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H Niitani

Publications and source records attributed to H Niitani.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Early phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer. ETP 21 Study Group--Cervical-Ovarian Cancer Group].

We conducted multi-site early phase II trial or oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer in cooperation with 19 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Cycles were repeated every 28 days. In cervical cancer, 24 patients were enrolled and 17 of them were evaluated. The overall response rate including CR and PR was 23.5% (4/17). In ovarian cancer, 18 patients out of 21 enrolled were evaluated. The overall response rate was 16.7% (3/18). The primary toxicity observed was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were anorexia, nausea, vomitting, fatigue, alopecia and stomatitis. From these results we concluded that oral etoposide administered for 21 consecutive days was effective against cervical cancer.

Administration, Oral↗
PubMed1998

[Phase I study of raltitrexed (ZD-1694)].

A multicenter cooperative phase I study of ZD-1694 (raltitrexed), a novel, folate-based thymidylate synthase (TS) inhibitor, was conducted with single and repeated doses in 30 patients with various malignant tumors. ZD-1694 was intravenously infused over 15 minutes. In the single-dose study, the initial dose was fixed at 1.0 mg/m2 (1n), and the dose was escalated stepwise up to 3.5 mg/m2 (3.5 n). Based on the results of the single-dose study, in the repeated-dose study, doses of 2.5 n and 3 n were infused every three weeks (3 weeks/one course). In principle, patients received 2 courses or more. Of the 29 eligible patients, 16 were in the single-dose study and 13 in the repeated-dose study. Adverse reactions were evaluated in all eligible patients. In the single-dose study, neutropenia, nausea/vomiting, diarrhea, and transaminase (GOT, GPT) increases, of grade 3 or higher, occurred at high doses of 3 n and 3.5 n. These were regarded as dose-limiting toxicities (DLT). DLT of grade 3 or higher were observed in 1 of 4 patients given 3 n and 2 of 4 patients given 3.5 n. These results suggested that the maximum tolerated dose (MTD) of ZD-1694 was 3.5 n (3.5 mg/m2). In the repeated-dose study, DLT of grade 3 or higher was observed in no more than one third of each dose group, 2 of the 6 patients given 2.5 n and 2 of the 7 patients given 3 n. These results suggested that 3 n (3.0 mg/m2), a dose nearer to MTD, was the recommended dose for the phase II study. Although transaminase increases were observed in all patients, in 12 of them the increase was grade 2 or lower and reversible. A pharmacokinetic investigation showed the mean elimination half life of ZD-1694 plasma concentration was 91.5 hours in the single-dose group and 119.1 hours in the repeated dose group. It was suggested that ZD-1694 is metabolized to polyglutamates after uptake and retained in the cells for a long duration. However, no accumulation was seen in plasma concentration of ZD-1694 following repeated doses at 3-weekly intervals. One PR was observed in a patient with colorectal cancer receiving 2.5 n in the repeated-dose study. Based on these results, the recommended dosage and administration for the phase II study of ZD-1694 was 3 n (3.0 mg/m2) intravenously infused over 15 minutes every 3 weeks.

Adult↗
PubMed1997

Activity of gemcitabine in the treatment of patients with non-small cell lung cancer: a multicenter phase II study.

Gemcitabine is a novel nucleoside analog with unique activity against a wide range of solid tumors. We initiated a multicenter phase II study in patients with non-small cell lung cancer (NSCLC) to evaluate the efficacy and safety of gemcitabine. Eligible patients had stage III and IV, previously untreated with chemotherapy, age range from 18 to 80 years, and ECOG performance status 0 2. Gemcitabine was administered at 1000 mg/m2 as a continuous i.v. infusion once a week for a consecutive 3 week period, followed by 1 week of rest. Of the 69 patients enrolled, 67 patients were eligible for efficacy evaluation. The overall response rate was 20.9% with a 95% confidence interval of 11.9-32.6%. The median survival time was 9.0 months and the 12 month survival rate was 31.3%. Grade 3 or 4 toxicities included neutropenia in 22.7%, anemia in 13.4%, leukopenia in 10.4%, anorexia in 10.4%, malaise in 7.5% and nausea/vomiting in 6.0%. Serious toxicities were septic shock and interstitial pneumonia (one patient each). Gemcitabine, administered weekly for three consecutive weeks followed by 1 week of rest, is an active agent for NSCLC. Gemcitabine is currently being evaluated in combination with cisplatin and other agents.

