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Biomedical subjects

I Nakao

Publications and source records attributed to I Nakao.

At least 55 records · Page 3Linked to original sources

[Phase I study of 5'-deoxy-5-fluorouridine (5'-DFUR)].

A phase I study of a new fluorinated pyrimidine compound, 5'-deoxy-5-fluorouridine (5'-DFUR), was performed in 37 patients with various malignant cancers. Starting dose was 600 mg/m2/day (900 mg/body/day) and escalated up to 3900 mg/body/day. The dose given was divided into 3 administrations a day for 5 consecutive days. Subjective symptoms were observed in cases given a dose of over 2,100 mg/body/day. Gastro-intestinal disturbances such as nausea, vomiting and anorexia were the major side effects. In the hematological and urinary examinations, no severe abnormal signs were observed. The maximum tolerated dose was considered to be 2.100 mg/body/day, and the dose-limiting factor was gastro-intestinal disturbance. 5-FU levels were determined in the serum and tumor tissues. 5'-DFUR was well absorbed. The 5-FU level in tumor tissue was very high at 2 to 3 hours post-dose and then rapidly decreased, being 0.05 microgram/g 12 hours after administration. The optimal dosage for a phase II study was suggested to be less than 2,100 mg/body/day.

Administration, Oral↗

[Phase II study of 5'-deoxy-5-fluorouridine (5'-DFUR) in patients with malignant cancer--a multi-institutional cooperative study].

A phase II study of oral 5'-deoxy-5-fluorouridine (5'-DFUR) was conducted on a multi-institutional basis. Six hundred and ninety-two cases were entered into this study and evaluated by the extramural review committee. In 437 evaluable cases the response rate was 16.0%, 13 CR and 57 PR. The response rate of gastric cancer was 14.3%, 1 CR and 19 PR out of 140 evaluable cases, that of colorectal cancer was 9.2%, 1 CR and 6 PR out of 76 evaluable cases, and that of breast cancer was 35.9%, 11 CR and 26 PR out of 103 evaluable cases. The response rate was high with a long-lasting efficacy in breast cancer. Although the number of cases was small, PR was observed in 3 cases of head & neck, and in 1 case each of esophagus, gall-bladder and thyroid cancer. The optimal daily dosage was considered to be 800-1,200 mg/body/day. The tumor began to decrease in size within 8 weeks of treatment in most of the responded cases. Side effects were observed in 44.4% of 513 cases. Diarrhea occurred with the highest rate (26.3%), but this was controllable.

Anorexia↗

[Clinical evaluation of schizophyllan (SPG) in advanced gastric cancer (the second report)--a randomized controlled study].

We reported previously that Schizophyllan (SPG) combined with MMC + 5-FU (MF regimen) or Tegafur (F regimen) had a significant life-prolonging effect over chemotherapeutic regimens in patients with inoperable and recurrent gastric cancer in a randomized controlled study. In the present paper, we have further investigated the effect of SPG on life-span followed-up for more than 2 years. A significant life-prolonging effect of SPG was reconfirmed in patients given either the MF regimen (154 patients) or the F regimen (213 patients). Thus, SPG combined with chemotherapeutics has proved to be useful for treating patients with inoperable and recurrent gastric cancer, resulting in a significant prolongation of life-span without serious side effects despite having no influence on tumor size.

Antineoplastic Combined Chemotherapy Protocols↗

[Phase II study of KW 2083 [7-N-(p-hydroxyphenyl)-mitomycin C] in patients with various cancers].

A phase II study of KW 2083 [7-N-(p-Hydroxyphenyl)-Mitomycin C] was carried out in 14 cases of stomach cancer, 5 of lung cancer, 5 of colon cancer and 5 other types of cancer. KW 2083 was intravenously injected at a dose of 40 mg/body weekly in 26 cases. Among 23 evaluable cases, partial response was obtained in 6 cases (26%). The PR cases were 4 of stomach cancer and 2 of lung cancer, the former being all undifferentiated adenocarcinoma. Regarding hematologic toxicities, thrombocytopenia was the most principal toxicity and an important weak point of KW 2083. Thrombocytopenia (less than 75,000/mm3) was observed in 13 cases (50%). Recovery took about 4 weeks, but by that time 3 cases had still not recovered to 75,000/mm3. leukocytopenia (less than 3,000/mm3) was observed in 17 cases (65%). Concerning gastrointestinal symptoms, anorexia occurred in 11 cases (42%), nausea and vomiting in 11 cases (42%), diarrhea in 1 case and stomatitis in 1 case. T1/2 (beta-phase) of KW 2083 was half that of Mitomycin C.

Adolescent↗

[Experience in combination therapy with amikacin and cephapirin for infections complicated with acute leukemia during induction chemotherapy].

