Journal of Clinical Oncology, Vol 20, Issue 1
(January), 2002: 289-296
© 2002 American Society for Clinical Oncology
Interferon-Alfa as a Comparative Treatment for Clinical Trials of New Therapies Against Advanced Renal Cell Carcinoma
By Robert J. Motzer,
Jennifer Bacik,
Barbara A. Murphy,
Paul Russo,
Madhu Mazumdar
From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, and Departments of Medicine, Epidemiology and Biostatistics, and Urology, Memorial Sloan-Kettering Cancer Center; and Department of Medicine, Cornell University Medical College, New York, NY; and Vanderbilt University, Nashville, TN.
Address reprint requests to Robert J. Motzer, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; email: motzerr{at}mskcc.org
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ABSTRACT
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PURPOSE: To define outcome data and prognostic criteria for patients with metastatic renal cell carcinoma (RCC) treated with interferon-alfa as initial systemic therapy. The data can be applied to design and interpretation of clinical trials of new agents and treatment programs against this refractory malignancy.
PATIENTS AND METHODS: Four hundred sixty-three patients with advanced RCC administered interferon- as first-line systemic therapy on six prospective clinical trials were the subjects of this retrospective analysis. Three risk categories for predicting survival were identified on the basis of five pretreatment clinical features by a stratified Cox proportional hazards model.
RESULTS: The median overall survival time was 13 months. The median time to progression was 4.7 months. Five variables were used as risk factors for short survival: low Karnofsky performance status, high lactate dehydrogenase, low serum hemoglobin, high corrected serum calcium, and time from initial RCC diagnosis to start of interferon- therapy of less than one year. Each patient was assigned to one of three risk groups: those with zero risk factors (favorable risk), those with one or two (intermediate risk), and those with three or more (poor risk). The median time to death of patients deemed favorable risk was 30 months. Median survival time in the intermediate-risk group was 14 months. In contrast, the poor-risk group had a median survival time of 5 months.
CONCLUSION: Progression-free and overall survival with interferon- treatment can be compared with new therapies in phase II and III clinical investigations. The prognostic model is suitable for risk stratification of phase III trials using interferon- as the comparative treatment arm.
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INTRODUCTION
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CLINICAL INVESTIGATION of new agents and combination regimens to identify more effective therapy are of the highest priority for patients with metastatic renal cell carcinoma (RCC).1-5 For this purpose, interferon-alfa can be considered a suitable treatment for comparison in phase II and phase III RCC clinical trials of promising new agents. Interferon- has a low but reproducible response proportion and relative tolerability and can be administered in the outpatient setting. A modest survival benefit for this therapy against metastatic RCC has been cited in two recent phase III trials that compared interferon- to vinblastine or medroxyprogesterone.6,7 Also, interferon- is a likely candidate for clinical trials in combination with novel agents, given the highly resistant nature of RCC against chemotherapy.
Determining prognostic factors of survival for patients with advanced RCC is valuable in designing and interpreting results of clinical trials. We have previously reported on a survival and prognostic stratification model derived from 670 patients treated in clinical trials of cytokine or chemotherapy at the Memorial Sloan-Kettering Cancer Center (MSKCC).8 Systemic treatment for patients in that series was varied, composed of interferon-, interleukin-2, hormones, and/or chemotherapy, and included patients who had received prior systemic therapy. In that series, we identified a relationship between prior nephrectomy (a risk factor used in the model) and time from initial diagnosis to treatment as prognostic factors for survival.9 Since that model was derived, two phase III randomized trials have reported a survival benefit for cytoreductive nephrectomy before interferon-.10,11 Therefore, the indication for nephrectomy has changed; it is likely that most patients with resectable primary tumors will undergo nephrectomy before cytokine therapy. In the study reported herein, 40% of patients were treated at centers other than MSKCC. We noticed variability in the normal values of the laboratory markers across treatment centers and adjusted our analysis accordingly.
The reduction of heterogeneity caused by various therapies and the assessment of the role of nephrectomy as a risk factor in the light of the randomized trial10 prompted this analysis. We report on outcome and prognostic factors for survival after interferon- therapy for 463 previously untreated patients. The outcome data and risk model can be applied to phase II and III clinical trial design, as well as interpretation of novel treatments against RCC.
