TUMORS OF THE URINARY SYSTEM
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Failure of cytotoxic chemotherapy, 1983-1988, and the emerging role of monoclonal antibodies for renal cancer.
Yagoda A; Bander NH.
Urol Int, 44(6):338-45 1989.This study evaluated the activity of 36 chemotherapy drugs used on 1,900 patients with kidney cancer between 1983 and 1988, and found that the overall anti-cancer activity of all drugs was less than 5-10%.
Systemic therapy for renal cell carcinoma.
Motzer RJ, Russo P.
J Urol 2000 Feb;163(2):408-17.This study reviewed the available literature published from 1990 to 1998 on the effects of systemic therapy in patients with kidney cancer. No significant survival benefits were observed in patients treated with single-dose chemotherapy. Immunotherapy with interferon-alpha and interleukin (IL)-2 produced response rates (tumor shrinkage) of only 10-20%. The results of three trials showed no benefits in terms of survival in patients treated with interferon-alpha after surgical kidney cancer resection, compared to those who received surgery only. The results of this study indicate that kidney cancer is highly refractory to current systemic treatment modalities.
Analysis of trials using chemotherapy for metastatic bladder cancer.
Tannock IF.
Prog Clin Biol Res, 260():487-98 1988.This article emphasizes that there is no conclusive evidence demonstrating that aggressive treatment regimens of chemotherapy in patients with diffuse bladder cancer are superior to less toxic ones.
Chemotherapy for renal cell carcinoma.
Hartmann JT, Bokemeyer C.
Anticancer Res 1999 Mar-Apr;19(2C):1541-3.This article emphasizes that chemotherapy has not been shown to clearly prolong survival in patients with kidney cancer and therefore has a limited role in the management of this disease.
Interferon-alpha and 5-fluorouracil therapy in patients with metastatic renal cell cancer: an open multicenter trial
The Japanese Study Group Against Renal Cancer.
Igarashi T, et al.
Urology, 53(1):53-9 1999 Jan.This study was conducted to further evaluate the role of the anti-cancer drug 5-fluorouracil in the management of patients with diffuse kidney cancer. Patients who received 5-fluorouracil in addition to interferon-alpha fared no better than those who received interpheron-alpha alone. This study does not confirm previous clinical trials demonstrating a positive effect derived from use of 5-fluorouracil.
A phase II study of high-dose cimetidine and the combination 5-fluorouracil, interferon alpha-2A, and leucovorin in advanced renal cell adenocarcinoma.
Creagan ET; et al.
Am J Clin Oncol, 21(5):475-8 1998 Oct.
This study evaluated the effects of the drugs cimetidine and leucovorin on survival in patients with advanced kidney cancer. Among the 31 patients who received cimetidine, only one partial tumor response (tumor shrinkage) was observed, and among the 31 who received leucovorin followed by a combination regimen of 5-fluorouracil and interferon-alpha, only two partial responses were observed. These results indicate that both regimens are ineffective in patients with advanced kidney cancer
Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma.
Groupe Francais d'Immunotherapie.
Negrier S. et al.
N Engl J Med 1998 Apr 30;338(18):1272-8.This study evaluated the effects on tumor response, relapse-free and overall survival in patients with kidney cancer treated with interleukin-2, interferon-alpha, or a combination of both. Although rates of tumor responses and relapse-free survival were higher in patients treated with both cytokines, overall survival did not differ between the three groups. The improved tumor response and time to progression of disease in patients receiving combination cytokines must be weighted against the increase in toxicity associated with such regimen, particularly taking in account the lack of effect on overall survival.
Survival in renal cell carcinoma-a randomized evaluation of tamoxifen vs interleukin 2, alpha-interferon (leucocyte) and tamoxifen.
Henriksson R, et al.
Br J Cancer 1998 Apr;77(8):1311-7.This study compared the effects of two treatment regimens, tamoxifen only or tamoxifen plus interleukin 2 and interferon-alpha, in a sample population of 128 patients with advanced stage kidney cancer. The cytokines interleukin 2 and interferon-alpha represent the best available current treatment for kidney cancer. Tamoxifen has been shown to enhance the anti-cancer activity of these cytokines, and is a relatively non-toxic drug. Sixty-three patients were randomized to receive tamoxifen only, and 65 were randomized to receive tamoxifen with the addition of interleukin 2 and interferon-alpha. Average time of follow-up was 11 months (0.4-48 months). No differences in survival could be observed between the two treatment groups. Complication rates were significantly higher in patients receiving combination treatment. Costs associated with both treatments varied considerably, from $360 per patient receiving tamoxifen only, to $27,000 per patients receiving combination treatment. Since treatment with interleukin 2 and interferon-alpha results in higher rates of adverse reactions and higher costs without being associated with improved survival, its utilization as routine treatment in patients with advanced kidney cancer is seriously questioned.
