Original Study
Clinical Outcomes and Survival of Advanced Renal Cancer Patients in Phase I Clinical Trials Laeeq Malik,1 Helen Parsons,2 Devalingam Mahalingam,1 Benjamin Ehler,2 Martin Goros,2 Alex Mejia,1 Andrew Brenner,1 John Sarantopoulos1 Abstract Clinical investigators and advanced renal cancer patients are keen in knowing the expected outcome if they enroll in clinical trials after disease progression. We conducted a retrospective study of 70 renal cancer patients who were treated in 25 phase I trials. Participation in an early phase clinical trial is a reasonable and safe option for selected patients who have exhausted standard treatment. Background/Introduction: The purpose of this study was to describe the basic demographic characteristics, and analyze the response and survival experience of advanced renal cancer subjects treated in a phase I trial. Patients and Methods: We conducted a retrospective observational study in 70 renal cancer patients participating in 25 phase I trials. Descriptive statistics, Kaplan-Meier, and multivariate Cox proportional hazards analyses were used to examine factors associated with time from study entry to treatment failure (TTF) and survival. Results: The median age at diagnosis was 56.50 years. Eastern Cooperative Oncology Group (ECOG) performance status was 0 for 23.19% (n ¼ 16) of the patients; 49.18% (n ¼ 30) had received 2 or more previous lines of systemic therapy; and 84.29% (n ¼ 59) of patients had 2 or more metastatic sites. A median number of 4.00 cycles of treatment was delivered. Four partial responses (6.25%) and 38 cases of stable disease lasting > 4 months (43.75%) were observed. The median TTF was 16.00 weeks. In multivariate analyses, men and patients with lactate dehydrogenase > 1.5 times the upper limit of normal had a shorter TTF. The median overall survival was 45.57 weeks (319.00 days). In multivariate analysis, factors predicting shorter survival were ECOG performance status 1 (P ¼ .023), age younger than 60 years (P ¼ .015), albumin < 3.4 g/dL (P ¼ .042), and liver metastases (P ¼ .010). Conclusion: Advanced renal cancer patients with select clinical characteristics could consider phase I trials after exhausting standard therapeutic options. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2014 Elsevier Inc. All rights reserved. Keywords: Metastatic, Phase I, Renal, Survival, Trial
Introduction Renal cell carcinoma (RCC) accounts for 80% to 85% of all renal malignancies.1 In the United States, there are 65,000 new cases of renal cell cancer each year.2 According to the Surveillance, Epidemiology and End Results data from 2006 to 2010, the median age for RCC at diagnosis was 64 years.3 The 5-year survival rate of patients with renal cancer is currently estimated to be 71%, attributed to recent improvements in therapeutic options.4 Radical nephrectomy with curative intent is the preferred treatment approach for patients with localized disease. Until recently, systemic 1
Institute for Drug Development, Cancer Therapy and Research Center (CTRC) Department of Epidemiology and Biostatistics University of Texas Health Science Center, San Antonio, TX 2
Submitted: Dec 6, 2013; Revised: Jan 22, 2014; Accepted: Jan 23, 2014 Address for correspondence: Laeeq Malik, MD, FRACP, Institute for Drug Development, CTRC at the University of Texas Health Science Center, San Antonio, TX 78229 E-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2014.01.011
treatment options for metastatic RCC were limited to cytokine therapy or referral for clinical trials of novel agents. With the advent of targeted therapies in the past decade, transition from cytotoxic treatments to highly selective molecules has radically altered and expanded options for cancer patients. Currently, targeted therapy using tyrosine kinase inhibitors (TKIs) and antiangiogenic agents is the preferred initial treatment approach for most patients with advanced clear-cell RCC. There are 5 such agents approved by the Food and Drug Administration (FDA) as a treatment in the firstand second-line settings.5-9 In addition, the inhibitors of mammalian target of rapamycin pathways have important clinical activity and FDA approval for use in untreated and previously treated patients with advanced RCC.10,11 Treatment planning for patients with progressive disease (PD) is challenging because there are little data regarding optimal therapy in patients in whom the previously mentioned treatments have failed. Clinical trials are recommended for such patients with good performance status in the National Comprehensive Cancer Network
Clinical Genitourinary Cancer Month 2014
-1
Renal Cancer Patients in Phase I Trials guidelines.12 The outcomes for patients with advanced stage renal cancer treated in early phase clinical trials have not been previously reported. In this retrospective review, we report on the general characteristics, time to treatment failure (TTF), prognostic factors, and survival data of advanced renal cancer patients who were enrolled in phase I trials at our tertiary cancer center.