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PATIENTS AND METHODS
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Four hundred sixty-three patients with advanced RCC who were treated with interferon- alone or as part of combination therapy were the subject of this retrospective analysis. All were treated on one of six institutional review board-approved clinical trials at the Memorial Sloan-Kettering Cancer Center (MSKCC) or as part of a multicenter trial coordinated by MSKCC.12-15 Patients from those studies were included in this analysis if they were assessable for survival and had not received prior systemic therapy, ie, the interferon-–containing clinical trial represented their first systemic treatment. Accrual for the clinical trials ranged from March 1982 to July 1996. The number of patients derived from each clinical trial, the period of accrual, and a summary of the treatment program are shown in Table 1. Eligibility, treatment programs, and results were reported for the individual trials.12-15
Eligibility criteria for all protocols included histologic confirmation of RCC; stage IV disease with measurable lesions; adequate Karnofsky performance status; lack of severe comorbid conditions; and adequate hematologic, renal, and hepatic function. Pretreatment patient characteristics, first date of treatment with interferon-, best response, date of progression, and date of death or last follow-up were recorded for all patients. Response and progression were defined by standard criteria.16
Survival Analysis
Survival time was defined as the time from initiation of treatment to the date of death or last follow-up. Survival distributions were estimated using Kaplan-Meier methodology.17 Clinical features examined in univariate survival analysis included number and sites of metastases (lung, mediastinum, bone, liver, retroperitoneum), Karnofsky performance status, prior radiation treatment, prior nephrectomy, the time interval from diagnosis to start of treatment, and the selected baseline biochemical features of hemoglobin, serum albumin, alkaline phosphatase, and lactate dehydrogenase (LDH). For each of these four laboratory markers, the normal value of the assay varied across the treatment centers (Table 2). Therefore, for each patient, we used the ratio of the measured value to normal value. The lower limit of normal was used for albumin and hemoglobin and the upper limit was used for LDH and alkaline phosphatase. We also considered corrected calcium concentration in the survival analysis. It was calculated using the formula corrected calcium = total calcium - 0.707[albumin - 3.4] to remove the effects of protein binding and to assess free calcium.
The relationship between survival and each of the variables was analyzed using the log-rank test18 for categorical variables and a score test based on the Cox proportional hazards model19 for continuous variables. There were few missing values for any of the variables (none larger than 4%), and in all analyses, case deletion was used to handle the missing values. When necessary, a logarithmic transformation was used to reduce skewness.
Multivariate Model
A significance level of 5% was used as the criterion for the inclusion of a variable in the stepwise modeling procedure. Because this retrospective study included patients in clinical trials from 1982 through 1996, two strata were defined according to when the patient received treatment (1982 to 1990, 1991 to 1996). The stratified Cox proportional hazards model20 states that the hazard or risk of death at time t for a patient in strata j with variables x = (x1j, x2j, ...., xpj) is
equation
where  0j(t) is the baseline hazard function for strata j and ß1, ß2, ..., ßp are the regression coefficients. Using a stepwise modeling algorithm with a .15 significance level for entering and removing explanatory variables, independent risk factors were determined, and the model was formed.
Dichotomization of the continuous variables identified in the model was performed using the minimum P-value approach.8,21 Using the categorical counterparts of the risk factors, each patient was then assigned to one of three risk groups: those with zero risk factors (favorable risk), those with one or two (intermediate risk), and those with three or more (poor risk). Survival curves for each of these groups were estimated, and the groups were compared using the log-rank test.
Validation of Model by Bootstrap Technique
The predictive performance of the model was internally validated through a two-step, nonparametric bootstrapping process.22 In the bootstrap procedure, the original set of data of size N becomes a parent population from which samples of size N are randomly drawn with replacement. In the first step of internal validation, the bootstrapping technique was used for variable selection. Two hundred bootstrap samples were created, and a stepwise procedure was applied to each sample using the same significance level for entering and removing a variable as in the original modeling. From this analysis, we calculated the percentage of samples for which each variable was included in the model from the 200 samples. Percent inclusion was used to determine the prognostic importance of a variable because it was expected that a prognostically important variable would be included in the model for a majority of the bootstrap samples. A model was formulated that contained the five variables with the greatest percent inclusion.23 Models obtained from the stepwise modeling algorithm and the bootstrapping technique were compared.
In the second internal validation step, the bootstrap was used for parameter estimation. Three hundred bootstrap samples were created, and for each of the samples, the model with the five final variables was refit, and the regression parameters and risk ratios were estimated. The sample mean and SDs of the 300 risk ratios for each parameter were computed and used to formulate confidence intervals (CIs) about the risk ratio. These estimates were compared with those quantities obtained in the final Cox model.
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RESULTS
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Patient Characteristics and Treatment
The median age was 59 years, and 66% were male (Table 3). Fifty-five percent had undergone prior nephrectomy, and 16% had received prior radiation therapy. Three hundred nineteen (69%) had an interval from initial diagnosis to initiation of treatment with interferon- of less than 1 year, and 144 (31%) had an interval from initial diagnosis to initiation of treatment of 1 year or greater. Sixty-one percent had two or more sites of metastases. Two hundred seventy-eight (60%) were treated at MSKCC, and 185 (40%) were treated elsewhere on an MSKCC trial. The overall response rate for the 463 patients was 11%, which included 12 complete responses and 41 partial responses.
Baseline Laboratory Parameters
The median of corrected calcium was 9.2, with a range of 6.2 to 12.4. The lower and upper limits of normal values for albumin, alkaline phosphatase, hemoglobin, and LDH varied across 80 centers (Table 2). For example, the lower limit of normal for albumin for one of the centers was 0.8 g/dL, and for another center it was 4.1 g/dL.
Overall and Progression-Free Survival Distribution
The median overall survival time was 13 months (95% CI, 12 to 15 months) (Fig 1). Sixty-one (13%) of the 463 patients remain alive, and the median follow-up time for survivors was 46 months (range, 1 to 181 months). The proportion of patients surviving at 1 year was 54%. The 2-year, 3-year, and 5-year survival proportions were 30%, 19%, and 10%, respectively.
