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R T Mitsuyasu

Publications and source records attributed to R T Mitsuyasu.

77 records · Page 5Linked to original sources

The enhanced potential use of recombinant alpha interferon in the treatment of AIDS-related Kaposi's sarcoma.

Alpha interferon has been extensively studied in the treatment of the epidemic form of Kaposi's sarcoma (KS) common in the acquired immunodeficiency syndrome (AIDS). Its safety and efficacy against KS have been well documented, with objective tumor responses seen in 25%-50% of cases. In a number of large uncontrolled studies, patients had a low incidence of opportunistic infections (OIs) during recombinant alpha interferon therapy. Although several factors may be involved, individuals responding to interferon have a distinct survival advantage over those not responding. Patients with better prognostic features, such as CD4 (T-4/T-helper cell)* counts greater than 200/mm3, no history of OIs, and no lymphoma-like "B" symptoms, are most likely to respond to interferon. Recent studies have identified a soluble growth factor produced by human immunodeficiency virus (HIV)-infected T-lymphocytes, which may be important in the propagation of KS cells in vitro. Studies demonstrating in vivo and in vitro HIV inhibitory effects of alpha interferon and the correlation of antiviral and antitumor responses now suggest that the antiretroviral action of this agent may be critical in the control of KS. Phase I trials of interferon alpha plus the antiretroviral drug zidovudine (azidothymidine, AZT) have shown the combination to be well-tolerated and to produce anti-KS responses at lower doses of each agent than is generally administered. Synergistic antiretroviral activity has been demonstrated with zidovudine and interferon alpha in vitro. Phase II trials of this combination currently are in progress.

Acquired Immunodeficiency Syndrome↗

AIDS Clinical Trials Group Study 094: a phase I/II trial of ABV chemotherapy with zidovudine and recombinant human GM-CSF in AIDS-related Kaposi's sarcoma.

PURPOSE: To define the maximum tolerated dose of doxorubicin when combined with fixed doses of bleomycin, vincristine, zidovudine, and recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) in patients with advanced AIDS-related Kaposi's sarcoma. PATIENTS AND METHODS: Twenty male patients were treated with zidovudine at doses of either 100 or 200 mg by mouth every 4 hours, and cytotoxic chemotherapy with bleomycin 10 U/m2 and vincristine 1.4 mg/m2 by vein every 2 weeks. Four successive cohorts received fixed doses of doxorubicin given intravenously every 2 weeks: two cohorts each received 10 mg/m2 (levels 1, 2) or 20 mg/m2 (levels 3, 4). The first cohort received rhGM-CSF at a dose of 10 micrograms/ kg, given subcutaneously on days 2 through 11 (level 1). Due to toxicity, the dose of rhGM-CSF was reduced to 5 micrograms/kg (levels 2, 3) and then to 2.5 micrograms/kg (level 4). RESULTS: The dose-limiting toxicity was severe neutropenia, occurring in 10 patients. Severe neutropenic episodes occurred after a median of three cycles of chemotherapy, with the nadir occurring after 14 days (median). Moderate neutropenia occurred in 14% of all cycles administered. Constitutional toxicities of moderate or greater severity occurred in four patients. Five of 10 patients at a doxorubicin dose of 20 mg/m2 (levels 3 and 4) experienced severe neutropenia. Thus, doxorubicin at 10 mg/m2, with BV (bleomycin, vincristine chemotherapy), zidovudine (100 mg five times daily), and rhGM-CSF (5 micrograms/kg/day), was defined as the maximum tolerated dose. CONCLUSIONS: The maximum tolerated dose of doxorubicin is 10 mg/ m2 every 2 weeks when given in combination with BV chemotherapy, zidovudine, and rhGM-CSF. While the addition of rhGM-CSF at doses of 2.5 to 5 micrograms/kg decreased the duration of neutropenia, it did not prevent the occurrence of severe neutropenia from combined myelotoxic therapy.

Acquired Immunodeficiency Syndrome↗