Patients and Methods Patients and Data Acquisition The Cancer Therapy and Research Center (CTRC) is a tertiary care cancer center in San Antonio, TX. It has a well established Institute for Drug Development with a particular focus on phase I clinical trials since the early 1990s. The University of Texas Health Science Center at San Antonio has an informatics data exchange and acquisition program, which serves as a primary research data system. All renal cancer patients participating in phase I clinical trials at the CTRC from January 2002 to December 2012 were identified using this system. All patients completed an informed consent process before enrollment into a trial and all trials were approved by the CTRC Institutional Review Board. All patients with advanced renal cell cancer of any histological subtype, who were successfully enrolled in a phase I study, were included. Patients with previous treatment in a phase I clinical trial and screen failures were excluded from this analysis. Patient’s electronic medical records from the initial clinic visit to the time of last visit were reviewed. We extracted demographic data (sex, age, residence); medical information (disease site, tumor histology, date of diagnosis of metastatic disease, number and nature of previous treatments, performance status); details of first phase I trial (nature of investigational agent, date of consent, date and reason for removal from study); information on clinical outcome, subsequent treatment; and laboratory data (lactate dehydrogenase [LDH], albumin, and hemoglobin) from physicians’ clinical notes that were dictated at the time of clinic visit. All the data were entered into a password-protected database.
Outcomes Time to treatment failure was measured in weeks from study enrollment to the date the patient was removed from the study for any reason. Patients who were still continuing treatment at the time of last follow-up were censored on that date. Survival was measured in days from the date of study consent until death from any cause. Patients who were still alive at the time of last follow-up were censored on that date.
Statistical Analysis
2
-
Descriptive statistics were used to describe patient demographic and treatment characteristics according to outcome (partial response [PR], stable disease [SD], PD), including the Kruskal-Wallis test for continuous outcomes and Fisher exact test for categorical outcomes. Survival and TTF were plotted using the Kaplan-Meier method. We then used multivariable Cox proportional hazards models to examine the relationship between patient demographic, treatment characteristics, and (1) TTF and (2) hazard of death. Each multivariable model was adjusted for age (< 60 vs. 60 years), sex (male vs. female), Eastern Cooperative Oncology Group (ECOG) status (0 vs. 1), tumor histology (clear-cell vs. noneclear-cell), site of metastatic disease (liver vs. non-liver), LDH (< 1.5 vs. 1.5 upper
Clinical Genitourinary Cancer Month 2014
limit of normal [ULN]), albumin level greater than the lower limit of normal (LLN) versus less than the LLN, hemoglobin level (< 10 vs. 10), and time since initial diagnosis (< 18 months, 18-36 months, and > 36 months). These variables were all measured at the time of informed consent. For patients participating in more than 1 trial, only clinical and laboratory details from the first phase I study were obtained. Only patients with complete demographic and clinical information were included in the final multivariable models (n ¼ 57). A P value < .05 was considered statistically significant in all analyses. All analyses were performed using R 3.0.1 (The R Foundation for Statistical Computing, Vienna, Austria).