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Fig 1. Survival time in 463 patients with advanced RCC treated with interferon-; 61 patients were alive at last follow-up, indicated by |.
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Fifty-seven patients remained progression-free after treatment with interferon- at last follow-up. The median progression-free survival time was 4.7 months (95% CI, 4.1 to 5.3 months) (Fig 2). The proportions of progression-free patients at 4, 6, 12, 24, and 36 months were 55%, 42%, 24%, 14%, and 8%, respectively.
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Fig 2. Progression-free survival in 463 patients with advanced RCC treated with interferon-; 57 remain progression-free at end of follow-up, indicated by |.
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Univariate Survival Analysis
Factors considered in the univariate survival analyses included number and site of metastases, prior nephrectomy, prior radiotherapy, Karnofsky performance status, and baseline biochemical parameters (Tables 4 and 5). Clinical features associated with an adverse prognosis included presence of hepatic metastasis, Karnofsky performance status less than 80%, lack of prior nephrectomy, and a time interval from disease diagnosis to treatment of less than 1 year.
The biochemical parameters found to be significant for an adverse prognosis included low serum albumin, elevated serum alkaline phosphatase, low hemoglobin, elevated serum LDH level, and a high corrected serum calcium level.
Multivariate Survival Analysis
The nine variables outlined above were included in the multivariate analysis. The five most significant risk factors that predicted survival were hemoglobin, LDH, corrected calcium, Karnofsky performance status, and interval from diagnosis to treatment. Liver metastases reached a marginal significance level (P = .02) and was not kept in the final model.
Risk Groups
Five risk factors were used to create the risk model: low Karnofsky performance status (< 80%), high LDH (> 1.5 times the upper limit of normal), low serum hemoglobin, high corrected serum calcium (> 10 mg/dL), and time from initial diagnosis to interferon- of less than 1 year. The cut-points for LDH and hemoglobin were found by the minimum P-value approach.8,21 A Cox model was fit using the categorical versions of the variables (Tables 6 and 7). Each patient was then assigned to one of three risk groups: those with zero risk factors (favorable risk), those with one or two (intermediate risk), and those with three or more (poor risk).
There was a significant difference in the survival profiles of the three risk groups (P < .0001) (Fig 3). The median survival time for the 18% of favorable-risk patients was 30 months, and the 1-year, 2-year, and 3-year survival rates were 83%, 55%, and 45%, respectively. Sixty-two percent of patients were in the intermediate-risk group, and the median survival time for this group was 14 months, with 1-year, 2-year, and 3-year survival rates of 58%, 31%, and 17%, respectively. The poor-risk group comprised 20% of patients and had a median survival of 5 months, with 1-year, 2-year, and 3-year survival rates of 20%, 6%, and 2%.
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Fig 3. Survival stratified according to risk group (N = 437); 26 patients who were missing one or more of the five risk factors were excluded. | indicates last follow-up.
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Progression-free survival for patients was calculated according to risk group. The median progression-free survival increased from 2.5 to 5.1 to 8.3 months in poor-risk, intermediate-risk, and favorable-risk groups, respectively (Table 8).
Bootstrap Validation
For the first step of validation, the five variables with the greatest percent inclusion were hemoglobin, LDH, corrected calcium, Karnofsky performance status, and time from diagnosis to treatment (Table9). The results of this model selection technique confirmed the variables chosen in the original modeling procedure. Of note, percent inclusion for the variable interval from diagnosis to treatment was 85%, compared with 29% for prior nephrectomy.
In the second step of validation for each covariate in the final model, a risk ratio with a 95% CI was estimated. Risk ratios were similar to those obtained in the original multivariate model (data not shown). The results of these two steps provide evidence of the robustness of the model-building process.
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DISCUSSION
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Interferon- and interleukin-2 show a low degree of antitumor effect against RCC.1,5 Outcome data from either cytokine may be considered in clinical trial design and interpretation of new therapies. Patients treated with high-dose bolus interleukin-2 have been reported to achieve durable responses.24 However, treatment-related toxicity can be severe, mandating stringent patient selection, intensive supportive care, and specialized treatment centers; therefore, its use as the comparative treatment arm in phase III trials limits both center and patient participation. Also, the patient population selected to tolerate the intensive therapy may differ from those deemed appropriate for the investigational therapy. In contrast, interferon- is administered as outpatient therapy and can be used in a less restricted patient population. Several recently reported phase III trials in advanced RCC used interferon- as the compared treatment arm.15,25-29
The determination of prognostic factors for survival in patients with advanced RCC is vital in designing and interpreting phase III randomized clinical trials. In this report, survival data and a model for assessing outcome and prognosis for patients treated with interferon- as first-line systemic therapy is provided. We have previously reported on a survival and prognostic stratification model derived from 670 patients treated in clinical trials of cytokine or chemotherapy at our center.8 The prognostic model based on first-line interferon- therapy included the same risk factors as the previously published model did,8 except the no-prior-nephrectomy risk factor was replaced with time from initial diagnosis to interferon- treatment of less than 1 year.
