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Biomedical subjects

Andrew J Armstrong

Publications and source records attributed to Andrew J Armstrong.

6 recordsLinked to original sources
PubMed2026

Association between smoking, tumor genetics, and outcomes in men with metastatic prostate cancer.

PURPOSE: Smoking has been associated with increased metastatic prostate cancer mortality, but the mechanisms behind this are largely unknown. We hypothesized that smoking increases the risk of genetic alterations associated with aggressive disease and/or the transformation to neuroendocrine prostate cancer (NEPC). PATIENTS AND METHODS: We utilized the Prostate Cancer Precision Medicine Multi-institutional Collaborative Effort (PROMISE) clinical genomic database for this retrospective analysis. We associated patient characteristics and tumor genetic data with smoking exposure at diagnosis (current, former, never and pack years) and with clinical outcomes, including overall survival (OS) from diagnosis or time to developing metastatic disease and NEPC status. RESULTS: We identified 2353 men with prostate cancer and next generation somatic tumor sequencing evaluable for analysis in PROMISE, including 8% current, 39% former, and 52% never smokers. Current smokers were more likely to be younger and to have metastatic (M1 or N1) disease at diagnosis, and less likely to have prior local therapy (all p&#x2009;<&#x2009;0.001). Current smoking was associated with worse OS from diagnosis (99.9 mo vs 137.6 mo, HR 1.42, 95% CI 1.14-1.77), which remained significant after adjusting for disease characteristics. We found no difference in the percentage of NEPC at initial diagnosis or at any time between current, former, and never smokers (p&#x2009;=&#x2009;0.8). We found positive associations between smoking status and genetic alterations in SPOP (current: 15%, former 6.7%, never 3.8%; p&#x2009;=&#x2009;0.018), FGFR1 (current 10%, former 0.4%, never 1.1% p&#x2009;=&#x2009;0.001), and ARID1A (current 5.1%, former 2.2%, never 0.4%; p&#x2009;=&#x2009;0.035) in patients with&#xa0;metastatic androgen pathway modulator sensitive prostate cancer (APMS). CONCLUSION: Active smoking is associated with worse overall and prostate cancer specific survival as compared to never/former smoking and was associated with specific tumor genetic alterations but not small cell/NEPC transformation.

Journal Article↗
PubMed2006

New drugs in prostate cancer.

PURPOSE OF REVIEW: The survival of hormone-refractory metastatic prostate cancer patients has improved with the use of docetaxel-based chemotherapy. The survival benefits, however, are modest suggesting that rationally designed therapeutic approaches are needed. We discuss recent developments in the therapeutic approach to advanced metastatic hormone-refractory prostate cancer, including molecularly targeted therapy, signal transduction inhibitors, stem-cell targeted therapy, anti-angiogenic compounds, vaccines and immunomodulating agents, differentiation agents, cytotoxics, and pro-apoptotic agents. RECENT FINDINGS: Over 200 compounds have entered clinical development for use in advanced prostate cancer, alone or in combination with cytotoxic agents such as docetaxel, or in other combinations. This article will review the results of emerging targets since the approval of docetaxel in 2004, concentrating on some of those compounds that, in our opinion, have the greatest potential and rationale for use. SUMMARY: The growing field of targeted molecular therapy of prostate cancer has opened up numerous opportunities for therapeutic impact. Knowledge of the molecular determinants of progression, relapse after local therapy, chemotherapeutic resistance, and hormone refractoriness remains essential in the rational design of clinical trials of these agents. Given the complexity, heterogeneity, and crosstalk of molecular pathways and the molecular lesions in prostate cancer, combination or sequential therapy may be a necessary step towards significant therapeutic progress. Novel translational clinical trial methodologies may assist in a more rapid identification of active compounds at biologically active doses for phase-III testing.

Androgen Antagonists↗
PubMed2005

Chemotherapy for advanced prostate cancer: results of new clinical trials and future studies.

Our understanding of the role of chemotherapy for advanced prostate cancer has improved considerably in 2004 with the publication of two large randomized phase III trials and the approval by the US Food and Drug Administration of docetaxel and prednisone for metastatic hormone-refractory disease. Although treatment is still considered palliative in nature, studies of chemotherapy for metastatic hormone-refractory prostate cancer (HRPC) have demonstrated improved overall survival compared with older regimens as well as clinically significant improvements in important endpoints, such as quality of life and time to progression. In particular, docetaxel has emerged as first-line therapy on an every-3-week schedule for metastatic HRPC, replacing mitoxantrone, as recently reported in the TAX327 trial. Docetaxel and estramustine combinations have the disadvantage of significant cardiovascular and gastrointestinal toxicity, and further use of estramustine is likely unwarranted as first-line therapy. Future trials examining novel biologic agents and combination therapies should use single-agent docetaxel as the reference standard. The role of chemotherapy for advanced disease in the neoadjuvant or adjuvant setting, in biochemically (PSA) relapsed patients, and as second-line therapy for relapsed disease, remains a subject of active clinical investigation.

Antineoplastic Agents↗
PubMed2005

Advanced prostate cancer: the future.

The demonstration of a survival benefit with docetaxel for the treatment of metastatic hormone refractory prostate cancer (HRPC) is an important step forward in advancing treatment options for advanced prostate cancer. While docetaxel-based therapy has demonstrated improvement in symptomatic and quality-of-life endpoints, certainly there is a pressing need for improvement in outcomes. A number of novel agents are in basic and clinical development for advanced prostate cancer, some of which are specific to mechanisms that may be important in the development and spread of prostate cancer. Novel approaches including novel cytotoxics, immunotherapy, PSMA targeted monoclonal antibodies are among the broad categories that will be discussed in this brief review.

Antibodies, Monoclonal↗
PubMed2005

Novel therapeutic approaches to advanced prostate cancer.

Considerable progress in the treatment of advanced prostate cancer was made in 2004 with the approval by the US Food and Drug Administration of docetaxel for the treatment of metastatic hormone-refractory prostate cancer. The survival benefit with docetaxel and prednisone, however, has been modest, on the order of 2-3 months compared with mitoxantrone and prednisone. While docetaxel-based therapy has demonstrated improvement in symptomatic and quality-of-life endpoints, certainly there is a pressing need for improvement in outcomes. A number of novel agents are in basic and clinical development for advanced prostate cancer, some of which are specific to mechanisms that may be important in the development and spread of prostate cancer. Novel approaches including immunotherapy, antiangiogenic compounds, and cell growth and survival pathway inhibitors, as well as targeted cytotoxic compounds, are among the broad categories that will be discussed in this review. Clinical advances in meaningful endpoints such as survival and quality of life are eagerly awaited in large-scale trials of active and rationally designed agents.

Adenocarcinoma↗