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Biomedical subjects

Cora N Sternberg

Publications and source records attributed to Cora N Sternberg.

At least 19 recordsLinked to original sources
PubMed2006

Effective chemotherapy for hormone-refractory prostate cancer (HRPC): present status and perspectives with taxane-based treatments.

Prostate cancer is a significant health concern for men worldwide. It continues to be the most common lethal malignancy diagnosed in American men and the second leading cause of male cancer mortality. Hormone-refractory prostate cancer (HRPC) remains clinically challenging. Two large phase III studies have demonstrated a survival advantage in HRPC patients utilizing docetaxel chemotherapy, setting a new standard of care for this disease. This paper examines the progress that has been made in HRPC with the Taxanes (Docetaxel, Paclitaxel, and Epothilones) with a glimpse on mechanisms of resistance and on combinations able to overcome it. In addition, new targeted therapies under development in combination with taxanes are reviewed with an explanation of their molecular mechanisms of action.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Current indications for chemotherapy in prostate cancer patients.

Recently, data from two randomized studies, TAX327 and SWOG 9916, which compared docetaxel-based chemotherapy to mitoxantrone-based therapy, have demonstrated that treatment with docetaxel can prolong life in a statistically significant way in patients with hormone refractory prostate cancer (HRPC). In the TAX237 trial the median overall survival rates for patients treated with docetaxel every 3 wk was 18.9 mo, compared with 16.4 mo for the patients in the control arm (p=0.009). Patients treated with the combination of docetaxel and estramustine in the SWOG trial had a significant improvement in median survival (18 mo vs 16 mo, p=0.01), longer progression-free survival (6 mo compared with 3 mo, p<0.0001), and a 20% reduction in the risk of death. The optimal timing of docetaxel-based chemotherapy is still unknown because there are no prospective clinical trials indicating whether earlier treatment is more effective than delayed treatment. There are now increasing options also for second-line therapies in the palliative treatment of HRPC, and ongoing studies on new drugs such as satraplatin and ixabepilone will define the role of these agents in this setting. Preliminary neoadjuvant and adjuvant chemotherapy studies in high-risk prostate cancer patients have demonstrated that these approaches are feasible and do not add morbidity to surgery or radiotherapy, but their impact on survival still needs to be proven in randomized studies.

Antineoplastic Agents↗
PubMed2006

Current therapies and advances in the treatment of pancreatic cancer.

Pancreatic cancer is a common, highly lethal disease with a rising incidence. In the last years continued efforts in pancreatic cancer research have led to a change in the classic approaches and to the development of new biological agents that appear to show promise. Adjuvant chemotherapy with gemcitabine has recently demonstrated better survival outcomes following surgical resection compared to no treatment, especially in patients with positive margins or lymph nodes. The addition of anti-VEGF agents to adjuvant regimens could improve long-term outcomes. In locally advanced disease, neoadjuvant regimens have not produced complete remissions, but partial responses have been reported ranging between 10 and 20%, with conflicting survival results. Combination trials with radiochemotherapy and new drugs appear well tolerated with encouraging preliminary results. In the metastatic setting, novel chemotherapeutic combinations and molecular targeted agents have shown promise in improving outcomes. To date, second line therapy is increasingly proposed and may even provide survival benefits in the future. This article summarizes the current standards of therapy for patients with resectable, advanced and metastatic pancreatic cancer.

Antimetabolites, Antineoplastic↗
PubMed2006

State-of-the-art management of metastatic disease at initial presentation or recurrence.

Carcinoma of the bladder is the second most prevalent genitourinay malignancy and the fifth most common solid tumor in the USA. On the basis of favorable response rates and survival data, cisplatin-based regimens can be considered the standard treatment for fit patients with metastatic urothelial cancer. Since cisplatin-containing regimens are contraindicated for patients with impaired renal function, gemcitabine plus either paclitaxel or docetaxel may be an effective and well-tolerated treatment option for these patients. Randomized trials are needed to determine the future role of these combinations in the management of advanced transitional cell carcinoma. The optimal regimens for the medically unfit patients and second-line chemotherapy remain undefined. Postchemotherapy surgical resection of residual cancer may result in a disease-free survival in highly selected patients who would otherwise die of the disease. Progresses in the understanding of the molecular biology of bladder cancer and identification of new targeted therapies will undoubtedly provide new opportunities but whether or not this approach to therapy will lead to better results must still be determined.