The role of cytoreductive nephrectomy for patients with stage IV RCC has been controversial.5 The longer survival time in patients after nephrectomy12 was predominantly linked with a long disease-free interval in patients who underwent surgical resection for a localized tumor and subsequently relapsed, which reflected a more indolent tumor biology when compared with survival of patients who presented de novo with a renal primary tumor and clinical evidence of metastases.9 Two recent randomized trials showed an improvement in survival for patients who undergo nephrectomy versus no surgery before treatment with interferon-.10,11 The improvement in survival was greatest for patients with high performance status and metastases confined to lung.10
On the basis of the results of these trials,10,11 selected patients with stage IV RCC will undergo nephrectomy before cytokine therapy. The indication for nephrectomy has changed in standard management from that used in the previously reported model,8 and it is likely that many more patients will undergo nephrectomy before interferon- (or other cytokine) therapy. Therefore, the substitution of time from initial RCC diagnosis to interferon- therapy for nephrectomy as a risk factor in our model is indicated.
Investigational therapies with immunotherapy, angiogenesis inhibition, or other novel treatment strategies could show an antitumor effect by producing prolonged stabilization of disease or slow tumor regression during many months.30 Therefore, phase II and III clinical trials of these agents against RCC may investigate progression-free survival as an end point of treatment outcome. The 4-month and 6-month progression-free survival rates associated with interferon- therapy were 55% and 42%, respectively. These rates can be used for designing future clinical trials of novel agents including angiogenesis inhibitors. Reporting of prognostic factors in phase II trials should be encouraged, as these factors help interpret outcome for a given patient population.
The outcome data from interferon- and the risk model derived from this study can be applied to the design and interpretation of phase II and III trials of new agents or combination programs against metastatic RCC. Several aspects of this analysis warrant comment and continued study. First, validation of the risk model was performed by the bootstrap method.22 Repeated sampling of the original data with replacement allowed independent samples of RCC patients to be generated from which the robustness of the model-building process was assessed. Validation of the model on an external data set would be useful.
Second, several prognostic models obtained by multivariate analyses in patients with metastatic RCC have been reported.31-36 These have been reviewed and compared with the MSKCC model.8 In this regard, a consensus on prognostic criteria for metastatic RCC is warranted. Third, recent progress in understanding of genetic features of RCC has facilitated classification into clear-cell and non–clear-cell subtypes (papillary, chromophobe, collecting duct).1 Specification of RCC histology into subtypes was not a part of this analysis. However, review of pathology of 109 patients treated at MSKCC with interferon- on the most recent trial15 included in this analysis identified eight patients (7%) with non–clear-cell histology (six chromophobe, two collecting duct). The relative sensitivity of RCC cell subtypes to interferon- remains to be determined.
In summary, the low proportion of patients with advanced RCC achieving long-term survival emphasizes the need for clinical investigation to identify more effective therapy. Progression-free and overall survival for interferon- treatment can be used as a baseline for assessment of new therapies in phase II and III clinical investigations. The prognostic model is suitable for risk stratification of phase III trials using interferon- as the comparative treatment arm and single-arm phase II trials to study progression-free survival as an end point.
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ACKNOWLEDGMENTS
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Supported in part by grant no. CA-05826 and K24 CA-82431 from the National Institutes of Health, Bethesda, MD.
We thank Carol Pearce for her review of the manuscript.
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REFERENCES
|
|---|
1.
Motzer RJ, Bander NH, Nanus DM: Renal cell carcinoma. N Engl J Med 335: 865-875, 1996[Free Full Text]
2.
Vogelzang NJ, Stadler WM: Kidney cancer. Lancet 352: 1691-1696, 1998[CrossRef][Medline]
3.
Bukowski R: Immunotherapy in renal cell carcinoma. Oncology 13: 801-813, 1999[Medline]
4.
Figlin RA: Renal cell carcinoma: Management of advanced disease. J Urol 161: 381-387, 1999[CrossRef][Medline]
5.
Motzer RJ, Russo P: Systemic therapy for renal cell carcinoma. J Urol 163: 408-417, 2000[CrossRef][Medline]
6.
Pyrhonen S, Salminen E, Ruutu M, et al: Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol 17: 2859-2867, 1999[Abstract/Free Full Text]
7.
Medical Research Council and Collaborators: Interferon-alpha and survival inmetastatic renal carcinoma: Early results of a randomised controlled trial. Lancet 353: 14-17, 1999[CrossRef][Medline]
8.
Motzer RJ, Mazumdar M, Bacik J, et al: Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17: 2530-2540, 1999[Abstract/Free Full Text]
9.
Motzer RJ, Mazumdar M, Bacik J, et al: Effect of cytokine therapy on survival for patients with advanced renal cell carcinoma. J Clin Oncol 18: 1928-1935, 1999[Abstract/Free Full Text]
10.
Flanigan RC, Blumenstein BA, Salmon S, et al: Cytoreduction nephrectomy in metastatic renal cancer: The results of the Southwest Oncology Group trial 8949. Proc Am Soc Clin Oncol 19: 2a, 2000 (abstr 3)
11.
Mickisch G, Garin MM, Madej L, et al: Tumor nephrectomy plus interferon alpha is superior to interferon alpha alone in metastatic renal cell carcinoma. J Urol 163: 176, 2001 (abstr)
12.