Results Preenrollment Characteristics The median age of subjects was 56.50 years (range, 44-76 years) at the time of study enrollment; more men than women were enrolled (65.71% vs. 34.29%). A large number of study participants were Hispanic American and lived out of town. ECOG performance status was 0 for 23.19% of the patients, 56.52% had ECOG performance status of 1, and 20.29% had ECOG performance status of 2. The most common histological subtypes were clear-cell (68.12%), mixed (11.59%), papillary (10.14%), and sarcomatoid (7.25%). A large percentage (84.29%) of patients had 2 metastatic sites; 31.43% had lung only, 8.57% had lymph node only, and 17.14% had liver only. Previous nephrectomy rate was 94.03%. Nearly half of the subjects had received 2 previous anticancer therapies for the metastatic disease (49.18%), including a combination of interleukin-2, TKI, bevacizumab, and chemotherapy. Other baseline characteristics are summarized in Table 1.
Treatment and Trials In total, 70 patients included in this analysis were treated in 25 phase I trials; however, only 64 were evaluable for a treatment response. Forty-six patients were treated with a single targeted agent, 18 patients with a 2-drug targeted therapy combination, and 3 patients with chemotherapy. Among the 25 phase I trials, 17 investigated single agents and 8 evaluated different combinations. Fifteen trials investigated an antibody or small molecule targeting vascular endothelial growth factor (VEGF) receptor, multiple receptor tyrosine kinases, platelet-derived growth factor receptor, fibroblast growth factor receptor, Fms-like tyrosine kinase 3, or human pp60c-Src. Five trials involved agents targeting epidermal growth factors; 3 investigated agents targeting histone deacetylation and aurora kinases separately; 2 used chemotherapy agents (gemcitabine and topotecan); and 2 involved agents with miscellaneous targets (integrin alpha-2 and insulin-like growth factor-1 receptor).
Response Best radiological response was assessed using serial computed tomography or magnetic resonance imaging scan using Response Evaluation Criteria In Solid Tumors version 1.0 or 1.1.13,14 Imaging was performed approximately every 2 or 3 cycles depending on the individual study protocol. In patients with measurable disease, the response was classified as complete, partial, stable, or PD. Of the 64 evaluable patients for tumor response, 4 confirmed PRs (6.25%) were observed, whereas 28 patients had SD > 4 months (43.75%). Another 10 patients (15.63%) achieved SD
Laeeq Malik et al Table 1 Baseline Characteristics Best Treatment Outcome b PR (n [ 4)
SD (n [ 38)
PD (n [ 22)
Total (n [ 70)
4
38
22
70
67.5 [63.8, 71.8]
58 [53.2, 65]
54.5 [52.2, 58.8]
56.5 [53, 63]
Female
1 (25)
11 (28.95)
11 (50)
24 (34.29)
Male
3 (75)
27 (71.05)
11 (50)
46 (65.71)
Local
2 (50)
22 (57.89)
12 (54.55)
40 (57.14)
Out of town
2 (50)
16 (42.11)
10 (45.45)
30 (42.86)
White
4 (100)
26 (68.42)
10 (45.45)
41 (58.57)
Hispanic
0 (0)
12 (31.58)
11 (50)
28 (40)
Other
0 (0)
Variable Age n Median [Q1, Q3]
.01
Sex
.22
Town of Residence
1
Ethnicity
.11
0 (0)
1 (4.55)
1 (1.43)
ECOG Performance Status
.02
0
1 (25)
13 (34.21)
1 (4.55)
16 (23.19)
1
3 (75)
25 (65.79)
21 (95.45)
53 (76.81)
1
1 (25)
9 (23.68)
1 (4.55)
11 (15.71)
2
3 (75)
29 (76.32)
21 (95.45)
59 (84.29)
Yes
4 (100)
35 (94.59)
19 (95)
63 (94.03)
No
0 (0)
2 (5.41)
1 (5)
4 (5.97)
Metastatic Sites, n
.11
Nephrectomy
1
Tumor Histology
.13
Clear-cell
4 (100)
27 (72.97)
12 (54.55)
47 (68.12)
Noneclear-cell/mixed
0 (0)
10 (27.03)
10 (45.45)
22 (31.88)
1
2 (50)
20 (58.82)
6 (35.29)
31 (50.82)
2
2 (50)
14 (41.18)
11 (64.71)
30 (49.18)
1 (25)
5 (13.16)
3 (14.29)
9 (13.04) 14 (20.29)
Previous Treatments, n
.26
Type of Previous Treatment TKI
Pa
.89
IL-2
1 (25)
8 (21.05)
2 (9.52)
Bevacizumab
0 (0)
1 (2.63)
2 (9.52)
3 (4.35)
Chemotherapy
0 (0)