Adult↗
PubMed1997

[Lymphocytic interstitial pneumonia associated with Sjögren's syndrome and mediastinal lymphadenopathy: diagnosis by open-lung biopsy].

A 56-year-old woman was admitted to the hospital because of dry coughing and shortness of breath on exertion. In addition, dry eyes and cornea guttata suggested Sjögren's syndrome. Chest radiography revealed linear, reticular shadows throughout the lung fields, and enlargement of hilar and mediastinal lymph nodes. A specimen was obtained by transbronchial lung biopsy but the findings were not condusive; open-lung biopsy was done. The histopathological findings suggested lymphocytic meterstitial pneumonia. Results of genetic analysis and of immuno-histochemical examination conformed that the proliferating lymphocytes were polyclonal. Corticosteroids and immunosuppressive drugs have been used to treat lymphocytic interstitial pneumonia, and they were effective in this case.

Biopsy↗
PubMed1997

Phase II studies of gemcitabine for non-small cell lung cancer in Japan.

To determine the activity and toxicity of gemcitabine (2',2'-difluorodeoxycytidine), three phase II single-agent studies have been conducted in patients with non-small cell lung cancer in Japan. In an early phase II study, 17 previously treated and 47 untreated patients were treated with gemcitabine. Gemcitabine was given intravenously at a dose of 800 mg/m2 or 1,000 mg/m2 once a week for 3 weeks followed by a week of rest, repeating every 4 weeks. Although none of the patients with prior therapy responded, eight (17%) of 47 previously untreated patients showed a partial response. Toxicities of grade 3 or greater included leukopenia (12.5%), thrombocytopenia (6.3%), and anemia (15.6%). We entered 73 patients (group A) and 67 patients (group B) into two late phase II studies. All patients had no previous chemotherapy and had measurable disease. Gemcitabine was administered at a starting dose of 1,000 mg/m2/wk for 3 weeks followed by a week of rest. The dose was escalated to 1,250 mg/m2 if severe toxicity was not seen in the previous course. Nineteen of 73 patients (26%) had a partial response (95% confidence interval, 16.5% to 37.6%) in group A. Of 67 patients, 14 (20.9%) showed a partial response (95% confidence interval, 11.9% to 32.6%) in group B. Grade 3 or greater anemia and leukopenia occurred, respectively, in 15 (20.5%) and seven (9.6%) patients in group A and in nine (13.4%) and seven (10.4%) patients in group B. Grade 3 thrombocytopenia was observed in one patient (1.4%). Other toxicities including hepatic toxicity, fatigue, nausea/vomiting, and fever were mild and transient. Pulmonary toxicity was observed in five patients, two of whom died of respiratory insufficiency. The median durations of response were 19.6 weeks in group A and 20 weeks in group B, and median survival times were 44 and 39 weeks, respectively. In conclusion, gemcitabine is an active agent against non-small cell lung cancer with very mild toxicities. These results suggest that gemcitabine has potential utility on an outpatient basis. Further trials in combination with other active agents are warranted.

Adult↗
PubMed1997

[TUT-7 phase I clinical study. TUT-7 Study Group].

A phase I study with TUT-7, a new anthracycline antitumor antibiotic, was conducted in 35 malignant tumor patients at 11 institutions nationwide. The study was initiated with a single dose at 100 mg/body which was equivalent to 2n, then the dose as escalated up to 700 mg/body in accordance with the modified Fibonacci's scheme. The dose limiting factor (DLF) was considered to be leukopenia, and maximum tolerated dose (MTD) was 700 mg/ body. The consecutive days dosing study subsequently conducted started with 25 mg/body/day, and the dose level was escalated up to 150 mg /body/day. TUT-7 was orally administered for seven (7) to fourteen (14) consecutive days in principle. It was considered that DLF was leukopenia and MTD was 100 mg/body/day for consecutive days dosing. The study indicated that serum drug concentrations reached their plateaus on the 5th day after initiation of TUT-7 treatment and the accumulation of this compound was low. With these findings, a regimen with a dose of 100 mg/body/day orally administered for 14 consecutive days was recommended for early phase II studies.

