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Biomedical subjects

Cora N Sternberg

Publications and source records attributed to Cora N Sternberg.

28 records · Page 2Linked to original sources
PubMed2003

Gemcitabine, paclitaxel, pemetrexed and other newer agents in urothelial and kidney cancers.

Significant progress has been made in understanding the biology of urothelial and kidney cancers. Approaches to advanced urothelial cancer include dose intensification, reducing toxicity in unfit or elderly patients, doublet and triplet combination chemotherapy and sequential regimens. Promising new chemotherapeutic agents such as the epothilones, pemetrexed (Alimta), topoisomerase inhibitors and vinflunine act at different phases of the cell cycle and on folate metabolism. New agents that are combined with chemotherapy in urothelial cancer include the farnesyl transferase inhibitors and growth factors receptor inhibitors. Renal cell carcinoma (RCC) is particularly resistant to cytotoxic agents, although a gemcitabine/fluorinated pyrimidine combination may have modest but real clinical benefit. In metastatic RCC, new biologic and targeted therapies include anti-angiogenesis agents such as anti-vascular endothelial growth factor (VEGF) antibody and thalidomide, as well as toremifene, CCI-779 and allogeneic stem cell transplantation. Metastatic urothelial and renal cell cancers continue to be the clinical trial focus of many novel agents. The molecular biology of these diseases is being unravelled and as knowledge accumulates, our ability to target these cancers will continue to increase.

Angiogenesis Inhibitors↗
PubMed2003

Can patient selection for bladder preservation be based on response to chemotherapy?

BACKGROUND: Neoadjuvant chemotherapy for patients with muscle-invasive bladder carcinoma is given to treat micrometastases and to preserve the bladder. The objective of this study was to evaluate the possibility of bladder preservation in patients with muscle-invasive bladder carcinoma who were treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy. METHODS: One hundred four consecutive patients with T2-T4,N0,M0 transitional cell carcinoma of the bladder were treated with 3 cycles of neoadjuvant M-VAC chemotherapy. After clinical restaging, 52 patients underwent transurethral resection of the bladder (TURB) alone, 13 patients underwent partial cystectomy, and 39 patients underwent radical cystectomy. RESULTS: The median survival for the entire group was 7.49 years (95% confidence interval, 4.86-10.0 years). Forty-nine patients (49%) were T0 at the time of TURB after receiving M-VAC. Thirty-one of 52 patients (60%) who received chemotherapy and underwent TURB alone were alive at a median follow-up of 56 + months (range, 10-160 + months): Twenty-three patients (44%) in that TURB group maintained an intact bladder. Of 13 responding patients with monofocal lesions who underwent partial cystectomy, only 1 patient required salvage cystectomy, and survival generally was good. The 5-year survival rate for this group was 69%. With a long median follow-up of 88 + months (range, 16-158 months), 4 patients (31%) were alive with a functioning bladder. In the radical cystectomy group, the median follow-up was 45 months (range, 4-172 + months), and 15 of 39 patients (38%) patients remained alive. In 77 patients who had their tumors down-staged to T0 or superficial disease, the median follow-up was 63 months (range, 4-172 + months), and the 5-year rate survival was 69%. This is in contrast to a 5-year survival rate of only 26% in 27 patients who failed to respond and had a status >/= T2 after receiving chemotherapy (median follow-up, 31 months; range, 7-156 + months). The median survival for 27 elderly patients (age >/= 70 years; median age, 73 years; range, 70-82 years) was 90 months (7.5 years). For elderly patients who underwent TURB and partial cystectomy, the 5-year survival rate was 67% with a 109-month (9-year) median survival; 47% of patients preserved their bladders intact. The median follow-up of the living elderly patients was 61 months (range, 20-120 + months). CONCLUSIONS: Bladder sparing in selected patients on the basis of response to neoadjuvant chemotherapy is a feasible approach that should be confirmed in prospective, randomized trials. Selected elderly patients are candidates for this approach.

Adult↗
PubMed2002

New drugs and new approaches for the treatment of metastatic urothelial cancer.