We treated infections accompanied with induction chemotherapy in 9 patients with acute leukemia by the combination of amikacin (AMK) and cephapirin (CEPR). The result was that 1 case was markedly effective, 2 cases were effective, 3 cases were marginally effective, 2 cases showed no effect and 1 case who underwent prophylactic medication had no infection. We recognized no adverse effects by AMK or CEPR. We concluded that the combination of AMK and CEPR was useful as first choice to the treatment of infections during induction chemotherapy of acute leukemia.

Acute Disease↗

[A tentative of guideline for phase III study and its problems in clinical aspect].

A draft of guideline for phase III study of anticancer drugs was presented, and its objective problems in practical aspect was discussed. The anticipated of phase III study is to evaluate the clinical usefulness of anticancer drug in terms of effectiveness and toxicity. And the comparative study of new drugs with standard therapy is most important. The comparative study includes two trials: randomized controlled trial and the second non-randomized controlled trial. Considering the precision of study, the randomized controlled trial is most rational, but it includes some controversies in practical use and ethical aspect. On the other hand, non-randomized controlled trial includes some problems on comparability in relation to prognostic factors.

Antineoplastic Agents↗

[Clinical evaluation of schizophyllan (SPG) in advanced gastric cancer--a randomized comparative study by an envelope method].

To clarify the clinical efficacy of SPG, a beta-1, 3 glucan extracted from cultured Schizophyllum commune Fries, a randomized comparative study was performed in combination with mitomycin C+5-fluorouracil (MF protocol) or tegafur (F protocol). A total of 514 cases with inoperable or recurrent gastric cancer were randomly allocated to either the SPG group or the control group, 367 of which were finally assessed for clinical efficacy. SPG was intramuscularly given at a dose of 20 mg twice a week or 40 mg once a week. Significant prolongation of life span was confirmed in the SPG group (MF protocol: p less than 0.01, F protocol: p less than 0.05), although the combination of SPG did not demonstrate a remarkable antitumor effect in both MF and F protocols. Among immune response parameters tested, the positive reactions in the PHA skin test were maintained in the SPG group and decreases in lymphocyte counts were inhibited by SPG in the MF protocol. Side effects associated with SPG therapy were noted in 6 of 258 cases treated with SPG. From these results, it is indicated that the combination of SPG and the chemotherapeutic agents may be useful in treating patients with inoperable or recurrent gastric cancer.

Adjuvants, Immunologic↗

[Phase II study with methyl-6[[[2-chloroethyl) nitrosoamino] carbonyl] amino]-6-deoxy-alpha-D-glucopyranoside (MCNU) in hematological malignancies].

A total of 117 cases with hematological malignancies were treated with MCNU at doses of 70-100 mg/m2. Following are the results obtained. 1. MCNU showed a marked depression of cells in the cases with CML, polycythemia vera and thrombocythemia. The low level of cells was maintained for 2 to 7 months. 2. A good response was observed in several cases with blastic crises of CML. 3. No response was observed in two cases with acute leukemia. 4. Although a fair response was observed in several cases with malignant lymphoma or multiple myeloma, moderate bone marrow suppression was observed in a majority of the cases.

Adult↗

[Conditions suitable for chemotherapy of gastric cancer].

In order to investigate the applicable conditions to gastric cancer chemotherapy, we analyzed the various prognostic factors from the aspect of gastric cancer patients and anticancer drugs. 148 out of a total of 188 cases were evaluated in which PR was observed in 25 cases (16.9%). The man 50% survival time of all patients was 4.2 months, and the one-year survival was found in 14 cases (8.2%). The important prognostic factors were performance status, classification of metastases site and the efficacy of chemotherapy. From this results, it is thought that the best applicable conditions to gastric cancer chemotherapy were that a sufficient dose of multidrugs should be administered to the patients with less advanced cancer or good ps patients.

Antineoplastic Combined Chemotherapy Protocols↗

[Electrolyte metabolism and emergency].

