American journal of clinical oncology
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Am. J. Clin. Oncol. · Oct 2003
Intermittent androgen deprivation for patients with recurrent/metastatic prostate cancer.
This study was designed to assess the duration of response to intermittent androgen deprivation therapy (IAD) in patients with recurrent and/or metastatic prostate cancer. Between January 1993 and March 2000, 74 patients with recurrent and/or metastatic prostate cancer had IAD with either luteinizing hormone-releasing hormone agonist (LHRH) or an LHRH with an oral antiandrogen. Forty-one patients were treated for an increasing prostate-specific antigen (PSA) level after primary local treatment. ⋯ For the subgroups of patients treated for biochemical failure, locoregional recurrence, and bone metastases, the 4-year actuarial progression-free survival rates were 80%, 67%, and 45% respectively (P = 0.018). The median time of 18 months to progression in patients with bone metastases is similar to that reported with continuous hormonal therapy. In patients with biochemical failure, the median time to progression (more than 5 years) suggests that the IAD approach may be a viable option for this group of patients.
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Am. J. Clin. Oncol. · Aug 2003
Impact of hormone therapy when combined with external beam radiotherapy for early-stage, intermediate-, or high-risk prostate cancer.
The purpose of this investigation was to explore the potential benefit of hormone therapy in addition to external beam radiotherapy for patients with early-stage (T1-2), intermediate-(prostate-specific antigen [PSA] > 10 or Gleason score >or= 7) or high-risk (PSA > 10 and Gleason score >or= 7) prostate cancer. The charts of 412 patients with early-stage intermediate- and high-risk prostate cancer treated with external beam radiotherapy with or without a 4-month total androgen blockade were reviewed. The groups were balanced with respect to age, pretreatment PSA, and stage, but differed with respect to Gleason score and radiation dose. ⋯ This difference was seen for the subgroups followed for more than 6 months (12.5 vs. 25.0%), more than 9 months (14.5 vs. 26.3%), and more than 12 months (17.3 vs. 27.0%). Thus, biochemical failure decreased with the administration of hormone therapy in this group of patients with early stage, intermediate- or high-risk prostate cancer. This finding requires validation by ongoing randomized trials.
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Am. J. Clin. Oncol. · Aug 2003
Celecoxib reduces skin damage after radiation: selective reduction of chemokine and receptor mRNA expression in irradiated skin but not in irradiated mammary tumor.
Inflammatory cytokine and chemokine production is mediated, at least in part, by prostaglandin E (PGE2). Cyclooxygenases, COX-1 and COX-2, are two key enzymes in the conversion of arachidonic acid to PGE2. Radiation induces the overproduction of cytokines and chemokines, and it also increases PGE2 production, both locally and systemically. ⋯ A significant positive correlation was also found between skin damage (skin scores) and chemokine and its receptor mRNA expression in radiation-treated mice. Finally, celecoxib also decreased the infiltration of monocytes and neutrophils in locally irradiated tumor and surrounding normal tissue. The differential effects of celecoxib on inflammation help to explain the selective protection by celecoxib of irradiated cutaneous tissues without a concurrent protection of MCa-35 tumors.
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Am. J. Clin. Oncol. · Aug 2003
Combination of radiation and celebrex (celecoxib) reduce mammary and lung tumor growth.
The selective cyclooxygenase (COX)-2 inhibitor, celecoxib, alone and in combination with radiation was investigated in vitro and in vivo. Murine mammary tumor line (MCa-35) and human lung carcinoma line (A549) have high and low basal levels of COX-2 protein, respectively. Treatment of both tumor cells with celecoxib alone resulted in a dose- and time-dependent reduction of cell number (clonogenic cell death) and tumor cell growth rate in vitro; however, inhibition of tumor cell growth by celecoxib was not correlated with the reduction of COX-2 protein in tumor cells. ⋯ Reduction of tumor angiogenic cytokine and growth factor mRNA was associated with decreased perfused vessels. Finally, reduction of vascular endothelial growth factor protein after celecoxib was also observed in both tumor lines by Western blot. Our results indicate that the selective inhibition of COX-2 combined with radiation has potential application in radiotherapy, and celecoxib-mediated antitumor effects may act through different mechanisms including direct inhibition of tumor cell proliferation, alteration of tumor cell cycle, and antiangiogenesis.
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Am. J. Clin. Oncol. · Aug 2003
Selection of patients with melanoma brain metastases for aggressive treatment.
The purpose of this study was to determine prognostic factors for patients with melanoma brain metastases that can be recommended for patient selection for clinical trials. A retrospective review was conducted of 65 patients irradiated for brain metastases from 1990 to 1997. Pretreatment factors analyzed for influence on survival included age, stage, Karnofsky Performance Status (KPS), extracranial metastases, the number and location of brain lesions, disease-free interval from initial diagnosis, total dose of radiation, and number of fractions administered. ⋯ Both factors remained significant on multivariate analysis. The prognosis of patients receiving radiotherapy for brain metastases is related to RPA class, the presence of extracranial metastases, and KPS. These criteria should be employed in selecting patients for aggressive protocol treatment, or for more protracted brain irradiation off protocol.