4 (10.53)
4 (19.05)
8 (11.59)
Clinical trial
1 (25)
4 (10.53)
1 (4.76)
6 (8.7)
Multiple
1 (25)
11 (28.95)
6 (28.57)
21 (30.43)
Other
0 (0)
5 (13.16)
3 (14.29)
8 (11.59)
Single biological agent
3 (75)
27 (72.97)
12 (60)
46 (68.66)
Combination therapy
1 (25)
9 (24.32)
6 (30)
18 (26.87)
Chemotherapy
0 (0)
1 (2.7)
2 (10)
3 (4.48)
Type of Phase I Trial
.68
Reason for Withdrawal From Study
.23
Progression
3 (75)
31 (81.58)
21 (95.45)
Toxicity
0 (0)
2 (5.26)
1 (4.55)
55 (78.57) 7 (10)
Patient preference/other
1 (25)
5 (13.16)
0 (0)
8 (11.43)
Yes
1 (25)
10 (27.03)
0 (0)
11 (16.18)
No
3 (75)
27 (72.97)
21 (100)
57 (83.82)
Dose Reduction
.01
Clinical Genitourinary Cancer Month 2014
-3
Renal Cancer Patients in Phase I Trials Table 1 Continued Best Treatment Outcome b PR (n [ 4)
SD (n [ 38)
PD (n [ 22)
Total (n [ 70)
Non-liver
4 (100)
36 (94.74)
12 (54.55)
58 (82.86)
Liver
0 (0)
2 (5.26)
10 (45.45)
12 (17.14)
Variable
Pa
Clinical Outcomes and Survival of Advanced Renal Cancer Patients in Phase I Clinical Trials Laeeq Malik,1 Helen Parsons,2 Devalingam Mahalingam,1 Benjamin Ehler,2 Martin Goros,2 Alex Mejia,1 Andrew Brenner,1 John Sarantopoulos1 Abstract Clinical investigators and advanced renal cancer patients are keen in knowing the expected outcome if they enroll in clinical trials after disease progression. We conducted a retrospective study of 70 renal cancer patients who were treated in 25 phase I trials. Participation in an early phase clinical trial is a reasonable and safe option for selected patients who have exhausted standard treatment. Background/Introduction: The purpose of this study was to describe the basic demographic characteristics, and analyze the response and survival experience of advanced renal cancer subjects treated in a phase I trial. Patients and Methods: We conducted a retrospective observational study in 70 renal cancer patients participating in 25 phase I trials. Descriptive statistics, Kaplan-Meier, and multivariate Cox proportional hazards analyses were used to examine factors associated with time from study entry to treatment failure (TTF) and survival. Results: The median age at diagnosis was 56.50 years. Eastern Cooperative Oncology Group (ECOG) performance status was 0 for 23.19% (n ¼ 16) of the patients; 49.18% (n ¼ 30) had received 2 or more previous lines of systemic therapy; and 84.29% (n ¼ 59) of patients had 2 or more metastatic sites. A median number of 4.00 cycles of treatment was delivered. Four partial responses (6.25%) and 38 cases of stable disease lasting > 4 months (43.75%) were observed. The median TTF was 16.00 weeks. In multivariate analyses, men and patients with lactate dehydrogenase > 1.5 times the upper limit of normal had a shorter TTF. The median overall survival was 45.57 weeks (319.00 days). In multivariate analysis, factors predicting shorter survival were ECOG performance status 1 (P ¼ .023), age younger than 60 years (P ¼ .015), albumin < 3.4 g/dL (P ¼ .042), and liver metastases (P ¼ .010). Conclusion: Advanced renal cancer patients with select clinical characteristics could consider phase I trials after exhausting standard therapeutic options. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2014 Elsevier Inc. All rights reserved. Keywords: Metastatic, Phase I, Renal, Survival, Trial
Introduction Renal cell carcinoma (RCC) accounts for 80% to 85% of all renal malignancies.1 In the United States, there are 65,000 new cases of renal cell cancer each year.2 According to the Surveillance, Epidemiology and End Results data from 2006 to 2010, the median age for RCC at diagnosis was 64 years.3 The 5-year survival rate of patients with renal cancer is currently estimated to be 71%, attributed to recent improvements in therapeutic options.4 Radical nephrectomy with curative intent is the preferred treatment approach for patients with localized disease. Until recently, systemic 1