The median survival of patients with metastatic bladder cancer treated with M-VAC is approximately 1 year and long-term survival occurs in a small proportion of patients. Recent efforts to improve the outcome of patients with metastatic transitional cell carcinoma have focused on identifying new drugs with single agent activity and on their incorporation into platinum-based combination regimens. Paclitaxel, docetaxel, ifosfamide and gemcitabine are among the most active new agents. A large number of phase I-II trials have evaluated these agents in two- and three-drug combination regimens. The response proportion observed with these combinations varies considerably and median survival times range from 8 to 20 months. A better understanding of the molecular biology of bladder cancer will undoubtedly influence the selection of new therapeutic modalities. Molecular targeted small molecule therapy and monoclonal antibodies have begun to dominate contemporary studies. Whether or not this approach to therapy will lead to better results must still be determined.

Antimetabolites, Antineoplastic↗
PubMed2002

Localized and locally advanced bladder cancer.

Localized and locally advanced bladder cancer represents a heterogeneous spectrum of diseases with different biologic and clinical behavior. It varies with respect to invasive potential, propensity for metastases, and sensitivity to chemotherapy. Although several significant surgical advances have been made over the past 20 years in the treatment of muscle-invasive bladder cancer, resulting in decreases in perioperative morbidity and mortality and improvement of quality of life in patients with continent urinary diversions, the natural history of the disease has remained unaltered. Advances in chemotherapy for metastatic disease have prompted trials of systemic therapy in patients with early stage, high-risk disease administered before or after local therapy consisting of cystectomy or radiotherapy. The data available from nonrandomized and randomized trials have not definitively established the exact role of neoadjuvant chemotherapy and its impact on survival. Even if neoadjuvant chemotherapy does not improve survival, preliminary data suggest that bladder preservation may be possible in selected patients and that such combined therapy will hopefully lead to better patient management. The trials of postoperative chemotherapy provide insufficient evidence to support the routine use of adjuvant chemotherapy in clinical practice as a result of small sample size, confusing analyses, and the reporting of questionable conclusions. New large-scale, multicenter trials are imperative to provide convincing results. A better understanding of the microbiology of bladder cancer will influence the search for new therapeutic modalities. Molecular-targeted small-molecule therapy and monoclonal antibodies have begun to dominate contemporary studies.

Chemotherapy, Adjuvant↗
PubMed2002

Long-term follow-up of G3T1 transitional cell carcinoma of the bladder treated with intravesical bacille Calmette-Guérin: 18-year experience.

OBJECTIVES: Immunotherapy with bacille Calmette-Guérin (BCG) has been proposed in the past decade as first-line treatment for high-grade superficial bladder cancer (G3T1). We report our 18-year experience in the treatment of patients with G3T1 bladder cancer. METHODS: From January 1989 to July 1997, 670 patients underwent transurethral resection for superficial bladder cancer. Eighty-one patients (12%) had G3T1 tumors. All of these patients were treated with an innovative schedule of Pasteur strain BCG followed by maintenance BCG therapy. Treatment consisted of four cycles of 6 instillations per cycle of BCG. The first cycle was administered weekly x 6, the second was given every 2 weeks x 6, the third cycle was given monthly x 6, and the fourth was given every 3 months x 6 instillations. RESULTS: Sixty-nine patients (84%) completed at least the first two cycles. At a median follow-up of 76 months (range 30 to 197), the overall recurrence rate was 33% (27 of 81). The median time to recurrence was 20 months (range 5 to 128). Of these patients, 12 (15%) had progression at a median follow-up of 16 months (range 8 to 58). Cystectomy was required in 7 patients (8%). Death from disease occurred in 5 (6%) of 81 patients. One patient died of adenocarcinoma at the ureterosigmoidostomy site. Sixty patients (74%) were alive at a median follow-up of 79+ months (range 15 to 182). Of these, 56 (69%) were alive with a functioning bladder. CONCLUSIONS: Conservative treatment with BCG is a reasonable approach for patients with primary G3T1 transitional cell carcinoma of the bladder. The long-term results of BCG therapy are good. Cystectomy may not be justified as the therapy of choice in first-line treatment of high-grade superficial carcinoma of the bladder.

