2% in Group P. In the evaluation of GUR, Group E was superior to Group P. In addition, the incidence judged to be useless in Group E was significantly lower than that in Group B. There were no differences in OSR among these three groups. In the total evaluation of the subjective symptoms, the rates of improvement were not different among these three groups. In the total evaluation of the objective findings, the improvement rate in Group E was significantly higher than that in Group P. In addition, the deterioration rate in Group E was significantly lower than that in Group B. In objective findings before and after administration of bunazosin hydrochloride (Group E), the volume of residual urine, the rate of residual urine and the average flow rate improved significantly However, the bladder capacity, the maximum resting bladder pressure and the maximum urethral pressure did not change significantly. Bunazosin hydrochloride improved the objective findings regardless of the bladder capacity and the maximum resting bladder pressure. These significant improvements were marked in the neurogenic bladder patients who were able to urinate and in the patients whose urethral pressure was high. There were no differences in the incidence of side effects or in the appearance of abnormal values of laboratory findings in these three groups. Neither specific signs nor serious clinical side effects except those reported previously were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

[A double-blind trial on the effect of bunazosin hydrochloride for the symptoms of benign prostatic hypertrophy].

A multicenter clinical trial was carried out on 372 patients in double-blind conditions in order to determine the clinical effects of Ea-0643 (bunazosin hydrochloride) on voiding disorders in benign prostatic hypertrophy, compared with paraprost and placebo. Of the 372 patients, 129 were assigned to bunazosin hydrochloride, 118 to paraprost and 125 to placebo. The improvement rating for all five subjective symptoms improved with passage of time in all the bunazosin hydrochloride, paraprost and placebo groups. A higher improvement rating was obtained in the bunazosin hydrochloride group for retarded urination, urinary stream condition and abdominal pressure at voiding, while the improvement rating was higher for prolonged urination in the placebo group and for residual urine in the paraprost group, but there was no significant difference in improvement ratings between the groups. The daily frequency of voiding decreased to a significant extent in the bunazosin hydrochloride and placebo group at week 1, and there was a significant difference between the bunazosin hydrochloride and the paraprost groups and between the placebo and the paraprost groups. The improvement rating for conditions of voiding was higher with the bunazosin hydrochloride group, when "slightly or better improved" cases were taken into account, but there was no difference between the groups. As for objective symptoms, maximum and average flow rate, useful measures for clinical evaluation of drug effects on voiding disorders, were significantly increased, with a decrease to match in residual urine ratio in the bunazosin hydrochloride group. In terms of maximum and average flow rate bunazosin hydrochloride was significantly superior to paraprost at weeks 1 and 2 and superior to placebo at weeks 2 and 4 and at the final evaluation as well. In terms of residual urine ratio bunazosin hydrochloride was superior to both paraprost and placebo. The global improvement rating, as assessed by the U- and chi 2-tests, was significantly higher in the bunazosin hydrochloride group than in the paraprost group, and there was a significant difference in global improvement ratings, as assessed by the chi 2-test, between the placebo and the paraprost groups, when "moderately or better improved" cases were taken into account. The stratified analysis of the prostate glands, subjective symptoms, maximum flow rate and residual urine ratio revealed that in patients with more advanced conditions the bunazosin hydrochloride group showed significantly superior improvement rates than the paraprost and placebo groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Benign fibrous histiocytoma of the kidney.

A case of benign fibrous histiocytoma of the kidney in a 48-year-old man is reported. A 7-year followup has revealed no recurrence. To our knowledge there have been no previous reports of benign fibrous histiocytoma of the kidney.

[Clinical significance of multiple biopsies of nontumorous bladder mucosa in patients with bladder cancer].

Multiple biopsy specimens obtained from nontumorous bladder mucosa were investigated histologically. An average of 3.6 specimens was taken in 142 transurethral resection operations for 112 patients with bladder cancer. The histological categories used were normal epithelium, metaplasia, hyperplasia and G1-G3 dysplasia. Thirty-seven patients (27.7%) had G2 less than dysplasia within normal looking bladder mucosa. In patients with high grade bladder cancer, the incidence of the association with dysplasia was 51.7%, which was significantly higher than the rates in patients with low or moderate grade bladder cancer (p less than 0.05). The tumor recurrence was observed in 45 patients of 102 patients who were followed with bladder preservation. The recurrence was seen in 13 of 19 patients (68.4%) with mucosal dysplasia in the previous operation. The rate was significantly higher than 38.6% in patients without dysplasia (p less than 0.05). Thus, the epithelial dysplasia seen in nontumorous bladder mucosa were associated with higher grade bladder tumors more often, and the histology of multiple biopsy specimens might be one of predictors for tumor recurrence in near future.

[Clinical experience of enoxacin complicated urinary tract infection].

Enoxacin (ENX) was administered to 69 patients with complicated urinary tract infections (UTI). Clinical efficacy and safety were evaluated by the criteria proposed by the UTI Committee, Japan. The overall clinical efficacy was excellent in 60.9%, moderate in 10.1% and poor in 29% of the patients. Of the 76 strains isolated from the patients 61 strains (80.3%) were eradicated. Subjective side effect was observed in one patient who complained of slight nausea. No drug-related aggravation in the laboratory test was observed. These results showed that ENX was effective and safety for the treatment of complicated urinary tract infection.

Postoperative reduction of serum beta-HCG in testicular seminoma.

Serum beta-HCG and urinary HCG were measured in 17 patients with histologically proved pure seminoma of the testis. The patients have been followed to date for 10 to 74 months after orchiectomy, and have no residual disease or recurrence of their disease. Preoperative urinary HCG levels were abnormal in 9 patients (53%). Serum beta-HCG levels were slightly elevated in 6 out of 12 patients evaluated, and were reduced after orchiectomy even in patients with preoperative normal beta-HCG levels (P less than 0.05). Preoperative levels of the tumour marker in seminoma were far lower than in patients with non-seminomatous germ cell tumours, but it would not be rare to see a small amount of HCG produced by the tumour cells in the seminoma.

Papillary adenoma of the bladder in a patient with intermittent self-catheterization.

We report a case of papillary adenoma of the bladder. The patient had had intermittent self-catheterization for the previous 3 years. The tumors developed multiply and were identified on the trigone and posterior wall of the bladder. Dysplasia of the urothelium was associated in nontumorous areas. Transurethral resection of the tumors was performed. The tumor recurred 3 times for 3 years, but no malignant changes were identified.

[Clinical evaluation of combination therapy with Fortimicin and Cefotax in the treatment of complicated urinary tract infections].

Clinical efficacy of combination therapy using Fortimicin (ASTM) and Cefotax (CTX) was studied in 63 patients with complicated urinary tract infections. The patients received 200 mg of ASTM i.m. and 1 g of CTX i.v. twice a day. The overall clinical efficacy of the treatment was evaluated by criteria proposed by the Japanese UTI Committee. The overall clinical efficacy rate was 68.3%. The rate was 67.3% in the patients with single bacterial infection and 72.7% in those with mixed infections. Subjective side effects were observed in one of the patients. Drug related aggravation in laboratory tests was observed in 8 items in 8 patients, but these were mild changes. We concluded that combination therapy with ASTM and CTX was useful for the treatment of complicated urinary tract infections.