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Biomedical subjects

C T Tan

Publications and source records attributed to C T Tan.

At least 127 records · Page 7Linked to original sources

Phase I study of aziridinylbenzoquinone (AZQ, NSC 182986) in children with cancer.

Aziridinylbenzoquinone is a quinone compound capable of penetrating the central nervous system. It has demonstrated activity against both intracranial and i.p. murine tumors and human tumor xenographs. We have conducted a Phase I trial of aziridinylbenzoquinone in 60 children with advanced cancer who were refractory to conventional therapy. The drug was given by slow i.v. push on a daily schedule for 5 days every 3 to 4 weeks. The dose range explored included 6 dose levels, ranging from 6 to 12 mg/sq m daily for 5 days in patients with solid tumors and leukemia, and in patients with leukemia, 20, 25, and 30 mg/sq m daily for 5 days. Myelosuppression was the dose-limiting side effect. In patients with solid tumor the highest dose studied was 12 mg/sq m, and the median nadir white blood cell and platelet counts were 0.7 X 10(3) and 6.0 X 10(3)/microliter on Days 17 and 22, respectively. The median recovery day for white blood cells was 39. There may be some evidence of cumulative toxicity with prolonged thrombocytopenia. Other side effects were mild nausea, vomiting, and mucositis. Elevations in liver enzymes and bilirubin were transient and dose dependent, occurring 3 to 4 weeks after drug administration. Of the 34 children with solid tumors, 33 were evaluable for hematopoietic toxicity, 3 were early deaths, and 31 receiving a total of 55 courses were evaluable for therapeutic response. Partial responses lasting 3 weeks to 6 months were seen in the 4 patients with Hodgkin's disease, and in a child with a metastatic spinal cord ependymoma. Fifty-two courses were given to 9 patients with acute lymphocytic leukemia and 17 with acute nonlymphoblastic leukemia. Of the 15 patients with acute nonlymphoblastic leukemia treated at doses greater than or equal to 25 mg/sq m/day for 5 days there was one early death and there were 2 M1 (less than or equal to 5% blasts with normal cellularity), 3 M2A (6 to 15% blasts), and 2 M2B (16 to 39% blasts) bone marrow responses lasting 1 to 3.5 months. Aziridinylbenzoquinone demonstrated activity against acute nonlymphocytic leukemia with maximal tolerated doses of 30 mg/sq m daily for 5 days. Its effect in Hodgkin's disease is encouraging; however, further study will be required to determine its efficacy in central nervous system cancers. Recommended doses for Phase II studies, using daily schedule for 5 days in children with solid tumors, is 9 mg/sq m, and in children with leukemia, it is 25 mg/sq m.

Adolescent↗

Language function and dysfunction among Chinese- and English-speaking polyglots: cortical stimulation, Wada testing, and clinical studies.

Language functions in a group of Chinese- and English-speaking polyglots living in a multiracial society have been investigated by several methods: the effects of cortical stimulation on object-naming and reading tasks in patients who required awake craniotomy, lateralization of cerebral dominance for speech by the Wada Test, and the pattern of language loss and recovery following stroke. The data indicate that these polyglots were all left hemisphere dominant for the languages tested: no consistent evidence for increased participation by the right hemisphere for language functions was found. The cortical stimulation experiments provided data most compatible with the "differential localization" model of cerebral localization in bilingualism. The variable which most influenced performance in all of these investigations was which language was used primarily for speaking as well as reading and writing at the time of the study.

Adult↗

Phase I evaluation of 2'-fluoro-5-iodo-1-beta-D-arabinofuranosylcytosine in immunosuppressed patients with herpesvirus infection.

2'-Fluoro-5-iodo-1-beta-D-arabinofuranosylcytosine (FIAC) is a potent selective inhibitor of the replication of herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella zoster virus, and cytomegalovirus in cell culture systems. FIAC produces an unequivocal therapeutic effect in mice that have been inoculated with a lethal burden of HSV-1. We have administered FIAC to 32 host compromised patients, 30 with advanced cancer, who were experiencing acute herpesvirus infections (varicella zoster, 29; HSV-1, 2; HSV-2, 1); the drug was given by 20 min i.v. infusion twice a day for 7 days. The dosage levels explored were 60, 120, 240, 400, and 600 mg/sq m/day. Drug-induced myelosuppression became evident at 600 mg/sq m/day; thrombocytopenia exceeded leukopenia. The toxic low dose was 400 mg/sq m/day with mild nausea and rare myelosuppression. All 24 varicella zoster patients with cutaneous disease receiving FIAC, greater than or equal to 120 mg/sq m/day, experienced stabilization of cutaneous lesions within 48 to 72 hr; healing began promptly thereafter.