Institute for Drug Development, Cancer Therapy and Research Center (CTRC) Department of Epidemiology and Biostatistics University of Texas Health Science Center, San Antonio, TX 2
Submitted: Dec 6, 2013; Revised: Jan 22, 2014; Accepted: Jan 23, 2014 Address for correspondence: Laeeq Malik, MD, FRACP, Institute for Drug Development, CTRC at the University of Texas Health Science Center, San Antonio, TX 78229 E-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2014.01.011
treatment options for metastatic RCC were limited to cytokine therapy or referral for clinical trials of novel agents. With the advent of targeted therapies in the past decade, transition from cytotoxic treatments to highly selective molecules has radically altered and expanded options for cancer patients. Currently, targeted therapy using tyrosine kinase inhibitors (TKIs) and antiangiogenic agents is the preferred initial treatment approach for most patients with advanced clear-cell RCC. There are 5 such agents approved by the Food and Drug Administration (FDA) as a treatment in the firstand second-line settings.5-9 In addition, the inhibitors of mammalian target of rapamycin pathways have important clinical activity and FDA approval for use in untreated and previously treated patients with advanced RCC.10,11 Treatment planning for patients with progressive disease (PD) is challenging because there are little data regarding optimal therapy in patients in whom the previously mentioned treatments have failed. Clinical trials are recommended for such patients with good performance status in the National Comprehensive Cancer Network
Clinical Genitourinary Cancer Month 2014
-1
Renal Cancer Patients in Phase I Trials guidelines.12 The outcomes for patients with advanced stage renal cancer treated in early phase clinical trials have not been previously reported. In this retrospective review, we report on the general characteristics, time to treatment failure (TTF), prognostic factors, and survival data of advanced renal cancer patients who were enrolled in phase I trials at our tertiary cancer center.
Patients and Methods Patients and Data Acquisition The Cancer Therapy and Research Center (CTRC) is a tertiary care cancer center in San Antonio, TX. It has a well established Institute for Drug Development with a particular focus on phase I clinical trials since the early 1990s. The University of Texas Health Science Center at San Antonio has an informatics data exchange and acquisition program, which serves as a primary research data system. All renal cancer patients participating in phase I clinical trials at the CTRC from January 2002 to December 2012 were identified using this system. All patients completed an informed consent process before enrollment into a trial and all trials were approved by the CTRC Institutional Review Board. All patients with advanced renal cell cancer of any histological subtype, who were successfully enrolled in a phase I study, were included. Patients with previous treatment in a phase I clinical trial and screen failures were excluded from this analysis. Patient’s electronic medical records from the initial clinic visit to the time of last visit were reviewed. We extracted demographic data (sex, age, residence); medical information (disease site, tumor histology, date of diagnosis of metastatic disease, number and nature of previous treatments, performance status); details of first phase I trial (nature of investigational agent, date of consent, date and reason for removal from study); information on clinical outcome, subsequent treatment; and laboratory data (lactate dehydrogenase [LDH], albumin, and hemoglobin) from physicians’ clinical notes that were dictated at the time of clinic visit. All the data were entered into a password-protected database.