Minasian LM, Motzer RJ, Gluck L, et al: Interferon alfa-2a in advanced renal cell carcinoma: Treatment results and survival in 159 patients with long-term follow-up. J Clin Oncol 11: 1368-1375, 1993[Abstract/Free Full Text]
13.
Ilson DH, Motzer RJ, Kradin RL, et al: A phase II trial of interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma. J Clin Oncol 10: 1124-1130, 1992[Abstract]
14.
Motzer RJ, Schwartz L, Murray Law T, et al: Interferon alfa-2a and 13-cis-retinoic acid in renal cell carcinoma: Antitumor activity in a phase II trial and interactions in vitro. J Clin Oncol 13: 1950-1957, 1995[Abstract/Free Full Text]
15.
Motzer RJ, Murphy B, Bacik J, et al: Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma. J Clin Oncol 18: 2972-2980, 2000[Abstract/Free Full Text]
16.
Miller AB, Hoogstraten B, Staquet M, et al: Reporting results of cancer treatment. Cancer 47: 207-214, 1981[CrossRef][Medline]
17.
Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457-481, 1958[CrossRef]
18.
Mantel N: Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50: 163-170, 1966[Medline]
19.
Cox DR, Oakes D: Analysis of survival data (ed 1). New York, NY, Chapman and Hall, 1990
20.
Collet D: Modelling survival data in medical research. London, United Kingdom, Chapman and Hall, 1994
21.
Mazumdar M, Glassman J: Categorizing a prognostic variable: Review of methods, codes for easy implementation and application to decision-making about cancer treatments. Stat Med 19: 113-132, 2000[CrossRef][Medline]
22.
Chen CH, George SL: The bootstrap and identification of prognostic factors via Cox’s proportional hazards regression model. Stat Med 4: 39-46, 1985[Medline]
23.
Sauerbrei W, Schumacher M: A bootstrap resampling procedure for model building: Application to the Cox regression model. Stat Med 11: 2093-2109, 1992[Medline]
24.
Atkins MB, Dutcher JP: Renal-cell carcinoma. N Engl J Med 336: 809, 1997 (letter)[Free Full Text]
25.
Fossa SD, Martinelli G, Otto U, et al: Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: Results of a European multi-center phase III study. Ann Oncol 3: 301-305, 1992[Abstract/Free Full Text]
26.
Neidhart JA, Anderson SA, Harris JE, et al: Vinblastine fails to improve response of renal cancer to interferon alfa-n1: High response rate in patients with pulmonary metastases. J Clin Oncol 9: 832-836, 1991[Abstract]
27.
Negrier S, Escudier B, Lasset C, et al: Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. N Engl J Med 338: 1273-1278, 1998
28.
Sagaster P, Micksche M, Flamm J, et al: Randomised study using IFN-alpha plus coumarin and cimetidine for treatment of advanced renal cell cancer. Ann Oncol 6: 999-1003, 1995[Abstract/Free Full Text]
29.
de Mulder P, Oosterhof G, Bouffioux C, et al: EORTC (30885) randomised phase III study with recombinant interferon alpha and recombinant interferon alfpha and gamma in patients with advanced renal cell carcinoma. Br J Cancer 71: 371-375, 1995[Medline]
30.
Stadler WM, Kuzel T, Dumas M, et al: A multi-center phase II trial of interleukin-2, interferon-alpha, and 13 cis-retinoic acid in patients with metastatic renal cell carcinoma. J Clin Oncol 16: 1820-1825, 1998[Abstract]
31.
Elson PJ, Witte RS, Trump DL: Prognostic factors for survival in patients with recurrent or metastatic renal cell carcinoma. Cancer Res 48: 7310-7313, 1988[Abstract/Free Full Text]
32.
De Forges A, Rey A, Klink M, et al: Prognostic factors of adult metastatic renal cell carcinoma: A multivariate analysis. Semin Surg Oncol 4: 149-154, 1988
33.
Palmer PA, Vinke J, Philip T, et al: Prognostic factors for survival in patients with advanced renal cell carcinoma treated with recombinant interleukin-2. Ann Oncol 3: 475-480, 1992[Abstract/Free Full Text]
34.
Jones M, Selby P, Franks C, et al: The impact of interleukin-2 on survival in renal cancer: A multivariate analysis. Cancer Biother 8: 275-288, 1993[Medline]
35.
Fossa SD, Kramer A, Droz JP: Prognostic factors and survival in patients with metastatic renal cell carcinoma treated with chemotherapy or interferon-alpha. Eur J Cancer 30A: 1310-1314, 1994[CrossRef]
36.
Hanninen EJ, Kirchner H, Atzpodien J: Interleukin-2–based home therapy of metastatic renal cell carcinoma: Risks and benefits in 215 consecutive patients. J Urol 155: 19-25, 1996[CrossRef][Medline]
Submitted April 26, 2001;
accepted July 31, 2001.
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|
|
D. Cella, J. C. Cappelleri, A. Bushmakin, C. Charbonneau, J. Z. Li, S. T. Kim, I. Chen, M. D. Michaelson, and R. J. Motzer
Quality of Life Predicts Progression-Free Survival in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib Versus Interferon Alfa
J. Oncol. Pract,
March 1, 2009;
5(2):
66 - 70.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Golshayan, S. George, D. Y. Heng, P. Elson, L. S. Wood, T. M. Mekhail, J. A. Garcia, H. Aydin, M. Zhou, R. M. Bukowski, et al.