Antiviral Agents↗

Phase II study of 4'-(9-acridinylamino)methanesulfon-m-anisidide (NSC 249992) in children with acute leukemia and lymphoma.

Phase I clinical studies of 4'-(9-acridinylamino)methanesulfon-m-anisidide (AMSA) using several dose schedules have shown acceptable toxicity and antitumor responses in acute leukemia and several carcinomas. Thirty-eight children with acute leukemia and non-Hodgkin's lymphoma were treated with AMSA in a total dose of 140 to 600 mg/sq m given as a daily i.v. infusion in 2 to 5 days. Maximal tolerated dose was 600 mg/sq m given in 5 days. Complete and partial remissions were seen in four of 18 patients with acute lymphocytic leukemia, zero of eight patients with acute nonlymphocytic leukemia, and one of five patients with non-Hodgkin's lymphoma. Marrow aplasia and remissions were also seen with lower doses. The major toxic effects were mucositis, fever, and sepsis which were dose related. Mild nausea and vomiting, transient elevation of serum glutamic oxaloacetic-acid-transaminase, and bilirubin were noted. All of these patients had had prior anthracycline therapy. Abnormal echocardiograms were seen in 14 of 23 patients who had echocardiograms done before and after AMSA. Seven developed congestive heart failure in association with sepsis in five and with epicardial disease in one. We conclude that AMSA possesses significant activity in childhood leukemia and lymphoma and that studies of AMSA in combination with other effective agents should be done.

Acute Disease↗

Distinguishing features of the immunology of Hodgkin's disease in children.

Laboratory tests of immunologic function were done in 96 children with Hodgkin's disease, at diagnosis and during and after treatment. Over the same period of time, 29 aged-matched control children were tested. The results presented in this report indicate that the immunology of childhood Hodgkin's disease has some features that distinguish it from the immunologic features of the disease in adults: (a) no progressive lymphopenia was found with advanced clinical stages; (b) peripheral blood T-lymphocyte counts were normal or high, and slight B lymphocytopenias were observed in children at all stages of the disease; (c) in spite of normal T-lymphocyte counts, a defective response to phytohemagglutinin stimulation was seen at diagnosis; and (d) recovery of the phytohemagglutinin response occurred with treatment and was related to modality of therapy and prognosis.

Adolescent↗

Hodgkin's diseases in adolescents presenting as a primary bone lesion. A report of four cases and review of literature.

Bone involvement of Hodgkin's disease usually occurs late in the course of the illness, together with extensive nodal involvement. In the past 5 years, we have seen four adolescents with Hodgkin's disease who presented with primary bone lesions. All had disseminated lymphoid involvement when the final diagnosis was made 3-11 months later. A review of the literature showed 13 more cases of similar presentation. The patient characteristics are discussed and the diagnostic difficulties are emphasized. Hodgkin's disease should be considered in the differential diagnosis of primary osseous malignancies.

Adolescent↗

Phase I trial of rubidazone (NSC 164011) in children with cancer.

Rubidazone was administered to 24 children with advanced solid tumors or leukemia. The dose ranged from 80 to 150 mg/m2/IV daily to a total dose of 160 to 450 mg/m2/course. This course was repeated at intervals of approximately three weeks. Eighteen of 24 patients (75%) had received adriamycin and daunomycin as part of prior chemotherapy. The major toxic effects observed were myelosuppression, nausea, vomiting, mucositis, and skin rash. Four patients developed abnormal echocardiograms following the rubidazone therapy, 2 manifested clinical cardiac failure, of which one had anthracycline cardiomyopathic changes on autopsy. One of 7 adequately treated ALL patients achieved M2 marrow and improved peripheral counts for 3 weeks. One of the 2 neuroblastoma patients had subjective improvement of bone pain for 2 months. Rubidazone, in a previous heavily treated group of patients used in this study, had dosages of 360 and 450 mg/m2 which produced marrow hyperplasia to aplasia, with only minimal responses.

Adolescent↗

Specific anti-thyroxine antisera induced by thyroxine sensitized liposomes.

Specific anti-thyroxine rabbit antisera were generated from complete Freund's adjuvant with liposomes consisting of sphingomyelin, cholesterol, dicetylphosphate and 5-N-thyroxine-2,4-dinitrophenyl-phosphatidylethanolamine (T4-Dnp-PE). Spin membrane immunoassay technique was used to measure the sensitivity and specificity of these antisera. Addition of 10 to 70 ng of L-thyroxine produced significant inhibition of immune lysis. Addition of L-3,3',5-triiodothyronine (T3) up to 800 ng showed no cross reaction.

Amines↗