Outcomes Time to treatment failure was measured in weeks from study enrollment to the date the patient was removed from the study for any reason. Patients who were still continuing treatment at the time of last follow-up were censored on that date. Survival was measured in days from the date of study consent until death from any cause. Patients who were still alive at the time of last follow-up were censored on that date.
Statistical Analysis
2
-
Descriptive statistics were used to describe patient demographic and treatment characteristics according to outcome (partial response [PR], stable disease [SD], PD), including the Kruskal-Wallis test for continuous outcomes and Fisher exact test for categorical outcomes. Survival and TTF were plotted using the Kaplan-Meier method. We then used multivariable Cox proportional hazards models to examine the relationship between patient demographic, treatment characteristics, and (1) TTF and (2) hazard of death. Each multivariable model was adjusted for age (< 60 vs. 60 years), sex (male vs. female), Eastern Cooperative Oncology Group (ECOG) status (0 vs. 1), tumor histology (clear-cell vs. noneclear-cell), site of metastatic disease (liver vs. non-liver), LDH (< 1.5 vs. 1.5 upper
Clinical Genitourinary Cancer Month 2014
limit of normal [ULN]), albumin level greater than the lower limit of normal (LLN) versus less than the LLN, hemoglobin level (< 10 vs. 10), and time since initial diagnosis (< 18 months, 18-36 months, and > 36 months). These variables were all measured at the time of informed consent. For patients participating in more than 1 trial, only clinical and laboratory details from the first phase I study were obtained. Only patients with complete demographic and clinical information were included in the final multivariable models (n ¼ 57). A P value < .05 was considered statistically significant in all analyses. All analyses were performed using R 3.0.1 (The R Foundation for Statistical Computing, Vienna, Austria).
Results Preenrollment Characteristics The median age of subjects was 56.50 years (range, 44-76 years) at the time of study enrollment; more men than women were enrolled (65.71% vs. 34.29%). A large number of study participants were Hispanic American and lived out of town. ECOG performance status was 0 for 23.19% of the patients, 56.52% had ECOG performance status of 1, and 20.29% had ECOG performance status of 2. The most common histological subtypes were clear-cell (68.12%), mixed (11.59%), papillary (10.14%), and sarcomatoid (7.25%). A large percentage (84.29%) of patients had 2 metastatic sites; 31.43% had lung only, 8.57% had lymph node only, and 17.14% had liver only. Previous nephrectomy rate was 94.03%. Nearly half of the subjects had received 2 previous anticancer therapies for the metastatic disease (49.18%), including a combination of interleukin-2, TKI, bevacizumab, and chemotherapy. Other baseline characteristics are summarized in Table 1.
Treatment and Trials In total, 70 patients included in this analysis were treated in 25 phase I trials; however, only 64 were evaluable for a treatment response. Forty-six patients were treated with a single targeted agent, 18 patients with a 2-drug targeted therapy combination, and 3 patients with chemotherapy. Among the 25 phase I trials, 17 investigated single agents and 8 evaluated different combinations. Fifteen trials investigated an antibody or small molecule targeting vascular endothelial growth factor (VEGF) receptor, multiple receptor tyrosine kinases, platelet-derived growth factor receptor, fibroblast growth factor receptor, Fms-like tyrosine kinase 3, or human pp60c-Src. Five trials involved agents targeting epidermal growth factors; 3 investigated agents targeting histone deacetylation and aurora kinases separately; 2 used chemotherapy agents (gemcitabine and topotecan); and 2 involved agents with miscellaneous targets (integrin alpha-2 and insulin-like growth factor-1 receptor).