Metastatic Sarcomatoid Renal Cell Carcinoma Treated With Vascular Endothelial Growth Factor-Targeted Therapy
J. Clin. Oncol.,
January 10, 2009;
27(2):
235 - 241.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Brugarolas
In Reply
J. Clin. Oncol.,
December 1, 2008;
26(34):
5653 - 5654.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. I. Rini, S. Halabi, J. E. Rosenberg, W. M. Stadler, D. A. Vaena, S.-S. Ou, L. Archer, J. N. Atkins, J. Picus, P. Czaykowski, et al.
Bevacizumab Plus Interferon Alfa Compared With Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: CALGB 90206
J. Clin. Oncol.,
November 20, 2008;
26(33):
5422 - 5428.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Schmidinger, C. C. Zielinski, U. M. Vogl, A. Bojic, M. Bojic, C. Schukro, M. Ruhsam, M. Hejna, and H. Schmidinger
Cardiac Toxicity of Sunitinib and Sorafenib in Patients With Metastatic Renal Cell Carcinoma
J. Clin. Oncol.,
November 10, 2008;
26(32):
5204 - 5212.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. H. Finke, B. Rini, J. Ireland, P. Rayman, A. Richmond, A. Golshayan, L. Wood, P. Elson, J. Garcia, R. Dreicer, et al.
Sunitinib Reverses Type-1 Immune Suppression and Decreases T-Regulatory Cells in Renal Cell Carcinoma Patients
Clin. Cancer Res.,
October 15, 2008;
14(20):
6674 - 6682.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. E. Hutson, R. A. Figlin, J. G. Kuhn, and R. J. Motzer
Targeted Therapies for Metastatic Renal Cell Carcinoma: An Overview of Toxicity and Dosing Strategies
Oncologist,
October 1, 2008;
13(10):
1084 - 1096.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. van Cruijsen, A. A.M. van der Veldt, L. Vroling, D. Oosterhoff, H. J. Broxterman, R. J. Scheper, G. Giaccone, J. B.A.G. Haanen, A. J.M. van den Eertwegh, E. Boven, et al.
Sunitinib-Induced Myeloid Lineage Redistribution in Renal Cell Cancer Patients: CD1c+ Dendritic Cell Frequency Predicts Progression-Free Survival
Clin. Cancer Res.,
September 15, 2008;
14(18):
5884 - 5892.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Garcia and D. Danielpour
Mammalian target of rapamycin inhibition as a therapeutic strategy in the management of urologic malignancies
Mol. Cancer Ther.,
June 1, 2008;
7(6):
1347 - 1354.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Bukowski
How I Treat Renal Cell Carcinoma
J. Oncol. Pract,
May 1, 2008;
4(3):
150 - 152.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A.M. van der Veldt, M. R. Meijerink, A. J.M. van den Eertwegh, A. Bex, G. de Gast, J. B.A.G. Haanen, and E. Boven
Sunitinib for Treatment of Advanced Renal Cell Cancer: Primary Tumor Response
Clin. Cancer Res.,
April 15, 2008;
14(8):
2431 - 2436.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. I. Rini
Temsirolimus, an Inhibitor of Mammalian Target of Rapamycin
Clin. Cancer Res.,
March 1, 2008;
14(5):
1286 - 1290.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. K. Rathmell, W. M. Stadler, and B. I. Rini
Rational Therapeutic Choices and Strategies for Patients with Metastatic Renal Cancer
ASCO Educational Book,
January 1, 2008;
2008(1):
192 - 198.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ebbinghaus, M. Hussain, N. Tannir, M. Gordon, A. A. Desai, R. A. Knight, R. A. Humerickhouse, J. Qian, G. B. Gordon, and R. Figlin
Phase 2 Study of ABT-510 in Patients with Previously Untreated Advanced Renal Cell Carcinoma
Clin. Cancer Res.,
November 15, 2007;
13(22):
6689 - 6695.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Mego, M. Reckova, J. Obertova, Z. Sycova-Mila, K. Brozmanova, and J. Mardiak
Increased cardiotoxicity of sorafenib in sunitinib-pretreated patients with metastatic renal cell carcinoma
Ann. Onc.,
November 1, 2007;
18(11):
1906 - 1907.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Bukowski, F. F. Kabbinavar, R. A. Figlin, K. Flaherty, S. Srinivas, U. Vaishampayan, H. A. Drabkin, J. Dutcher, S. Ryba, Q. Xia, et al.
Randomized Phase II Study of Erlotinib Combined With Bevacizumab Compared With Bevacizumab Alone in Metastatic Renal Cell Cancer
J. Clin. Oncol.,
October 10, 2007;
25(29):
4536 - 4541.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Motzer, G. R. Hudes, B. D. Curti, D. F. McDermott, B. J. Escudier, S. Negrier, B. Duclos, L. Moore, T. O'Toole, J. P. Boni, et al.