Interferon-alpha and 5-fluorouracil therapy in patients with metastatic renal cell cancer: an open multicenter trial.
The Japanese Study Group Against Renal Cancer.
Igarashi T, et al.
Urology 1999 Jan;53(1):53-9.This study evaluated the efficacy of a regimen consisting of 5-fluorouracil and interferon-alpha in the management of patients with advanced kidney cancer. The study was initiated after several clinical trials reported promising results with the use of the above combination regimen in this condition. Sixty-three patients were enrolled. Rates of tumor responses were no different from those reported in patients treated with interferon-alpha only. Survival rates appeared prolonged in patients undergoing combination treatment, but the improvement was deemed attributable to the better performance status of the patients enrolled in the trial. The authors concluded that this regimen is of limited value in the management of patients with kidney cancer.
Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up.
Minasian LM, Motzer RJ, Gluck L, Mazumdar M, Vlamis V, Krown SE.
J Clin Oncol 1993 Jul;11(7):1368-75.This study investigated the effects of treatment with interferon-alpha in152 patients with advanced stage kidney cancer. Overall rate of tumor response was 10%. Average duration of response was 12 months. The authors concluded that interferon-alpha has minimal activity in patients with advanced kidney cancer and new treatment options should be investigated.
Adjuvant immunotherapy in renal cell carcinoma--comparison of interferon alpha treatment with an untreated control.
Basting R, Corvin S, Handel D, Hinke A, Schmidt D.
Anticancer Res 1999 Mar-Apr;19(2C):1545-8.This study evaluated the impact of interferon-alpha on survival in patients with kidney cancer. One hundred twenty-five patients who underwent surgery for non-metastatic kidney cancer were evaluated; 33 of them had received interferon- alpha for 1 year. No differences in survival were observed between the two treatments groups, indicating that interferon-alpha is ineffective in patients with kidney cancer.
Subcutaneous interleukin-2, interferon alfa-2a, and continuous infusion of fluorouracil in metastatic renal cell carcinoma: a multicenter phase II trial.
Groupe Francais d'Immunotherapie.
Ravaud A, et al.
J Clin Oncol 1998 Aug;16(8):2728-32.This study evaluated the efficacy of treatment with interleukin-2, interferon alfa-2a, and fluorouracil in 111 patients with advanced kidney cancer. Only 2 partial tumor responses were observed, indicating that this regimen is ineffective in this cancer population.
Outpatient treatment with subcutaneous interleukin-2 and interferon alfa administration in combination with fluorouracil in patients with metastatic renal cell carcinoma
Results of a sequential nonrandomized phase II study. Subcutaneous Administration Propeukin Program Cooperative Group.
Tourani JM, et al.
J Clin Oncol 1998 Jul;16(7):2505-13.This study evaluated the efficacy of a combination protocol consisting of interleukin-2, interferon alfa-2a, and 5-fluorouracil in patients with advanced kidney cancer. The trial was stopped after analysis of preliminary data on 62 patients revealed a lack of benefit associated with treatment. Partial tumor shrinkage was observed in 19% of patients; however, only one was a complete remission. Severe toxicity occurred in 43% of patients. Survival rates were similar to those reported in patients treated with interleukin-2 only. The results of this study contradict a previous report indicating a beneficial effect associated with use of this protocol in patients with advanced kidney cancer.
Combined levamisole with recombinant interleukin-2 (IL-2) in patients with advanced renal cell carcinoma: a phase II study.
Creagan ET, et al.
Am J Clin Oncol 1998 Apr;21(2):139-41.This study evaluated the effectiveness or a regimen consisting of levamisole and interleukin-2 in 22 patients with advanced kidney cancer. Only one tumor response was observed, and it was partial. Treatment failure occurred after an average of 36 days, and was due to patient refusal, progression of disease, or interruption of treatment because of toxicity. These results indicate that combination regimen with levamisole and interleukin-2 is ineffective in patients with kidney cancer.
Multi-institutional study of the angiogenesis inhibitor TNP-470 in metastatic renal carcinoma.
Stadler WM, Kuzel T, Shapiro C, Sosman J, Clark J, Vogelzang NJ.
J Clin Oncol 1999 Aug;17(8):2541-5.This study evaluated the effects of treatment with TNP-470, a compound that inhibits the growth of capillary blood vessels, in 33 patients with advanced kidney cancer. Only one partial response was observed, and was of short duration. Side effects of treatment included: lack of energy, fatigue, vertigo, dizziness, loss of sense of balance and loss of concentration, and led to interruption of treatment in 5 patients.
