[High dose methotrexate with CF rescue therapy in patients with head and neck cancer].

A clinical trial of high dose methotrexate (MTX)-CF rescue was conducted in 17 institutions. Forty-seven patients with head and neck cancer entered this trial, of which 29 were evaluable. In this series, the patients were divided into 2 groups (Arm I, Arm II), according to physician's selection. MTX was administered 700 mg/m2 (1000 mg/body) in Arm I and 1750 mg/m2 (2500 mg/body) in Arm II by i.v. drip over 6 hours. Twenty-four hours after initiation of MTX infusion, CF rescue was started. There was no complete response in 29 patients. Four patients showed partial response with an overall response rate of 13.8%. There were 4 partial responders out of 21 patients in Arm I, with a response rate of 19%, whereas there was no partial responders out of 8 patients in Arm II. These results showed no apparent dose response. MTX concentrations in plasma were determined at 6, 24, 48 and 72 hours after initiation of MTX infusion. The assay results revealed a safe range in Arm I, but exceeded in 3 cases of Arm II. GI disturbances were seen at the rate of 78%. Bone marrow suppression was remarkable and hepatic toxicity was observed as the rate of 41%. No renal toxicity was observed. The results of high dose MTX-CF rescue therapy were not better than those of moderate dose therapy, so that we concluded that MTX should be used as one agent at low or moderate dose in combination chemotherapy as far as Japanese patients with head and neck cancer are concerned.

Inhibition of stomal recurrence in laryngectomy with preoperative far therapy. A statistical evaluation.

FAR therapy is effective for cancers of the head and neck, in particular laryngeal cancer. This combined chemoradiotherapy consists of 5-FU, vitamin A and radiation. We found 10% stomal recurrences in reviewing 112 patients who had been treated with total laryngectomy. Stomal recurrences after total laryngectomy occur frequently in patients undergoing an emergency tracheotomy. We studied 33 such patients divided into 2 groups, on the basis of whether laryngectomy had been carried out after the emergency tracheotomy plus preoperative FAR therapy, or whether laryngectomy had been carried out without preoperative FAR therapy. The incidence of stomal recurrence was less among those given preoperative FAR therapy and was statistically significant. Such being the case, preoperative FAR therapy seems to e prophylactically effective against stomal recurrence after emergency tracheotomy.

Surgical treatment of the laryngotracheal amyloidosis.

Two cases of primary localized amyloid tumor in the larynx and trachea surgically treated were herein reported. As recurrence of the amyloid tumor might lead to repeated resection in the same region, first trial of eradicative laryngofissure or laryngotracheofissure proved to be the effective approaches. The denuded area of the respiratory tract after removing amyloid tumor was covered with a split thickness skin graft and/or neighbouring mucosa applying soft rubber stent, then extensive scarring and schrinkage of the airways after surgery could thus be eliminated.

[Moderate dose methotrexate with citrovorum factor rescue therapy in the treatment of head and neck cancer].

A clinical trial of moderate dose methotrexate (MTX)-CF rescue was conducted in 12 institutions. Thirty-seven patients with head and neck carcinoma entered this trial, of which 32 were evaluable. MTX was administered 350 mg/m2 (500 mg/body) by i.v. drip over 6 hours. Three hours after completion of MTX infusion, CF rescue was started. There was no complete response in 32 patients. Nine patients showed partial response with the response rate of 28%. The response rates were 21% for the group of patients treated previously, and 75% for the group untreated previously. MTX concentration in plasma was determined at 6, 24, 48 and 72 hours after the initiation of MTX infusion, and the assay results revealed a safe range. GI disturbances were seen at the rates of 11 to 38%. Bone marrow suppression was mild and no renal toxicity was observed. We concluded that the moderate dose MTX-CF rescue therapy was useful for head and neck carcinoma. As a next step, we are planning to conduct a clinical trial of high-dose MTX.