Adjuvants, Immunologic↗
PubMed2002

Bladder cancer.

Bladder cancer is the second most frequent tumour of the urogenital tract. Tobacco smoke has been shown to increase the risk of bladder cancer two- to fivefold as well as the exposure to metabolites of aniline dyes and other aromatic amines. Seventy-five per cent of bladder cancers are superficial at initial presentation, limited to the mucosa, submucosa, or lamina propria. Recurrence rates after initial treatment are 50-80%, with progression to muscle-invading tumour in 10-25%. In muscle-invading bladder cancers, there is a 50% risk of distant metastases. Surgery is the mainstay of standard treatment both in the form of transurethral endoscopic resection, mainly for superficial disease, and in the form of open ablative surgery with urinary diversion for muscle invasive disease. Endovesical administration of BCG has been employed after endoscopic resection as the most effective agent for both prophylaxis of disease recurrence and progression from superficial to invasive disease. The accepted treatment for muscle infiltrative disease is radical cystectomy. Response rates to combination chemotherapy regimens of up to 70% in patients with advanced metastatic disease have led to an investigation of its use for locally invasive disease in combination with conventional modalities of treatment.

Antineoplastic Agents↗
PubMed2002

Highlights of contemporary issues in the medical management of prostate cancer.

This paper highlights contemporary issues in the medical management of prostate cancer. Controversies surrounding adjuvant and neo-adjuvant hormonal therapy in localized prostate cancer are reviewed, as well as the use of chemohormonal therapy in high risk localized disease. The latent period of asymptomatic biochemical progression prior to clinical progression is an opportunity to evaluate new non-toxic therapies. In patients with advanced metastatic disease hormonal therapy and new alternatives are discussed. Chemotherapy in hormone refractory prostate cancer (HRPC) is extensively covered as well as the emerging role of molecular-targeted therapies.

Antineoplastic Agents↗
PubMed2002

Overview of international collaborative group prostate cancer trials.

Clinical trials in prostate cancer have gained increasing influence upon the practice of medicine. A survey was conducted of ongoing International Collaborative Group Phase III trials in localized disease, high risk and locally advanced disease, post prostatectomy, rising PSA, metastatic disease, hormone refractory prostate cancer, chemoprevention, and screening. International cooperation has the advantage of faster recruitment of patients in order to more quickly answer important scientific questions. True international collaboration can avoid duplication of efforts and promote mutual planning of trials. It is essential to treat patients with prostate cancer in the framework of clinical trials since there are still many unanswered questions.

Antineoplastic Agents, Hormonal↗
PubMed2002

High-risk metastatic urothelial cancer: chances for cure?

The median survival of patients with metastatic bladder cancer treated with methotrexate, vinblastine, adriamycin, and cisplatin chemotherapy is approximately 1 year and long-term survival occurs in a small proportion of patients. Recent efforts to improve the outcome of patients with metastatic transitional cell carcinoma have focused on the identification of new drugs with single agent activity and on their incorporation into platinum-based combination regimens. Paclitaxel, docetaxel, ifosfamide and gemcitabine are among the most active new agents. A large number of phase I/II trials have evaluated these agents in two- and three-drug combination regimens. The response proportion observed with these combinations varies considerably and median survival times range from 8 to 20 months. Because it is known that pretreatment prognostic features have an impact on individual patient outcome, the variation in reported survival in patients treated with chemotherapy may be a consequence of pretreatment patient characteristics. The role of surgery in metastatic bladder cancer is still controversial. After a significant response to chemotherapy, resection of residual resistant disease may be performed with intent to cure in highly selected patients. As obtainment of complete remission is a prerequisite for long-term survival, new therapeutic strategies, such as molecular targeted small molecule therapy and monoclonal antibodies, and new molecular markers predictive of response have the potential to be incorporated into the current treatment strategies, increasing the rate of cure.

Carcinoma, Transitional Cell↗