In outlining the pathology of various electrolyte metabolism abnormalities in cancer patients we considered the main clinical points between pathologies and emergency treatment. In regard to sodium (Na+) metabolism, one pathologic state that requires our attention is hypernatremia. Hypernatremia is accompanied with dehydration and is due to water loss, vomiting, diarrhea and renal insufficiency. One of the major causes of this condition is lack of the antidiuretic hormone due to intracranial metastasis of the tumor. When hypernatremia becomes severe, it is accompanied with circulatory failure, muscular asthenia, disorientation, convulsions, coma and other cerebral symptoms. Treatment consists of replenishing the water content by infusion of electrolyte solutions which should be carefully conducted after complete diagnose of the severity of the patient's pathological condition. Hyponatremia, like sick cell syndrome, is observed relatively frequently in cancer patients. When the serum Na level falls markedly, it induces cerebral edema and causes disorders of consciousness. The major treatment consists of providing both water and sodium supplements. Hyperkalemia is observed at the time of renal insufficiency, tissue lesions, vomiting, and diarrhea. When serum potassium level rises, it causes bradycardia, ventricular fibrillation, or cardiac arrest. It is important to diagnostically apprehend the severity of this condition using EKG and determining the serum K1+ level. For emergency treatment injection of calcium gluconate is very effective. Hypokalemia is often manifested by the loss of intestinal fluids due to diarrhea or during administration of diuretic agents. Clinical symptoms include neural paralysis but emergencies occur relatively infrequently. K C1 injections are used in treating this condition. Hypercalcemia is manifested in cancer patients during hyperparathyroidism. Its clinical symptoms include lassitude, tachycardia, nausea, vomiting, and renal dys-function, leading to neural symptoms in severe cases. The main treatment consists of injection of physiological saline solution and administration of calcitonin, mithramycin. Hypocalemia is manifested during renal insufficiency, lack of vitamin D, and hypothyroidism. In classic cases it causes tetanic spasms. Injection of calcium is an effective treatment but since during tetanic spasms alcalosis may easily occur, treatment should only be provided after obtaining a complete understanding of the patient's condition. The pathological conditions described above can not be said to specific to cancer but it should be kept in mind that one of their main causative factors is the involvement of mechanism which produces ectopic hormones from cancerous tissues.

Emergencies↗

[Phase I study of a new anticancer agent CAM--results of cooperative study].

CAM is a derivative compound of mycophenolic acid produced by Penicillium brevicompactum, and is a new oral Purine antagonistic anticancer agent. The Phase I study was carried out cooperatively in ten hospitals. The results are as follows: The administration method was single administration and the starting dose was 200 mg/m2 (1n). The dose level was escalated according to varied Fibonacci formula. The number of total cases was thirty-one: three cases at 1n level, four at 2n, six at 3.3n, six at 7n and seven at 9n. Side effects were observed in five of thirteen cases over 7n dose levels, such as nausea, vomiting, anorexia and diarrhea. Leukopenia was developed in only one case at 7n dose level. Other side effects such as anemia, thrombocytopenia, and disturbances of liver function and renal function were not observed. It was estimated from above results that a dose limiting factor of CAM is nausea and vomiting. A subtoxic dose was 7n (1,400 mg/m2) and a maximum tolerated dose was 9n (1,800 mg/m2) which corresponded to 2,200-3,000 mg as a single administration.

Animals↗

Multidrug combination in cancer chemotherapy: MFU therapy.

Three-drug therapy with Mitomycin-C (MMC), 5-fluorouracil (5-FU), and a nitrosourea derivative, ACNU, was carried out in 72 cases of carcinoma patients, mostly of stomach carcinoma. 1) According to Karnofsky's criteria, an effect of above I-A was observed in 10 of 35 cases (29%) treated with MFU-I (0.08 mg/kg of MMC, 10 mg/kg of 5-FU and 0.4-0.8 mg/kg of ACNU twice a week for the first two weeks and once a week thereafter for a total of six weeks as one course), 5 of 14 cases (36%) with MFU-I-O (MFU-I plus 0.2-2.0 KE of OK-432 i.m. three times a week), and 6 of 20 cases (30%) with MFU-II (0.2 mg/kg of MMC once in two weeks, 5 mg/kg of 5-FU every day, 2 mg/kg of ACNU once in six weeks as one course). 2) According to the criteria of the group of Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare, a partial response was seen in 29% of the cases treated with MFU-I, in 38% of the cases treated with MFU-I-O, and 30% of the cases treated with MFU-II. 3) Side effect was slight in the digestive organs but the bone marrow suppression was remarkable. Leukopenia and thrombocytopenia were seen in the majority of patients under treatment. The hematological side effect appeared early in MFU-II therapy, but it was not severe and recovered quickly. Combined use of OK-432 seemed to be effective to shorten the period of hematological disorders. Thus, three-drug combination treatment with MMC, 5-FU, and ACNU seems to be useful for patients with malignant tumor, chiefly of the digestive organs. Especially, MFU-II treatment schedule seems to be a combination therapy that has relatively small hematological side effects.

Drug Therapy, Combination↗

Clinical experiences with aclacinomycin-A.

Aclacinomycin is a new anthracycline analog of adriamycin and daunomycin. Aclacinomycin contains three sugars. The drug has been studied in 22 cases in a phase 1 type of trial on a schedule 20 mg i.v. every other day up to a total of 300 mg. Toxicity has consisted of myelosuppression, nausea and vomiting, and transient hepatic disturbances. Evidence of clinical activity was observed in several cases including a case of breast cancer and gastric cancer. Although no full patial remissions were recorded, further study is continuing.

Animals↗