Interferon Gamma-1b Compared with Placebo in Metastatic Renal-Cell Carcinoma.
Gleave, ME, et al.
New England Journal of Medicine, April 30, 1998 -- Vol. 338, No. 18.This was a randomized study conducted to evaluate the efficacy of treatment with interferon gamma-1b in patients with advanced kidney cancer. One hundred eighty-one patients were enrolled, and were randomly assigned to receive either interferon gamma-1b or placebo. No significant differences in tumor responses, time to progression of disease and overall survival were observed between the two groups. Tumor responses were 4.4% in patients receiving interferon, and 6.6% in those receiving placebo, and overall survival was 12.2 months in patients taking interferon and 15.7 months in those taking placebo. The results of this study show that immunotherapy with interferon gamma-1b is ineffective in patients with kidney cancer. This study does not support the results of previous uncontrolled trials indicating a beneficial effect associated with use of this regimen. Trials that don't use a control arm are subjected to selection bias, and their results should be confirmed in randomized studies before definite conclusions can be drawn.
Recombinant beta-interferon in the treatment of patients with metastatic renal cell carcinoma.
Mani S; Todd M; Poo WJ.
Am J Clin Oncol, 19(2):187-9 1996 Apr.This study evaluated the effects of recombinant beta-interferon in the management of 15 patients with diffuse kidney cancer. No tumor regression was observed. Treatment-related cardiovascular complications led to interruption of treatment in 3 patients (20%). Other side effects included mental status change requiring cessation of drug in 6.7% of cases, severe headache and muscle pains in 30% of patients, fatigue in approximately 50% of patients, diarrhea, nausea and vomiting, persistent fever and visual disturbance.
Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor
A report from the National Wilms' Tumor Study Group.
Green DM, et al.
J Clin Oncol 1998 Dec;16(12):3744-51.The results of this study show that children aged younger than 16 treated with 6 months of chemotherapy for kidney cancer fared as good in terms of survival, as those treated with chemotherapy for a 15-month period. The study was conducted on 905 children with Wilm's tumor (the most common type of kidney cancer in children and a rare form of cancer in the adults), enrolled from 1986 to 1994 in the trial. All children received a 6-month course of chemotherapy. After that, they were randomized to either no further treatment, or to continue with 9 additional months of chemotherapy. No differences in efficacy between the two protocols could be detected. The costs associated with long treatment were twice as high as those associated with short treatment.
Advanced transitional cell carcinoma of the upper urinary tract: patterns of failure, survival and impact of postoperative adjuvant radiotherapy.
Hall MC, Womack JS, Roehrborn CG, Carmody T, Sagalowsky AI.
J Urol 1998 Sep;160(3 Pt 1):703-6.The results of this study show that radiation therapy administered after surgery does not improve survival in patients with advanced cancer of the upper urinary tract.
Postoperative radiation therapy in 26 patients with invasive transitional cell carcinoma of the upper urinary tract: no impact on survival?
Maulard-Durdux C, et al.
J Urol 1996 Jan;155(1):115-7.The results of this study indicate that radiation therapy given after surgery does not improve the outcome of patients with advanced stage cancer of the upper urinary tract.
High risk of vascular events in patients with urothelial transitional cell carcinoma treated with cisplatin based chemotherapy.
Czaykowski PM; Moore MJ; Tannock IF.
J Urol, 160(6 Pt 1):2021-4 1998 Dec.This study shows that patients with cancer of the urinary tract who receive chemotherapy regimens containing cisplatin are at high risk of developing treatment-derived deep venous thrombosis and pulmonary embolism. In particular, 13% of patients undergoing cisplatin-based chemotherapy developed vascular complications, leading to substantial morbidity, longer hospital stay, and in approximately 10% of cases, death.
A randomized trial of cisplatin versus cisplatin plus methotrexate in advanced cancer of the urothelial tract.
Hillcoat BL; et al.
J Clin Oncol, 7(6):706-9 1989 Jun.The results of this study show that the addition of methotrexate to cisplatin in the treatment of advanced-stage cancer of the urinary tract, while prolonging the time to disease progression, has no significant effect on overall survival and is associated with significant toxicity.
Neo-adjuvant and adjuvant treatment of locally invasive bladder cancer.
Schultz-Lampel D, Lampel A.