Phase I/II Trial of Temsirolimus Combined With Interferon Alfa for Advanced Renal Cell Carcinoma
J. Clin. Oncol.,
September 1, 2007;
25(25):
3958 - 3964.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Gollob, W. K. Rathmell, T. M. Richmond, C. B. Marino, E. K. Miller, G. Grigson, C. Watkins, L. Gu, B. L. Peterson, and J. J. Wright
Phase II Trial of Sorafenib Plus Interferon Alfa-2b As First- or Second-Line Therapy in Patients With Metastatic Renal Cell Cancer
J. Clin. Oncol.,
August 1, 2007;
25(22):
3288 - 3295.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. W. Ryan, B. H. Goldman, P. N. Lara Jr, P. C. Mack, T. M. Beer, C. M. Tangen, D. Lemmon, C.-X. Pan, H. A. Drabkin, and E. D. Crawford
Sorafenib With Interferon Alfa-2b As First-Line Treatment of Advanced Renal Carcinoma: A Phase II Study of the Southwest Oncology Group
J. Clin. Oncol.,
August 1, 2007;
25(22):
3296 - 3301.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Hudes, M. Carducci, P. Tomczak, J. Dutcher, R. Figlin, A. Kapoor, E. Staroslawska, J. Sosman, D. McDermott, I. Bodrogi, et al.
Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma
N. Engl. J. Med.,
May 31, 2007;
356(22):
2271 - 2281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Rabhi-Essafi, A. Sadok, N. Khalaf, and D. M. Fathallah
A strategy for high-level expression of soluble and functional human interferon {alpha} as a GST-fusion protein in E.coli
Protein Eng. Des. Sel.,
May 1, 2007;
20(5):
201 - 209.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Garcia and B. I. Rini
Recent Progress in the Management of Advanced Renal Cell Carcinoma
CA Cancer J Clin,
March 1, 2007;
57(2):
112 - 125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Cho, S. Signoretti, M. Regan, J. W. Mier, and M. B. Atkins
The Role of Mammalian Target of Rapamycin Inhibitors in the Treatment of Advanced Renal Cancer
Clin. Cancer Res.,
January 15, 2007;
13(2):
758s - 763s.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Motzer, T. E. Hutson, P. Tomczak, M. D. Michaelson, R. M. Bukowski, O. Rixe, S. Oudard, S. Negrier, C. Szczylik, S. T. Kim, et al.
Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma
N. Engl. J. Med.,
January 11, 2007;
356(2):
115 - 124.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Lam, A. Breda, A. S. Belldegrun, and R. A. Figlin
Evolving Principles of Surgical Management and Prognostic Factors for Outcome in Renal Cell Carcinoma
J. Clin. Oncol.,
December 10, 2006;
24(35):
5565 - 5575.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Parton, M. Gore, and T. Eisen
Role of Cytokine Therapy in 2006 and Beyond for Metastatic Renal Cell Cancer
J. Clin. Oncol.,
December 10, 2006;
24(35):
5584 - 5592.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Motzer and R. M. Bukowski
Targeted Therapy for Metastatic Renal Cell Carcinoma
J. Clin. Oncol.,
December 10, 2006;
24(35):
5601 - 5608.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Matsubara, Y. Mizutani, F. Hongo, H. Nakanishi, Y. Kimura, S. Ushijima, A. Kawauchi, T. Tamura, T. Sakata, and T. Miki
Gene therapy with TRAIL against renal cell carcinoma.
Mol. Cancer Ther.,
September 1, 2006;
5(9):
2165 - 2171.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. E. Eggener, O. Yossepowitch, J. A. Pettus, M. E. Snyder, R. J. Motzer, and P. Russo
Renal Cell Carcinoma Recurrence After Nephrectomy for Localized Disease: Predicting Survival From Time of Recurrence
J. Clin. Oncol.,
July 1, 2006;
24(19):
3101 - 3106.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Fernandez-Rodriguez, G. L. de Argumedo, J. M. Mane, A. Munoz, J. Ferreiro, N. Fuente, and G. Lopez-Vivanco
High-Dose Interleukin-2 in Metastatic Renal Cell Carcinoma
J. Clin. Oncol.,
September 20, 2005;
23(27):
6797 - 6798.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Atkins, M. Regan, D. McDermott, J. Mier, E. Stanbridge, A. Youmans, P. Febbo, M. Upton, M. Lechpammer, and S. Signoretti
Carbonic Anhydrase IX Expression Predicts Outcome of Interleukin 2 Therapy for Renal Cancer
Clin. Cancer Res.,
May 15, 2005;
11(10):
3714 - 3721.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Katz-Brull, N. M. Rofsky, M. M. Morrin, I. Pedrosa, D. J. George, M. D. Michaelson, R. P. Marquis, M. Maril, C. Noguera, and R. E. Lenkinski
Decreases in free cholesterol and fatty acid unsaturation in renal cell carcinoma demonstrated by breath-hold magnetic resonance spectroscopy
Am J Physiol Renal Physiol,
April 1, 2005;
288(4):
F637 - F641.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. I. Rini
VEGF-Targeted Therapy in Metastatic Renal Cell Carcinoma
Oncologist,
March 1, 2005;
10(3):
191 - 197.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. I. Rini and E. J. Small
Biology and Clinical Development of Vascular Endothelial Growth Factor-Targeted Therapy in Renal Cell Carcinoma
J. Clin. Oncol.,
February 10, 2005;
23(5):
1028 - 1043.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. M. Mekhail, R. M. Abou-Jawde, G. BouMerhi, S. Malhi, L. Wood, P. Elson, and R. Bukowski
Validation and Extension of the Memorial Sloan-Kettering Prognostic Factors Model for Survival in Patients With Previously Untreated Metastatic Renal Cell Carcinoma
J. Clin. Oncol.,
February 1, 2005;
23(4):
832 - 841.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. F. McDermott, M. M. Regan, J. I. Clark, L. E. Flaherty, G. R. Weiss, T. F. Logan, J. M. Kirkwood, M. S. Gordon, J. A. Sosman, M. S. Ernstoff, et al.