Response Best radiological response was assessed using serial computed tomography or magnetic resonance imaging scan using Response Evaluation Criteria In Solid Tumors version 1.0 or 1.1.13,14 Imaging was performed approximately every 2 or 3 cycles depending on the individual study protocol. In patients with measurable disease, the response was classified as complete, partial, stable, or PD. Of the 64 evaluable patients for tumor response, 4 confirmed PRs (6.25%) were observed, whereas 28 patients had SD > 4 months (43.75%). Another 10 patients (15.63%) achieved SD
Laeeq Malik et al Table 1 Baseline Characteristics Best Treatment Outcome b PR (n [ 4)
SD (n [ 38)
PD (n [ 22)
Total (n [ 70)
4
38
22
70
67.5 [63.8, 71.8]
58 [53.2, 65]
54.5 [52.2, 58.8]
56.5 [53, 63]
Female
1 (25)
11 (28.95)
11 (50)
24 (34.29)
Male
3 (75)
27 (71.05)
11 (50)
46 (65.71)
Local
2 (50)
22 (57.89)
12 (54.55)
40 (57.14)
Out of town
2 (50)
16 (42.11)
10 (45.45)
30 (42.86)
White
4 (100)
26 (68.42)
10 (45.45)
41 (58.57)
Hispanic
0 (0)
12 (31.58)
11 (50)
28 (40)
Other
0 (0)
Variable Age n Median [Q1, Q3]
.01
Sex
.22
Town of Residence
1
Ethnicity
.11
0 (0)
1 (4.55)
1 (1.43)
ECOG Performance Status
.02
0
1 (25)
13 (34.21)
1 (4.55)
16 (23.19)
1
3 (75)
25 (65.79)
21 (95.45)
53 (76.81)
1
1 (25)
9 (23.68)
1 (4.55)
11 (15.71)
2
3 (75)
29 (76.32)
21 (95.45)
59 (84.29)
Yes
4 (100)
35 (94.59)
19 (95)
63 (94.03)
No
0 (0)
2 (5.41)
1 (5)
4 (5.97)
Metastatic Sites, n
.11
Nephrectomy
1
Tumor Histology
.13
Clear-cell
4 (100)
27 (72.97)
12 (54.55)
47 (68.12)
Noneclear-cell/mixed
0 (0)
10 (27.03)
10 (45.45)
22 (31.88)
1
2 (50)
20 (58.82)
6 (35.29)
31 (50.82)
2
2 (50)
14 (41.18)
11 (64.71)
30 (49.18)
1 (25)
5 (13.16)
3 (14.29)
9 (13.04) 14 (20.29)
Previous Treatments, n
.26
Type of Previous Treatment TKI
Pa
.89
IL-2
1 (25)
8 (21.05)
2 (9.52)
Bevacizumab
0 (0)
1 (2.63)
2 (9.52)
3 (4.35)
Chemotherapy
0 (0)
4 (10.53)
4 (19.05)
8 (11.59)
Clinical trial
1 (25)
4 (10.53)
1 (4.76)
6 (8.7)
Multiple
1 (25)
11 (28.95)
6 (28.57)
21 (30.43)
Other
0 (0)
5 (13.16)
3 (14.29)
8 (11.59)
Single biological agent
3 (75)
27 (72.97)
12 (60)
46 (68.66)
Combination therapy
1 (25)
9 (24.32)
6 (30)
18 (26.87)
Chemotherapy
0 (0)
1 (2.7)
2 (10)
3 (4.48)
Type of Phase I Trial
.68
Reason for Withdrawal From Study
.23
Progression
3 (75)
31 (81.58)
21 (95.45)
Toxicity
0 (0)
2 (5.26)
1 (4.55)
55 (78.57) 7 (10)
Patient preference/other
1 (25)
5 (13.16)
0 (0)
8 (11.43)
Yes
1 (25)
10 (27.03)
0 (0)
11 (16.18)
No
3 (75)
27 (72.97)
21 (100)
57 (83.82)
Dose Reduction
.01
Clinical Genitourinary Cancer Month 2014
-3
Renal Cancer Patients in Phase I Trials Table 1 Continued Best Treatment Outcome b PR (n [ 4)
SD (n [ 38)
PD (n [ 22)
Total (n [ 70)
Non-liver
4 (100)
36 (94.74)
12 (54.55)
58 (82.86)
Liver
0 (0)
2 (5.26)
10 (45.45)
12 (17.14)
Variable
Pa