[Antitumor effect of UFT against malignant tumors of maxillary sinus--clinical and biochemical study].

Antitumor effect of UFT against malignant tumors of the maxillary sinus (male 8, female 5) was examined clinically and biochemically. According to the Karnofsky's criteria, the clinical effectiveness was demonstrated as follows; I-B: 1, I-A: 2, 0-C: 1, 0-B: 2, 0-A: 2, 0-0: 4, unknown: 1. While according to a Japanese Criteria for Evaluation of Clinical Effects of Cancer Chemotherapy on Solid Tumors the results were assessed as follows: CR: 1, PR: 3, NC: 3, PD: 5, unknown: 1. Generally side effect was mild and found in four patients. 5-FU levels in tissue specimens of the two patients were determined. 5-FU levels in the tumor tissues were 1.3 and 2.4 times higher than those of the normal tissues, respectively.

Local immune system in the developing fetal larynx.

Using histopathological and immunofluorescent techniques, we investigated the development of the glandular system of the larynx from 12 human fetuses. Glandular buds were first observed at the fourth month of gestation and glandular distribution became evident from the fifth month in the larynx. Ciliated or nonciliated epithelium covered the cavity of the larynx, with the exception of the true vocal cord. Immunofluorescent examination revealed the presence of IgG in the fetal larynx, but there was little fluorescence for IgA, IgM and IgE. Secretory component (SC) synthesis, on the other hand, was found in each serous-type glandular epithelium or acinus from the fourth month on. Our observations suggest that the local immune system by SC, which binds to IgA as SIgA in human laryngeal mucosa, is inherently acquired in the fetal larynx.

Immunopathological study of the larynx. IgA distribution and secretory activity.

Using immunofluorescent and histopathological techniques, we studied the distribution and secretory activity of the glands of the larynx from 55 humans. The cavity of the larynx was covered with secretory glandular cells with the exception of the true vocal cords, aryepiglottic folds and upper part of the laryngeal surface of the epiglottis. Immunofluorescent study revealed the presence of IgG and other immunoglobulins throughout the connective tissue ground in each laryngeal mucosa. The most striking was seen in the staining pattern of IgA. Diffuse fluorescence for IgA was observed not only in the submucosal or periglandular connective tissue area but also in the intraeptithelial or submucosa glands. Secretory component synthesis was found mainly in each serous-type glandular epithelium or acinus. In the submucosa or periglandular area, IgA producing plasma cells were numerous. Our observations suggest that IgA, produced locally, is secreted via the glandular cells as secretory component--SIgA. Secretory activity of SIgA in these glandular tissues indicates that the larynx is possibly an immunologically active organ in the upper respiratory tract.

Establishment of a new cell line from maxillary sinus carcinoma.

We succeeded in deriving a long-term tissue culture cell line from human maxillary sinus carcinoma. This cell line, designated as MC, was passaged 100 times in vitro over a period of 18 months. The cells are globular in shape, grow as single cells in the culture medium, and the mean population doubling time is about 12 hours. The plating efficiency rate in soft agar is 78% and chromosomal analysis revealed the modal chromosome number to be between 47 and 51. These MC cells were transplanted into five nude mice, all of which developed a tumor after a latency period of 5 to 8 days and died within 39 days. Complete autopsy of all mice revealed no metastasis. Histopathological findings of the original and the transplanted tumor tissues showed a remarkable similarity.

Synergistic combination therapy of 5-fluorouracil, vitamin A and cobalt-60 radiation upon head and neck tumors.

We have applied a triple combination of 5-fluorouracil (5FU), vitamin A and cobalt-60 radiation (FAR therapy) to clinical treatment of head and neck tumors since 1972. The treatment of 33 patients with cancer of larynx and 15 patients with hypopharyngeal or cervical esophageal cancer with FAR therapy during three years from 1972 to 1974 resulted in highly effective synergism in vivo, and the improved points of this therapy were presented.