Antineoplastic Agents↗
PubMed2006

New treatment approaches in metastatic renal cell carcinoma.

PURPOSE OF REVIEW: Recent developments in the understanding of the molecular biology of renal cell carcinoma have led to the development of several biologic agents with different mechanisms of action. In 2005, promising results have been observed especially in second-line therapy following cytokine failures and in 2006 more mature data with regard to time to progression and overall survival should be available. This review, analyzing basic translational research principles, will summarize the available evidence with a glimpse of the future therapeutic approaches in renal cell carcinoma. RECENT FINDINGS: Vascular endothelial growth factor- and platelet-derived growth factor receptor-inhibiting drugs (SU11248, Bay 43-9006, Bevacizumab, AG-013736, etc.) report time to progression ranging between 4 and 9 months and variable benefits in overall survival. Confirmatory studies are ongoing regarding other novel treatments (CCI-779, Infliximab, PTK-787). SUMMARY: In renal cell carcinoma, there is a strong rationale for targeting multiple pathways and particularly angiogenesis. Vascular endothelial growth factor- and platelet-derived growth factor receptor-inhibiting drugs have been rapidly approved in the second-line setting and will soon be used as first-line therapy. In the next years, translational/clinical research will provide evidence for combination strategies to improve upon the results of the biologic agents and hopefully offer more hope to patients with renal cell carcinoma.

Angiogenesis Inhibitors↗
PubMed2005

Management of advanced prostate cancer after first-line chemotherapy.

Hormone refractory prostate cancer (HRPC) causes substantial morbidity and mortality. There are increasing options for both first- and second-line therapy in the palliative treatment of patients with HRPC. Medications to control symptoms should first be optimized in patients with late-stage disease, and radiotherapy applied to dominant painful bone lesions. Docetaxel, mitoxantrone, satraplatin, and ixabepilone are active chemotherapeutic agents in the first- and/or second-line setting for patients with HRPC, and this may be true also of older drugs such as oral cyclophosphamide and vinorelbine. Radioisotopes such as strontium and samarium are useful for treatment of more generalized bone pain. Third-line hormonal maneuvers including glucocorticoids, ketoconazole, and estrogens can lead to further palliation in some patients, and there are provocative data that chemotherapy might restore hormonal sensitivity in a subset of patients.

Antineoplastic Agents↗
PubMed2005

Colorectal cancer and antiangiogenic therapy: what can be expected in clinical practice?

Angiogenesis is a strongly regulated process, which is dependent upon a complex interplay between inhibitory and stimulatory angiogenic factors. It is essential for tumor growth and metastasis: increased angiogenesis is correlated with poor prognosis in cancer patients. Many novel compounds that potently inhibit formation of neoplastic blood vessels have been recently developed. Major categories of angiogenesis antagonists include protease inhibitors, direct inhibitors of endothelial cell proliferation and migration, angiogenic growth factor suppressors, inhibitors of endothelial-specific integrin/survival signalling, copper chelators, and inhibitors with other specific mechanisms. There is increasing interest in developing angio-suppressive agents for colorectal cancer treatment. Some 20 direct and indirect antiangiogenesis drugs are currently being evaluated in clinical trials in colorectal cancer (CRC). Promising results have been reported. These include an increase in overall survival and reduction in the risk of death (Bevacizumab), reversal of cellular resistance (Cetuximab) and activity as second-line therapy in patients who have exhausted other available treatment options (Cetuximab, ABX-EGF, PTK-787, Gefitinib, Erlotinib). This review will outline the mechanisms of action of the principal antiangiogenic drugs, summarize the available data on the use of these new drugs in colorectal cancer, discuss their impact in clinical practice and offer a glimpse into how antiangiogenetic therapy will be integrated into the future care of patients with gastrointestinal cancers.

Angiogenesis Inhibitors↗
PubMed2005

Chemotherapy for local treatment of bladder cancer.