Administration, Oral↗
PubMed1997

[TUT-7 early phase II clinical study for various solid tumors and hematologic malignancies].

An early Phase II study with TUT-7 (menogaril), a new anthracycline antitumor antibiotic, was conducted in patients with various malignant tumors at 81 departments of 65 institutions nationwide. One course of TUT-7 treatment consisted of seven (7) or fourteen (14) consecutive days of administration at 75 or 100 mg/body/day with two-week drug withdrawal; at least two courses of treatment were given in principle. Among the 165 patients registered, 145 patients were eligible and 128 patients were evaluable for antitumor efficacy. In 11 patients with malignant lymphoma, one (1) had CR and five (5) had PR (54.5%); in three (3) patients with prostate cancer, one (1) had PR (33.3%); and in 12 patients with uterine cervical cancer, two (2) had PR (16.7%). Adverse drug reactions frequently observed were digestive organ disorders (anorexia and nausea/vomiting) and malaise. The abnormality in laboratory tests observed frequently was myelosuppression (leukopenia and neutropenia).

Adult↗
PubMed1997

UFT plus cisplatin in advanced non-small-cell lung cancer: interim analysis of 67 patients.

A single-institution phase II study indicated that combination chemotherapy using UFT (tegafur and uracil) plus cisplatin (Platinol) in patients with non-small-cell lung cancer was active with less host toxicity than other cisplatin-based therapies. To confirm these observations, the Japan JFT Lung Cancer Study Group conducted a multi-institutional phase II trial. The number of patients planned for this trial is 110. Eligibility includes previously untreated stage IIIB or IV non-small-cell lung cancer and a good performance status. UFT 400 mg/m2 in two divided doses is administered orally on days 1 through 14, and cisplatin 80 mg/m2 is injected IV on day 8. This treatment is repeated every 3 or 4 weeks. Between April 1995 and May 1996, 67 patients were enrolled, and all 67 were considered eligible for an interim analysis performed in October 1996. Among 63 patients evaluable for response, there was an overall response rate of 30% (95% confidence interval, 19% to 41%), with one complete response and 18 partial responses. With a median follow-up duration of 44 weeks, the median survival time was 32 weeks and the 1-year survival rate was 25%. Grade 3 leukopenia occurred in only 1 of 67 patients (1.5%), and there was no thrombocytopenia of grade 3 or greater. Vomiting, the most common nonhematologic toxicity observed, reached grade 3 or 4 in only 6 patients (9%). This interim analysis seems to support the observations of the previous single-institution phase II trial.

Aged↗
PubMed1997

[Phase I study of S-1. S-1 Study Group].

We have conducted Phase I study of a novel oral antitumor agent of fluorinated pyrimidines, S-1, in which tegafur (FT) is combined with two classes of modulator, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) at a molar ratio of FT:CDHP:Oxo = 1:0.4:1 as a multi-center study with 16 institutions nationwide. Two administration methods, once and twice daily administrations, were evaluated. As a result, MAD was determined as 150 mg/body/day approximately 200 mg/body/day and 75 mg/body x2/day approximately 100 mg/body x2/day, respectively. DLF was myelosuppression, mainly consisting of leukopenia in the two administrations. Most adverse reactions observed, including myelosuppression, disappeared by discontinuation of administration, and recovery was in about 2 weeks. Adverse reactions other than myelosuppression which induced the discontinuation were rash and vomiting. Other adverse reactions observed were anorexia, malaise, diarrhea and stomatitis. Diarrhea and stomatitis were mild (Grade 1), except those observed at a dose of 200 mg/body/day, and did not induce discontinuation of administration. Based on these findings and pharmacokinetic evaluation, the recommended dose and administration for Early Phase II studies were determined as twice daily administration of 75 mg/body for 28 consecutive days with 14 days rest (1 course).

Administration, Oral↗
PubMed1996

Stability of p53 tumor suppressor gene mutations during the process of metastasis and during chemotherapy.