Randomized Phase III Trial of High-Dose Interleukin-2 Versus Subcutaneous Interleukin-2 and Interferon in Patients With Metastatic Renal Cell Carcinoma
J. Clin. Oncol.,
January 1, 2005;
23(1):
133 - 141.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Motzer, J. Bacik, and M. Mazumdar
Prognostic Factors for Survival of Patients with Stage IV Renal Cell Carcinoma: Memorial Sloan-Kettering Cancer Center Experience
Clin. Cancer Res.,
September 15, 2004;
10(18):
6302S - 6303S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Bukowski, S. Negrier, and P. Elson
Prognostic Factors in Patients with Advanced Renal Cell Carcinoma: Development of an International Kidney Cancer Working Group
Clin. Cancer Res.,
September 15, 2004;
10(18):
6310S - 6314S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. B. Atkins, M. Regan, and D. McDermott
Update on the Role of Interleukin 2 and Other Cytokines in the Treatment of Patients with Stage IV Renal Carcinoma
Clin. Cancer Res.,
September 15, 2004;
10(18):
6342S - 6346S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Dutcher
Mammalian Target of Rapamycin Inhibition
Clin. Cancer Res.,
September 15, 2004;
10(18):
6382S - 6387S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-J. Patard, H. L. Kim, J. S. Lam, F. J. Dorey, A. J. Pantuck, A. Zisman, V. Ficarra, K.-R. Han, L. Cindolo, A. De La Taille, et al.
Use of the University of California Los Angeles Integrated Staging System to Predict Survival in Renal Cell Carcinoma: An International Multicenter Study
J. Clin. Oncol.,
August 15, 2004;
22(16):
3316 - 3322.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. I. Rini, S. Halabi, J. Taylor, E. J. Small, and R. L. Schilsky
Cancer and Leukemia Group B 90206: A Randomized Phase III Trial of Interferon-{alpha} or Interferon-{alpha} Plus Anti-Vascular Endothelial Growth Factor Antibody (Bevacizumab) in Metastatic Renal Cell Carcinoma
Clin. Cancer Res.,
April 15, 2004;
10(8):
2584 - 2586.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. B. Atkins, M. Hidalgo, W. M. Stadler, T. F. Logan, J. P. Dutcher, G. R. Hudes, Y. Park, S.-H. Liou, B. Marshall, J. P. Boni, et al.
Randomized Phase II Study of Multiple Dose Levels of CCI-779, a Novel Mammalian Target of Rapamycin Kinase Inhibitor, in Patients With Advanced Refractory Renal Cell Carcinoma
J. Clin. Oncol.,
March 1, 2004;
22(5):
909 - 918.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Sparano, R. Gray, B. Giantonio, P. O'Dwyer, and R. L. Comis
Evaluating Antiangiogenesis Agents in the Clinic: The Eastern Cooperative Oncology Group Portfolio of Clinical Trials
Clin. Cancer Res.,
February 15, 2004;
10(4):
1206 - 1211.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Motzer, J. Bacik, L. H. Schwartz, V. Reuter, P. Russo, S. Marion, and M. Mazumdar
Prognostic Factors for Survival in Previously Treated Patients With Metastatic Renal Cell Carcinoma
J. Clin. Oncol.,
February 1, 2004;
22(3):
454 - 463.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Sosman
Targeting of the VHL-Hypoxia-Inducible Factor-Hypoxia-Induced Gene Pathway for Renal Cell Carcinoma Therapy
J. Am. Soc. Nephrol.,
November 1, 2003;
14(11):
2695 - 2702.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Hernberg, P. Virkkunen, P. Bono, H. Ahtinen, H. Maenpaa, and H. Joensuu
Interferon Alfa-2b Three Times Daily and Thalidomide in the Treatment of Metastatic Renal Cell Carcinoma
J. Clin. Oncol.,
October 15, 2003;
21(20):
3770 - 3776.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Motzer
Renal Cell Carcinoma: A Priority Malignancy for Development and Study of Novel Therapies
J. Clin. Oncol.,
April 1, 2003;
21(7):
1193 - 1194.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Nakanishi, Y. Mizutani, A. Kawauchi, O. Ukimura, T. Shiraishi, M. Hatano, M. Mizuno, J. Yoshida, and T. Miki
Significant Antitumoral Activity of Cationic Multilamellar Liposomes Containing Human IFN-{beta} Gene against Human Renal Cell Carcinoma
Clin. Cancer Res.,
March 1, 2003;
9(3):
1129 - 1135.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
TOP
ABSTRACT
INTRODUCTION