Curr Opin Urol 1999 Sep;9(5):419-24.This article highlights that in spite of the fact that bladder cancer is very sensitive to chemotherapy and local tumor responses can be observed in up to 70% of patients, more than 20 years of research failed to conclude that chemotherapy administered before or after local treatment is associated with an undisputed survival advantage in patients with advanced bladder cancer. The authors conclude that chemotherapy cannot be routinely recommended in the management of patients with locally invasive bladder cancer.
Role of adjuvant chemotherapy in the treatment of invasive carcinoma of the urinary bladder.
Dimopoulos MA, Moulopoulos LA.
J Clin Oncol 1998 Apr;16(4):1601-12.This article reviewed all the studies published during the past 20 years evaluating the role of chemotherapy in the management of patients with locally advanced bladder cancer. A clear conclusion as to whether chemotherapy improves survival in this patient population could not be drawn, since the studies results were biased by methodological and statistical problems. The authors conclude that chemotherapy cannot be recommended as gold standard treatment for patients with advanced bladder cancer.
Neo-adjuvant (pre-emptive) cisplatin therapy in invasive transitional cell carcinoma of the bladder.
Wallace DM, et al.
Br J Urol 1991 Jun;67(6):608-15.The results of this study indicate that chemotherapy is ineffective in the treatment of patients with locally advanced bladder cancer. The study combined the results of two randomized trials conducted on a total of 255 patients, where treatment with radiation therapy alone was compared to treatment with chemotherapy followed by radiotherapy. No significant differences in survival were observed between the two groups, but patients who did not receive chemotherapy fared slightly better than those who received it.
Adjuvant chemotherapy with doxorubicin (Adriamycin) and 5-fluorouracil in T3, NX, MO bladder cancer treated with radiotherapy.
Richards B; et al.
Br J Urol, 55(4):386-91 1983 Aug.The results of this study show that survival rates in patients with diffuse bladder cancer receiving chemotherapy and radiation therapy are no better than those of patients receiving radiation therapy alone.
Adjuvant chemotherapy in T3 carcinoma of the bladder. A prospective trial: preliminary report.
Shearer RJ; Chilvers CF; Bloom HJ; Bliss JM; Horwich A; Babiker A.
Br J Urol, 62(6):558-64 1988 Dec.The results of this study show that the addition of methotrexate to radiation therapy in patients with diffuse bladder cancer is not associated with prolonged survival.
Does neoadjuvant cisplatin-based chemotherapy improve the survival of patients with locally advanced bladder cancer?
A meta-analysis of individual patient data from randomized clinical trials. Advanced Bladder Cancer Overview Collaboration.
Br J Urol 1995 Feb;75(2):206-13.This study is a meta-analysis of four randomized trials, conducted to determine whether chemotherapy with cisplatin administered prior to local treatment (surgery or radiotherapy) improves survival in patients with locally advanced bladder cancer. From the analysis of data on 479 individuals it was shown that use of chemotherapy was associated with a 2% increased risk of death, compared to non-use. A trend toward a possible beneficial effect of chemotherapy was observed only in patients younger than 60 years of age. Since there is still no conclusive evidence that neoadjuvant chemotherapy with cisplatin improves survival in patients with advanced bladder cancer, its use should not be routinely recommended in this patient population.
Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer
A randomised controlled trial. International collaboration of trialists.
Lancet 1999 Aug 14;354(9178):533-40.This study evaluated the effects of chemotherapy administered before local treatment in patients with locally advanced bladder cancer. The study was conducted on 976 patients who were randomized to receive either local treatment only (consisting of radical surgery or radiotherapy), or chemotherapy prior to local treatment. One percent of patients died from chemotherapy-related complications, and 3.7% died from surgery-related complications. Patients who remained alive were followed up for an average of 4 years. Although there was a 5% improvement in 3-year survival in patients receiving chemotherapy compared to those who did not, this benefit was too small to indicate a clear advantage associated with chemotherapy. These data indicate that chemotherapy cannot be routinely recommended in patients with locally advanced bladder cancer because its use it is not associated with the minimum 10% survival improvement necessary to justify its use in routine practice.
Metastatic bladder cancer: advances in treatment.
Stadler WM, Kuzel TM, Raghavan D, Levine E, Vogelzang NJ, Roth B, Dorr FA.
Eur J Cancer, 33 Suppl 1():S23-6 1997 Jan.This review article highlights that the most commonly used treatment regimen for advanced-stage bladder cancer, combination chemotherapy with cisplatin, methotrexate, vinblastine and doxorubicin, has only limited effects on overall survival and is associated with significant toxicity.
Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy
Initial results of Radiation Therapy Oncology Group 89-03.
Shipley WU, et al.