We analyzed 29 pairs of primary and metastatic lung carcinomas obtained at autopsy for mutations in the p53 gene, using the polymerase chain reaction-single strand conformation polymorphism method (PCR-SSCP). We examined the relationship between p53 gene mutations and the development of metastasis, and the stability of p53 gene mutations during chemotherapy. The tumors consisted of six small cell carcinomas, 13 adenocarcinomas, eight squamous cell carcinomas, one large cell carcinoma, and one adeno-squamous cell carcinoma. PCR-SSCP analysis showed that three small cell carcinomas (50%), three adenocarcinomas (23%), two squamous cell carcinomas (25%), and one large cell carcinoma (100%) had p53 gene mutations. All these abnormalities were found between exon five and exon eight. The mutations in the primary tumors and the metastatic tumors were identical. These results suggest that p53 gene mutations occur before distant metastases develop, and that they may be stable during the process of metastasis. There were nine metastatic tumor samples that existed before the patients received chemotherapy. These samples showed identical p53 mutations as the corresponding primary tumor. This suggests that anticancer drugs rarely induce p53 gene mutations.

Base Sequence↗
PubMed1996

Randomized study of vinorelbine (VRB) versus vindesine (VDS) in previously untreated stage IIIB or IV non-small-cell lung cancer (NSCLC). The Japan Vinorelbine Lung Cancer Cooperative Study Group.

PURPOSE: We compared the activity of vinorelbine (VRB) and vindesine (VDS) in a randomized crossover study in patients with previously untreated stages IIIB or IV non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Two hundred four patients were assessable for response and toxicity. VRB was administered at a dose of 25 mg/m2 weekly and VDS at a dose of 3 mg/m2 weekly. Patients who failed to respond after 4 cycles of initial monotherapy were switched to a combination chemotherapy (VRB-->VDS + cisplatin (P) or VDS-->VRB + P). RESULTS: Objective response was observed in 31.1% of patients in the VRB arm versus 8.9% of those in the VDS arm (P = 0.0002). The median duration of response to VRB was 18.5+ weeks (range, 7.9 to 107.5+ weeks) compared with 11.7+ weeks (range, 6.0 to 35.0+ weeks) for VDS. Of the 69 patients who failed to respond to initial monotherapy, 33 in the VRB group who subsequently received VDS + P did not respond and 13 (26.5%) of 49 initially on VDS who received subsequent VRB + P responded. The rates of grades 3 and 4 leukopenia were similar in the two monotherapy arms (VRB, 55.3% vs. VDS, 48.5%). However, grade 3 anemia was more frequent in the patients on VRB than in those on VDS. The incidence of peripheral neurotoxicity was significantly higher with VDS than with VRB (P = 0.002), but VRB induced a slightly higher rate of local cutaneous reaction than VDS (P = 0.012). With the combination of cisplatin and these vinca alkaloids, peripheral neurotoxicity was less frequent in the VRB group than in the VDS group. CONCLUSION: Our results demonstrate that VRB yields a higher response rate than VDS in stage IIIB or IV NSCLC, with the same extent of toxicity in terms of leukocytopenia. The peripheral neurotoxic effects were also milder with VRB than with VDS. In second-line chemotherapy, there was a notable difference in response between the VRB + P and VDS + P regimens.

Adult↗
PubMed1996

Phase II trial of docetaxel in previously untreated advanced non-small-cell lung cancer: a Japanese cooperative study.

PURPOSE: This phase II study was conducted to evaluate the efficacy and toxicity of moderate-dose (60 mg/m2) docetaxel in Japanese patients with previously untreated advanced (stage IIIB or IV) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Docetaxel 60 mg/m2 was administered intravenously over 1 to 2 hours to patients with previously untreated stage IIIB or IV NSCLC. Treatment was repeated every 3 weeks. No routine premedication was given. The patients' median age was 67 years (range, 40 to 80). Forty-four patients (59%) had adenocarcinoma and 55 (73%) had stage IV disease. The median Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 1. RESULTS: Seventy-five patients were eligible and treated with docetaxel. Fourteen patients (19%) achieved a partial response (PR); response was not significantly affected by histology or clinical stage. The median survival time for all patients was 297 days. The predominant toxicity was neutropenia, with 87% of patients experiencing grade 3 or 4. Febrile neutropenia was seen in eight patients. Hypersensitivity and edema each occurred in only 4% of patients and were easily manageable. There was no possible treatment-related death of acute exacerbation of pneumonitis. CONCLUSION: Docetaxel 60 mg/m2 showed significant activity in advanced NSCLC, with a low incidence of hypersensitivity or peripheral edema. Further investigation of this agent in NSCLC is warranted, especially in combination with other active drugs.

