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The effect of prostaglandin E1 (PGE1) on liver dysfunction due to high-dose methotrexate (HD-MTX) was investigated in children with malignant diseases. Eight children received 45 doses of HD-MTX. Group 1 (33 cases) received no PGE1. Group 2 (4 cases) received PGE1 intravenously 8 times every 12 hours for 3 consecutive days. Group 3 (8 cases) received infusion of PGE1 continuously for 4 days (1 day before and 3 consecutive days after MTX infusion). No significant difference was observed among the serum levels of transaminase in these 3 groups as well as the corresponding levels in the same patients who were treated with or without PGE1. There are reports suggesting that in spite of the lack of any difference in serum transaminase levels in rats with drug-induced hepatic injury given PGE1 infusion, data on DNA synthesis and survival ratio indicate the existence of 'hepatocytoprotection'. Further investigation will be necessary in order to decide whether PGE1 infusion is indeed effective.

Seven children with advanced solid tumors (2 rhabdomyosarcomas, 2 Ewing's sarcomas, 1 astrocytoma, 1 T cell lymphoma and 1 neuroblastoma) received high dose chemotherapy and/or radiotherapy followed by autologous bone marrow transplantation. Four patients achieved complete remissions, two had partial remissions, and one was no response. Side effect of autologous bone marrow transplantation was few compared with that of allogeneic bone marrow transplantation in which graft versus host reaction, profound posttransplantation immunodeficiency and interstitial pneumonitis were unavoidable. In this report methods of bone marrow cryopreservation and elimination of tumor cells from harvested bone marrow were also discussed.

A cooperative multicenter clinical study on cisplatin in children with malignant solid tumors was conducted in seventeen institutions. Of 63 children entered into the study, 18 patients were treated with cisplatin alone, 33 with a VCAP regimen (VCR, CPA, ADM and CDDP) and 12 with other combination regimens. The numbers of evaluable patients were 14, 27 and 7, respectively. Response rates for neuroblastoma were 37.5% (3/8) with cisplatin alone and 79.2% (19/24) for the VCAP regimen. Major adverse effects were gastrointestinal symptoms, bone marrow suppression and renal impairment. Hearing difficulty, electrolyte imbalance and transient elevation of transaminase were also observed. However, these adverse effects were within a tolerable range of severity. The results of this study demonstrate that cisplatin is a useful drug in the treatment of neuroblastoma.

Alpha and beta interferon were tested for antitumor activity and clinical toxicity in 15 children suffering from cancer. The drug was administered IV, IM, IT or intralesionally daily in the majority of cases in total doses of 18 X 10(6) to 9,634 X 10(5) IU. Major toxicities were a flulike syndrome, elevation of transaminase activity and leukopenia. A minor response (less than 50%) was observed in one patient with glioblastoma, treated by intrathecal administration, and an objective local response was noted in one rhabdomyosarcoma patient with multiple subcutaneous metastases, who was treated by intralesional administration. CNS leukemia in two patients improved without hematological response. Further trials are warranted.

Comparative study of antiemetic effect on vomiting due to cancer chemotherapy was performed in 62 children with various malignant diseases. Twenty-one children were treated with metoclopramide, 23 children with domperidone and remaining 18 children received methylprednisolone. Each drug was administered intravenously after administration of anticancer agents, and repeated if necessary. The most effective antiemetics was methyl-prednisolone with effective rate of 89% in comparison with 51% of domperidone and 17% of metoclopromide treated group, respectively. Methyl-prednisolone may be useful for severe vomiting due to anticancer drugs. Safer and significantly better therapeutic efficacy was observed in the group treated with domperidone than that with metoclopromide.

N-myc, which has partial sequence homology to the oncogene c-myc, was isolated from human neuroblastoma cell lines. We have surveyed amplification of N-myc, clone 8 and pG21 in human neuroblastoma cell lines, xenografts and in primary tumors and found that amplification frequently occurred in tumors classified as stage III and IV. In situ hybridization studies demonstrated that in neuroblastomas, chromosome aberrations such as HSR (homogeneously staining region) and DMs (double minutes) are cytological manifestations of the amplification of these clones. The N-myc-related gene seems to contribute to cell growth or differentiation of the nerve cell and its amplification with enhanced expression promotes the progression of the tumor with poor prognosis.

