Clin Cancer Res
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Clinical Trial
Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver.
Liver metastases are the sole or life-limiting component of disease in the majority of patients with ocular melanoma who recur. Because median survival after diagnosis of liver metastases is short and no satisfactory treatment options exist, we have conducted clinical trials evaluating isolated hepatic perfusion (IHP) for patients afflicted with this condition. ⋯ IHP with melphalan alone results in significant regression of established liver metastases for patients with ocular melanoma. However, after IHP, disease progression is most commonly observed in the liver, and survival after disease progression is short. On the basis of a pattern of tumor progression predominantly in liver, continued clinical evaluation of hepatic directed therapy in this patient population is justified.
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Clinical Trial
Phase I and correlative study of combination bryostatin 1 and vincristine in relapsed B-cell malignancies.
Bryostatin 1 activates protein kinase C (PKC) with short-term exposure and results in depletion of PKC with prolonged exposure. Preclinical in vitro and in vivo studies demonstrate synergistic activity and increased tumor apoptosis in B-cell malignancies when a prolonged infusion of bryostatin 1 is followed by vincristine. ⋯ Given the lack of myelosuppression and early evidence of clinical efficacy, additional exploration of this regimen in non-Hodgkin's lymphoma and multiple myeloma is warranted.
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Induction chemotherapy with carboplatin and paclitaxel followed by concomitant TFHX (paclitaxel, infusional 5-fluorouracil, hydroxyurea, and twice-daily radiation therapy administered every other week) has resulted in 70% 3-year survival in stage IV patients. Locoregional and distant control rates were 94 and 93%, respectively. In an attempt to decrease toxicity without compromising local control, a second cohort of patients was treated with a lower dose of radiation to sites of potential microscopic disease. ⋯ In this second trial, induction chemotherapy with carboplatin and paclitaxel followed by TFHX chemoradiotherapy results in high survival and progression-free survival. The reduction in radiation dose did not compromise survival or disease control compared with our prior study using higher radiation doses. Data continues to support definitive evaluation of this approach.
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This study was conducted to assess the feasibility of administering the oral diarylsulfonylurea (DSU) ILX-295501 on a weekly for 3 weeks every 4-week schedule. The study also sought to determine the maximum tolerated dose (MTD) of ILX-295501 on this schedule, characterize its pharmacokinetic behavior, and seek preliminary evidence of anticancer activity. ⋯ The recommended dose for Phase II studies of the oral DSU ILX-295501 administered weekly for 3 weeks every 4 weeks is 1000 mg/m(2)/day for both minimally pretreated and HP patients. The characteristics of the myelosuppressive effects of ILX-295501, the paucity of severe nonhematological toxicities, and preliminary antitumor activity warrant disease-directed evaluations of ILX-295501.
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Comparative Study
Endometriosis and its treatment with danazol or lupron in relation to ovarian cancer.
It has been hypothesized that circulating androgens may be involved in the development of ovarian cancer. The androgenic medication, danazol, and the antiandrogenic medications, leuprolide and nafarelin, are commonly used in the treatment of endometriosis. We assessed the associations between the use of these medications and ovarian cancer. ⋯ Danazol, but not leuprolide/nafarelin, increased the risk of ovarian cancer. This supports the hypothesis that androgen excess may be associated with the development of ovarian cancer.