Adenocarcinoma↗
PubMed1996

[Early phase II study of BMS-181339 (paclitaxel) in patients with non-small cell lung cancer. BMS-181339 Non-Small Cell Lung Cancer Study Group].

We conducted a multi-institutional (11 facilities), early phase II study of BMS-181339 (paclitaxel), a novel anti-cancer drug, for non-small cell lung cancer (NSCLC). The 150 mg/m2 dose of paclitaxel was given by intravenous infusion over 24 hours every three weeks. When fifteen patients were accumulated, the interim review revealed that three of 15 eligible patients had a partial response for a response rate of 20%. The most common toxic effects were grade 3 or 4 leukopenia seen in 73.3% (11/15), and grade 4 neutropenia in 93.3% (14/15). One patient with neutropenia had suspected septic shock, which could be managed by G-CSF and antibiotics. No serious hypersensitivity reaction was seen with premedication of anti-allergic drugs, although mild allergic reactions such as skin rash and flush, were observed in 20.0% (3/15). Other adverse reactions, including alopecia, fever, arthralgia, myalgia and peripheral neuropathy, were mild in most cases. We conclude that it is relevant to proceed to a late phase II study for NSCLC.

Adult↗
PubMed1996

[The development of a new QOL Questionnaire on chemotherapy - induced emesis and vomiting--investigation of reliability and validity. Group for Investigation of QOL Questionnaire for Anti-Emetics Used in Cancer Chemotherapy. Joint Research Group for Tropisetron Double-Blind Comparative study].

A new questionnaire on QOL of patients with chemotherapy-induced emesis and vomiting was developed, and its reliability and validity were investigated in the present multi-center clinical trial. The questionnaire consisted of 15 items which included descriptive questions on appetite, feeling, sleep, mental fatigue, anxiety, pain, sputum, respiratory distress, nausea, vomiting, abdominal condition, daily life in a hospital and relationship with family, a linear analogue scale representing influence of nausea and vomiting on patient's life during 24 hours, and a face scale as the global scale. Data from 98 patients with cancer were analyzed by principal component analysis and correlation analysis. The results were summarized as follows: 1) Recollect rate was 78.1% and complete response rate was 86.0% in this QOL measurement. 2) A clear correlation was observed between appetite, feeling, nausea, vomiting and the physiological scale, between sleep, mental fatigue, anxiety, pain, abdominal condition and the psychological scale, between sputum, respiratory distress and the respiratory condition related scale, between daily life in hospital and the active scale, between relationship with family and the social relation scale. These results satisfied internal consistency. 3) As for test-retest reliability, the total score of 13 descriptive items between the day before and two days before the start of chemotherapy showed no significant difference. 4) The 13 items were grouped into physiological, the psychological, the respiratory condition related, the active and the social relation scales, and these scales belonged to a different dimension. 5) The linear analogue scale, the face scale and the total scores of 13 descriptive items correlated respectively with all of items except item of, relationship with family. 6) As for concurrent validity, vomiting frequency, severity of nausea and anorexia correlated with the physiological scale. Severity of nausea and anorexia also correlated with the psychological and active scales. 7) As a result of investigation of sensitivity, the total score of the 13 descriptive items, the linear analogue scale representing influence of nausea and vomiting on patient's life during 24 hours and the face scale revealed the poorest levels 2-3 days after chemotherapy but recovered thereafter. The aggravation of QOL of patients treated with chemotherapy was reduced in the anti-emetic administration group compared with the placebo administration group. These results suggested that this new questionnaire developed for chemotherapy-induced emesis and vomiting had sufficient validity and reliability to reflect the effects of anti-emetic drug.

Aged↗
PubMed1996

[Effects of an anti-emetic tropisetron capsule on QOL of patients with delayed nausea and vomiting induced by cancer chemotherapy. Group for Investigation of QOL Questionnaire for Anti-Emetics used in Cancer Chemotherapy. Joint Research Group for Tropisetron Double-Blind Comparative Study].