Seventy-nine patients with rhabdomyosarcoma (RMS) received treatment at the National Cancer Center Hospital between 1962 and 1985. The patients ranged in age from 4 months to 74 years with a median age of 6 years. Forty-six patients were male and 33 were female. The primary tumor site of RMS was the same as in the previous report. The head and neck region was the most frequent site (40.5%), followed by the extremities (34.1%), genitourinary region (15.2%), trunk (5.1%) and retroperitoneum (5.1%). Histologic types were embryonal RMS in 45 patients, alveolar RMS in 23 patients, pleomorphic RMS in 8 patients and unclassified RMS in 3 patients. As of October 1985, 14 of the 79 patients were still alive. Between 1962 and 1971, 38 patients were not treated by any protocol. After 1972, 41 patients received treatment using a 3 stage-related, multiple-modality program. In the first protocol, chemotherapy consisted of Vincristine, Cyclophosphamide, and Actinomycin-D, and 1 of 18 patients have survived more than 5 years. The cumulative 5-year survival rate of the first protocol was 11.1%. In the second treatment program, which involved Adriamycin in addition to the 3 drugs cited above, 4 of 23 patients have survived more than 5 years. The cumulative 5-year survival rate, 33.2%, was very improved.

Sixty-six cases of multiple primary neoplasms in children in Japan were collected, including 8 cases of our own. These could be divided into 19 synchronous and 47 metachronous multiple neoplasms. Metachronous or multiple primary neoplasms comprised leukemia, osteosarcoma, mesenchymal sarcoma, epithelial carcinoma and others in contrast to synchronous neoplasms which consisted of many pairs of embryonic tumors. The presumptive factors for multiple primary neoplasms suggested radiotherapy-associated cancers in 30%, radiochemotherapy-associated in 13%, chemotherapy-associated in 34%, and genetic factor-related in 36% of cases. Chromosomal analysis was performed in 12 cases. Three of 4 leukemias revealed major karyotypic abnormalities in the leukemic cells. No 13q14, deletion was detected in 5 cases with multiple primary neoplasms developed with retinoblastoma. Frequent incidence of sister chromatid exchange (SCE) was detected in cultured fibroblasts or lymphocytes from one of 3 cases of second primary neoplasms associated with chemotherapy. The time interval between both neoplasms ranged from 2 to 15 years in the majority of cases. Chemotherapy-associated multiple primary neoplasms seemed to appear more quickly than radiotherapy-associated multiple primary neoplasms. Seven children out of 459 long-term survivors of childhood cancer developed multiple primary neoplasms during the period from 5 to 20 years after diagnosis of the first tumor at the National Cancer Center Hospital, Tokyo. The relative risk was suggested to be 14 times higher than the expected incidence of childhood cancer in Japan. Refinement of treatment, long-term monitoring and protective procedures for high-risk patients against multiple primary neoplasms are therefore warranted.

The clinical effects of a new anti-viral 9-(2-hydroxymethoxymethyl) guanine (Aciclovir) against Herpes virus infections have been investigated. The patients had malignant tumours or auto-immune disease complicated by shingles and chicken pox due to Vaicella zoster virus (VZV) (43 cases), Herpes simplex virus (HSV) (10 cases) and 9 cases which were clinically diagnosed as Herpes, though the virus was not confirmed as the causative agent. As a general principle the dosage of Aciclovir was 5 mg/kg, t. i. d. for 5 days by slow intravenous infusion. The clinically effective rate against VZV was 93%, being excellent in 42% and against HSV it was 80%, being excellent in 40% and when the results of the cases of unknown origin were included it was excellent in 40% and the cumulative effective rate was 88%. Concerning the efficacy in reduction of pain, swelling, disappearance of vesicles and new scab formation, the effect was most noticeable after the third day of treatment. Treatment given early in the disease is likely to provide better results. Concerning side effects, one of 62 patients had proteinuria and the other had a drug rash and an abnormal liver function test. It is likely that the combination of treatment and the primary disease had some influence, but the cause/effect relationship to Aciclovir treatment is not clear.