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Biomedical subjects

H Majima

Publications and source records attributed to H Majima.

At least 73 records · Page 4Linked to original sources
PubMed1984

[Phase I clinical study].

The main purpose of the phase I clinical study is to define the tolerable doses in each various administration schedules depend upon by careful clinical observations and by pharmaco-kinetic, -dynamic studies. final goal of the phase I clinical study is to establish the safe, most reasonable administration schedules to perform further clinical studies, including phase II, III and possibly iv. In addition, it is quite reasonable to observe efficacy of the given agent if possible. The patients who are selected to receive the phase I clinical study should be fulfilled the followings: (1) Histological proof of malignancy; (2) No best available therapy regimen at present; (3) Maintain reasonably well organ functions which are suitable to observe side reactions (4) No hang-over reactions from previous therapy and; (5) Consent from patient himself or members of the family concerning the study. The set-up of the initial administration dose should be established from mouse and dog preclinical studies. Retrospective studies revealed reasonably safe and efficient to start from the most sensitive dose in 1/5 LD10 of mouse or 1/5 TDL of dog on the mg square meter basis. Above method is widely used at present and it is a potential replacement for the large animal species as a routine procedure. Dose escalation routinely proceeded using a double dose escalation procedure or modified Fibonacci procedures with minimal risk. It is permitted to escalate administration dose in the same patient under careful considerations. The new agent which has enough reliable clinical date in the abroad, the clinical study in this country would be simplified. The phase I clinical study should be performed in the well-equipped institutions under the supervision of capable investigators. The guide line of phase I clinical study would be revised whenever it is necessary.

Antineoplastic Agents↗
PubMed1983

[Cerebrospinal fluid distributions of systemically administered fluorinated pyrimidines].

Transfer of systemically administered fluorinated pyrimidines (Tegafur, TAC-278, HCFU and FD-1) to cerebrospinal fluid was studied in 7 patients primary brain tumors. Seven patients had had irradiation and also had V-P shunt operation for hydrocephalus 5-FU concentration in CSF was extremely high in FD-1 and TAC-278 administration, but not in Tegafur and HCFU administration. In addition, Tegafur and HCFU did not reveal any cumulative effects of 5-FU in CSF by continuous prolonged systemic administration. The facts suggest strongly the usefullness of the agents in the treatment of intracranial neoplasms, which have high CSF concentrations. However, intermediate metabolites of 5-FU in CSF are different from those in systemic pathway, and FD-1 and TAC-278 produce CNS toxicities. Therefore, further extensive studies are necessary to utilize these agents for the treatment of intracranial neoplasms.

Adult↗
PubMed1983

Kinetics of thermotolerance decay in Chinese hamster ovary cells.

The kinetics of thermotolerance decay and cell proliferation was determined following initial heat treatments of 10 or 30 min at 44 degrees in Chinese hamster ovary cells. Thermotolerance was more pronounced following the longer initial heat treatment, but maximal tolerance developed by 10 hr in both cases. After its maximal development, tolerance decayed in an exponential manner. The half-times of tolerance decay were 11 or 16 hr following 10- or 30-min pretreatments. Thermotolerance was apparent in the progeny of heated cells for 4 to 5 postheat cell generations.

Animals↗
PubMed1983

[Preliminary phase II clinical study of 4'-O-tetrahydropyranyl doxorubicin (THP-ADM)].

THP-ADM is a new antitumor antibiotic which belongs to the anthracycline group. This agent was administered to 42 histology proven various malignant disease patients with a schedule of 60-80 mg per body (40-55 mg per m2) iv bolus, every three weeks. THP-ADM administration revealed mild upper GI toxicity (vomiting 19%, stomatitis 21%) and leukopenia (less than 2,000 per mm3) in 80% and thrombocytopenia (less than 60,000 per mm3) in 38% with good rebound. There was no signs or symptoms of cardiac failure including the patient who had received 740 mg per body (500 mg per m2). Definite response (CR, PR) was observed in ovarian carcinoma 4/11, cervix carcinoma 2/7, breast carcinoma 1/6, malignant lymphoma 5/5 and mesothelioma 1/2. Furthermore, some response (MR) was observed in lung metastasis from endometrial carcinoma 2/4, and stomach carcinoma 1/3. The above indicated usefulness of this agent and further study should be continued, especially a controlled study with adriamycin.

Adult↗
PubMed1982

Compensation techniques in NIRS proton beam radiotherapy.

Proton beam has the dose distribution advantage in radiation therapy, although it has little advantage in biological effects. One of the best advantages is its sharp fall off of dose after the peak. With proton beam, therefore, the dose can be given just to cover a target volume and potentially no dose is delivered thereafter in the beam direction. To utilize this advantage, bolus techniques in conjunction with CT scanning are employed in NIRS proton beam radiation therapy planning. A patient receives CT scanning first so that the target volume can be clearly marked and the radiation direction and fixation method can be determined. At the same time bolus dimensions are calculated. The bolus frames are made with dental paraffin sheets according to the dimensions. The paraffin frame is replaced with dental resin. Alginate (a dental impression material with favorable physical density and skin surface contact) is now employed for the bolus material. With fixation device and bolus on, which are constructed individually, the patient receives CT scanning again prior to a proton beam treatment in order to prove the devices are suitable. Alginate has to be poured into the frame right before each treatments. Further investigations are required to find better bolus materials and easier construction methods.

Aged↗
PubMed1982

[Exploratory study of macromomycin].

Macromomycin, a new antitumor antibiotic (NSC-170105) with significant antitumor activity in animal tumor systems, was administered to 18 patients in an exploratory study. The dose ranged from 1mg to 30 mg per body with a single dose was given. The toxic effects included delayed type leukopenia and thrombocytopenia with nadir of 4 weeks. Except mild upper GI disturbance, no pulmonary, cardiac, hepatic, renal or CNS toxicity was observed. No anaphylaxis was observed in this study. MTD of macromomycin considered to be 26 mg/m2 and optimal administration schedule will be 20 mg/m2 every 6 weeks. Antitumor activity was detected in one patient with ovarian carcinoma with MR in short period.

Adult↗
PubMed1982

[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↗
PubMed1982

[Toxic effects of prolonged oral administration of tegafur (FT-207)].

FT-207 capsules and enteric coated capsules were administered for the chemotherapy of various cancer patients. Twenty-three cases of cancer patients were treated with FT-207 alone orally more than 52 weeks up to 199 weeks continuously with daily dose of 600-800mg with capsules, and 600-1200mg with enteric coated capsules, except one case with markedly light body weight (28kg). There were 3 breast, 1 colon, 1 duodenal, 1 ovary, 11 stomach, 4 hepatic duct, 1 pancreas and 1 double cancer with colon and uterus. Special attention was given to the bone marrow, hepatic, renal, pulmonary and cardiac impairment. There was a mild hepatic enzyme derangement in some cases, but clinically not serious. No meaningful bone marrow, renal, pulmonary or cardiac side reactions were observed. This study confirmed that continuous prolonged oral FT-207 administration was well tolerated and no serious side reactions were observed. However, this was not a controlled study, so that it is still advisable to give oral FT-207 under periodic check up including CBC, SMA-12, chest X-ray and EKG controls.

Administration, Oral↗