J Clin Oncol 1998 Nov;16(11):3576-83.The results of this study, conducted on 123 patients with locally advanced bladder cancer, show that those who received chemotherapy before selective bladder preservation fared no better in terms of rates of tumor response, relapse-free and overall survival, than those who underwent selective bladder preservation only.
Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation.
The National Cancer Institute of Canada Clinical Trials Group.
Coppin CM, et al.
J Clin Oncol 1996 Nov;14(11):2901-7.The results of this study show that the addition of cisplatin-based chemotherapy to radiation therapy in the management of patients with advanced bladder cancer does not reduce the occurrence of metastases nor prolongs survival. The study was conducted on 99 patients randomized to receive, before radical radiotherapy or pre-operative radiotherapy, either chemotherapy with cisplatin, or no treatment. No differences in the occurrence of metastases or in overall survival were observed between the two groups during a 6.5-year follow-up period.
Morbidity after preoperative radiotherapy and cystectomy in patients with bladder cancer.
Tomic R, Granfors T, Modig H.
Scand J Urol Nephrol 1997 Apr;31(2):149-53.The results of this study show that treatment with radiation therapy and surgery in patients with advanced bladder cancer is associated with high rates of complications. The study was conducted on 103 patients who received radiotherapy before surgical bladder removal, and 18 patients who received full dose radiotherapy followed by salvage surgery. Treatment-related complications occurred in 71% of patients receiving preoperative radiotherapy and 78% of those receiving full-dose radiotherapy. Intestinal complications occurred in 39% and 67% of patients treated with preoperative and full-dose radiotherapy, respectively, and were associated with a 3.3% mortality rate. These results indicate that combination treatment with radiotherapy and surgery in patients with bladder cancer is associated with significant morbidity and mortality. Toxicity was found to be positively associated with the amount of radiation exposure.
Radiotherapy in bladder cancer.
Sengelov L, von der Maase H.
Radiother Oncol 1999 Jul;52(1):1-14.This review emphasizes that chemotherapy, although being associated with improved time to progression of disease has not been shown to increase overall survival or rates of distant metastases in patients with bladder cancer. Also, no benefits have been demonstrated by use of radiation therapy before surgery, compared to surgery alone. The value of radiation therapy is difficult to assess, because changes in treatment and bias in patients selection make comparisons of rates of survival unfeasible. However, acute toxicity has been consistently demonstrated in 50% to 75% of patients, and long-term toxicity in 10% to 20% of them.
Planned preoperative radiation therapy in muscle invasive bladder cancer; results of a meta-analysis.
Huncharek M, Muscat J, Geschwind JF.
Anticancer Res 1998 May-Jun;18(3B):1931-4.This study is a meta-analysis of 5 randomized trials conducted to determine whether radiation therapy administered before surgery improves rates of survival in patients with advanced bladder cancer. No differences in survival were observed between patients who received radiotherapy prior to surgery compared to those who received surgery alone. These results indicate that pre-operative radiotherapy has no role in the routine management of patients with advanced stage bladder cancer.
Treatment of advanced bladder cancer with combined preoperative irradiation and radical cystectomy versus radical cystectomy alone
A phase III intergroup study.
Smith JA Jr, et al.
J Urol 1997 Mar;157(3):805-7.The results of this study show that radiation therapy administered before surgery does not prolong survival in patients with advanced bladder cancer. The study was conducted on 140 patients who were randomized to undergo surgical removal of the bladder (cystectomy) only, or radiation therapy prior to bladder removal. Five-year from initial treatment, 53% of the patients who received surgery alone were alive, compared to 43% of those who received surgery plus radiation. These data indicate that radiation therapy is ineffective in prolonging survival in patients with advanced bladder cancer, and its use may be associated with harm.
Short-term moderate-dose pelvic radiotherapy of advanced bladder carcinoma. A questionnaire-based evaluation of its symptomatic effect.
Fossa SD, Hosbach G.
Acta Oncol 1991;30(6):735-8.The results of this study show that radiation therapy administered to patients with advanced bladder cancer with the scope of relieving pain and other disease-related symptoms did not result in improvement of urinary symptoms other than incontinence, and did not improve overall quality of life. The efficacy of other forms of palliative treatment should be investigated.
Long-term follow-up of a bladder carcinoma cohort: questionable value of radical radiotherapy.
Holmang S, Hedelin H, Borghede G, Johansson SL.
J Urol 1997 May;157(5):1642-6.
The results of this study, conducted on 74 patients with bladder cancer treated with radical radiotherapy, show that the procedure is associated with a high-rate of treatment-related mortality (10%), significant morbidity, and high rates of tumor relapses (84%). The authors question whether elderly patients may really benefit from such regimen.
