Iku Takahashi

Clinical study of the radioprotective effects of amifostine (YM-08310, WR-2721) on chronic radiation injury☆

We have previously reported that Amifostine, a radioprotective agent, was effective in treating acute radiation mucositis in the head and neck region. We found that when a considerable amount of Amifostine accumulates in the salivary glands, it may be useful in preventing chronic disturbances of salivary secretion. We have observed an increase in the uptake of Ga-67-citrate to the salivary glands when they were irradiated. In this paper, the radioprotective effects of Amifostine, in treating chronic radiation injury of the salivary glands, were studied, using the cessation of an increase in uptake of Ga-67-citrate after radiotherapy as the criterion. The subjects were 105 patients, (280 salivary glands in Ga-scintigrams) with malignancy of the head and neck region treated by irradiation from 1978 to 1984. Ga-negative glands were recognized in 97%, that is, 36 out of 37 glands, before irradiation, and the figure decreased to 19%, seven out of 37, within 1 to 2 weeks (10Gy less than or equal to) after the start of radiotherapy. In patients who were irradiated with more than 30 Gy and in whom scintigraphy was performed at 6 months or more after radiotherapy, Ga-negative glands were recognized in 18 out of 41 glands, 44%, with Amifostine, compared with 13%, four out of 32 glands, without Amifostine. A difference was recognized between these two groups in the negative change in Ga-67 uptake after radiotherapy (p less than 0.05). These facts suggest that Amifostine may have a radioprotective effect on chronic radiation injury.

Brachytherapy for penile cancer using silicon mold

We analyzed the treatment results of 15 patients with penile cancer treated by afterloading brachytherapy with a silicon-made mold we devised. The group included 8 patients with T1, 5 with T2 and 2 with T3 tumors, and inguinal lymph node metastases were noted in 4 patients. The total dose of brachytherapy ranged from 32 to 74 Gy with or without an electron beam boost. The median dose rate was 200 cGy/h ranging from 100 to 350 cGy/h. Local control was achieved in 12 of the 15 patients (80%), and was related to the T category, with 100% of T1 and 80% of T2, in contrast to 0% of T3 tumor. Three patients with partial response or residual tumor underwent amputation. Local recurrence was recognized in 1 patient with a T2 tumor, but salvaged by surgery. Penis conservation was achieved in 11 of 15 patients (73%). Of the 4 patients with inguinal lymph node metastases, 3 were controlled by surgery and radiation therapy. The other with a T3 tumor died from the disease. Brachytherapy with a mold for penile cancer was considered to be the first choice for penis-conserving therapy, and the patients with T1 and T2 tumors have good indications for this method of treatment.

Clinical study of radioprotective effects of amifostine (YM-08310, WR-2721) on long-term outcome for patients with cervical cancer

PURPOSE A retrospective analysis was performed to investigate the radioprotective effects of amifostine on the long-term outcome of radiation therapy for the patients with carcinoma of the uterine cervix. METHODS AND MATERIALS Eighty-three patients with histologically proven epidermoid carcinoma (Stage II-IVA disease) of the uterine cervix were treated with definitive radiation therapy between January 1978 and December 1984. Forty-six patients treated with radiation alone, whereas 37 patients treated with radiation plus amifostine. Amifostine was given intravenously 30 min prior to every radiation. Most patients received 75 mg/m2 of amifostine daily from the initiation of the course of radiation therapy. The median total dose of amifostine given was 1300 mg/m2, with a range of 280 mg/m2 to 3700 mg/m2. RESULTS The 5-year overall actuarial survival for the patients treated with radiation alone and with radiation plus amifostine were: 72% and 88% in Stage II disease (p = 0.45); 52% and 50% in Stage III disease (p = 0.68); and 40% and 43% in Stage IVA disease (p = 0.51), respectively. The 5-year intra-pelvic recurrence rates in the patients treated with amifostine were almost the same as those observed in the patients treated without amifostine (0% vs. 6% in Stage II disease; 15% vs. 10% in Stage III disease; 25% vs. 40% in Stage IVA disease). There was also no statistically significant difference of the chronic rectal or bladder complication rate between the groups treated by each regimen. CONCLUSION We concluded that any radioprotective effects of amifostine on tumor tissue and any beneficial effects of amifostine against chronic radiation injury were not observed in the patients with cervical cancer followed up for more than 5 years after radiation therapy.

Palliative Radiotherapy of Bone Metastasis

We analyzed the effects of radiotherapy on 226 sites of metastatic bone tumors from 1981 to 1984, and on 157 sites of bone metastases of prostate cancer from 1970 to 1988. The radiation effect on pain relief was recognized in about 90% of cases within the dose of 20Gy to 30Gy, and there were not many differences in these effects according to the original tumors or histological types. In prostate cancer, the sites which needed re-irradiation were not recognized within 6 months after irradiation, and only 12 out of 80 sites (15%) that could be observed after more than 6 months needed re-irradiation due to recurring pain. As more than 60% of the patients with prostate cancer who needed irradiation to control bone metastases died within a year, to get pain relief by irradiation immediately and safely was thought to be very useful from the viewpoint of useful life. One patient was irradiated on 16 sites and 2 of these 16 sites received 4 treatments of irradiation and the shortest interval was 10 months and the longest one was 18 months.

Hormonal Control of the Lower Esophageal Sphincter in Man and Dog: Reevaluation of the Present Manometric Method for Diagnosis of GE Reflux

Previously, we reported that the contractile activity of the lower esophageal sphincter (LES) and stomach were coordinated during the interdigestive state1,2. Both the LES and stomach cycled between periods of strong contractions and longer periods of quiescence; these data were gathered by long-term measurements made by chronically implanted force transducers in conscious dogs. In the present study, we will report on the effect of gut hormones on LES interdigestive contractile activity in the dog and human.

Clinical usefulness of amifostine (YM-08310, WR-2721) as a radioprotective agent

Radioprotective effects of amifostine were established for acute radiation injury using mucositis in the oral cavity and diarrhea as an index. For chronic radiation injury, radioprotective effects were suggested by the changes in the uptake of Ga-67 citrate in the irradiated salivary glands. Slight adverse reactions appeared, and radioprotective effects on the tumor tissue were not apparent. These results suggested that amifostine can be used as a radioprotective agent in clinical use.<<ETX>>

Clinical Study Of Radioprotective Effects On The Tumor Tissue Of Amifostine(YM-08310, WR-2721). - 5 Years Follow Up Of The Patients

Two hundred and ninety two patients were followed up for 5 years after radiotherapy with administering radioprotective agent ”Amifostine”, and studied about its radioprotective effects on the tumor tissue from the aspect of local recurrence. Local recurrence were observed in only 6 out of overall 292 patients (2%) that might be due to the radioprotective effects of Amifostine. Other local recurrence were observed in 112 patients, but they had been expected their recurrence for their condition as advanced stage and