We have reported our "new questionnaire of QOL (quality of life) in anti-emetic therapies during cancer chemotherapy" and demonstrated its reliability and validity. In the present study we investigated the utility of tropisetron capsules for delayed nausea and vomiting induced by cancer chemotherapies with CDDP single administration in a placebo-controlled double-blind comparative study using the questionnaire. The questionnaire was composed of the following scales: a physiological scale (appetite, feeling, vomiting, nausea), a psychological scale (sleep, mental fatigue, anxiety, pain, abdominal condition), a respiratory condition related scale (sputum, respiratory distress), an active scale (daily life in a hospital), a social relation scale (understanding of the family), a linear analogue scale for evaluation of the influence of nausea and vomiting in patient's life during 24 hours, and a face scale as the global scale. First, all patients were administered a preventive dose of tropisetron capsule on day 1 (the day of CDDP administration) and then allotted to once-daily oral administration of either a tropisetron (T group) or a placebo (P group) capsule during days 2 to 5 by a double-blind method. Chronological changes of QOL during the study period were measured by the area under the curve (AUC) generally used for calculation of blood levels of drugs. The maximum fluctuation (Difmax) of QOL scores throughout the whole study period was also evaluated. The data were collected from 114 cases, and 98 cases (51 in P group, 47 in T group) were analyzed. 1) The total score or 13 items (a modified linear analogue scale with 5 graduations), the face scale and linear analogue scale of T group were higher (better) than those of P group. 2) As for the total score of each scale, the physiological, psychological and active scales in the T group showed higher (better) levels than the P group. 3) As for the AUC values, the T group was lower (better) than the P group in most items. In AUC of the total score of 13 items, the face scale, the physiological and the psychological scales, the T group was significantly superior to the P group. 4) AUC levels of each item belonged to the physiological and the psychological scales in the T group tended to be lower (better) than the P group, and "sleep" and "pain" in the psychological scale were significantly lower (better) in T group than P group. 5) In Difmax values, all scales except respiratory condition related scale showed lower levels (better) in T group and the total score of 13 items, the face scale and the physiological and psychological scales showed significantly lower levels than P group. 6) Difmax values in each item belonging to the physiological and psychological scales showed lower levels in the T group, while "appetite" and "vomiting" in the physiological scale and "sleep" in the psychological scale showed significantly lower levels (better) than those of the P group. 7) In the stratified analysis performed for patients without nausea and vomiting on the 1st day of chemotherapy, there was no significance in AUC levels of all items in both groups. In patients with nausea and vomiting on the 1st day, the total score of 13 items, the face scale, the physiological and the psychological scales in the T group were significantly better than in the P group. 8) It was suggested that the anti-emetic efficacy of tropisetron for delayed nausea and vomiting might reduce the undesirable influence of chemotherapy on QOL, especially on the physiological and the psychological effects. These results suggested that this new questionnaire is applicable for evaluation of the utility of anti-emetics in patients in cancer chemotherapy, and that tropisetron capsules could reduce the decrease of QOL in delayed nausea and vomiting induced by chemotherapy.

Adolescent↗
PubMed1996

[LY188011 phase I study. Research Group of Gemcitabine (LY188011)].

LY188011 (Gemcitabine hydrochloride) is a new derivative of deoxycytidine. Phase I study was carried out by a cooperative study group. LY188011 was administered weekly for 3 consecutive weeks starting with an initial dose of 60 mg/m2 (1n) and then increasing the dosage to 1,000 mg/m2 (16.7n). Dose limiting factor was found to be myelosuppression (decreases of WBC, neutrophils and platelet), and MTD was considered to be 1,000 mg/m2. The nadir of WBC and platelet were observed after about 1-3 weeks. It took 1-2 weeks for their recovery. Other adverse reactions included fever, fatigue, anorexia, nausea/vomiting, anemia and transient elevations of GOT and GPT. However, those adverse reactions were mild. T1/2 rho of plasma concentration was about 19 min and the C5min was dependent on the dose. Anti-cancer effects were observed in one gastric cancer and two colon cancer patients. It is recommended that the dosing schedule for an early phase II study is 800 mg/m2 weekly for 3 weeks with 1 week of rest as one cycle, in multiple cycles.

Adult↗
PubMed1996

[Phase I study of bicalutamide (Casodex), a nonsteroidal antiandrogen in patients with prostatic cancer].

A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.

Administration, Oral↗