This review documents the evidence that combination chemotherapy, known to be useful in metastatic disease, offers an advantage in the context of apparently localized disease. The use of neoadjuvant chemotherapy before cystectomy shows that pathologic complete responses can be obtained one-third of the time and that this, in combination with an aggressive TURBT, can be one strategy to preserve the bladder. The response to chemotherapy strongly predicts ultimate survival whatever the local therapy. Two recently updated randomized trials raise the possibility that neoadjuvant chemotherapy has a small but detectable survival benefit yet its use is controversial in everyday practice because of the desire of surgeons to perform an immediate cystectomy. The role of adjuvant chemotherapy remains undefined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Adjuvant chemotherapy for bladder cancer.

Radical cystectomy is a standard treatment for patients with muscle-invasive bladder cancer. The presence of occult micrometastatic disease is responsible for both local and distant failure after radical surgery. Postoperative administration of chemotherapy in bladder cancer patients can theoretically give the same survival advantage demonstrated in patients with breast and colon cancer. Studies evaluating adjuvant chemotherapy in patients with pT3-pT4 and/or pN+ M0 disease have major deficiencies in terms of sample sizes, early stopping of patient entry, statistical analyses, reporting of results and drawing conclusions. A recent meta-analysis including all previously published randomized trials concludes that, currently, there is insufficient evidence to reliably recommend adjuvant chemotherapy. The results of appropriately sized randomized trials are needed before any definitive conclusions can be drawn.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

New treatments for metastatic kidney cancer.

Renal cell carcinoma accounts for approximately 3% of adult malignancies and 90%-95% of neoplasms arising from the kidney. It is characterized by a lack of early warning signs, diverse clinical manifestations, resistance to radiation and chemotherapy, and infrequent but reproducible responses to immunotherapy with agents such as interferon alpha (IFNa) and interleukin 2 (IL-2). International studies have shown objective response rates of < 15% in patients with advanced and metastatic disease, with 5-year disease-specific survival ranging between 0-20%. Considering these poor outcomes, renal cancers' very vascular nature and overexpression of receptors for vascular endothelial growth factor (VEGF), various biologic and angio-suppressive therapies are being evaluated in clinical trials. Promising results in terms of overall response rate and median time to progression have been reported especially as second-line therapy following cytokine failure, a setting where no effective systemic therapy has been recognized (SU011248, Bay 43-9006, Bevacizumab and Erlotinib). While confirmatory studies are ongoing, other novel treatments in first line trials (CCI-779, Infliximab, PTK-787, and Thalidomide) have drawn international attention. This review, analyzing basic translational research principles, will summarize the available data on the use of these new therapeutic approaches in RCC.

Adult↗
PubMed2004

Development of and clinical experience with capecitabine (Xeloda) in the treatment of solid tumours.

The oral fluoropyrimidine capecitabine (Xeloda) delivers 5-FU to the tumour site, thereby limiting the side effects and other complications associated with intravenous (i.v.) 5-FU. As an oral drug, capecitabine is preferred to 5-FU by many patients as it can be conveniently taken at home. In first-line metastatic colorectal cancer (MCRC), capecitabine results in superior response rates and equivalent progression-free and overall survival compared with i.v. 5-FU/LV. There is also increasing evidence for replacing i.v. 5-FU with capecitabine in combination with other anticancer agents (e.g. oxaliplatin and irinotecan) in MCRC and in the adjuvant treatment of early stage colon cancer. In anthracycline-pretreated metastatic breast cancer (MBC), adding capecitabine to docetaxel improves survival, time to progression (TTP) and response rates beyond docetaxel. Single-agent capecitabine is also effective in pretreated MBC and is a promising first-line therapy. Capecitabine has a favourable safety profile, the most frequent adverse events being hand-foot syndrome, stomatitis and diarrhoea. Because capecitabine is orally administered, it is possible to intervene promptly with dose interruption/reduction to resolve adverse events without impacting on efficacy. The increasing availability of capecitabine in the home-based setting requires careful consideration of the role of the oncology nurse, who is the key link between the patient and clinician for effective and efficient management.

Administration, Oral↗