Clinical Genitourinary Cancer - Articles in Press

The Role of IMiDs Alone or in Combination in Prostate Cancer - Corrected Proof

Chadi Nabhan, Daniel P. Petrylak — 2012-05-21

Abstract: Recent insights into mechanisms by which prostate cancer becomes castration resistant have allowed better and more rational therapeutic design. These novel therapies have complemented the modest success that chemotherapy has shown in recent years changing the landscape of this disease and leading to improved outcomes. Angiogenesis and immune deregulation are 2 pathways that have increasingly been shown to lead into castration resistant prostate cancer (CRPC). Thalidmide and lenalidomide are immunomodulatory agents with antiangiogenesis properties that have shown activity in this setting with acceptable safety profile. In this review, we discuss briefly the different mechanisms that render prostate cancer castration resistant and elaborate on thalidomide and lenalidomide data in CRPC after reviewing their theoretic mechanisms of action. This timely review coincides with the identification of newer therapies against CRPC affirming our steady movement toward better disease control.

Neutrophil Number after Interferon-Alfa Treatment is an Independent Predictive Marker of Overall Survival in Metastatic Renal Cell Carcinoma - Corrected Proof

Takeshi Azuma, Yukihide Matayoshi, Yasushi Nagase, Masaya Oshi — 2012-05-21

Micro-Abstract: Immunotherapy using interferon-alpha (INF-α) is indicated for patients with metastatic renal cancer. In this study, we retrospectively evaluated the previously reported predictive markers and some immunologic factors in 84 patients with metastatic renal cell carcinoma (RCC) who underwent INF-α treatment. We found that the number of neutrophils after IFN-α treatment could be an independent predictive marker. This finding is useful for deciding whether INF-α therapy should be continued. Abstract: Background: The purpose of this study was to assess the outcome in patients treated by immunotherapy using interferon-alpha (IFN-α) and to evaluate the significance of the neutrophil count after IFN-α immunotherapy as a predictive marker for metastatic renal cell carcinoma (RCC). Patients and Methods: We identified 84 patients with metastatic RCC who underwent immunotherapy with IFN-α between 1998 and 2006. The predictive values of the neutrophil count before and after IFN-α treatment as well as other clinical and laboratory parameters were assessed retrospectively. Results: On univariate analysis, the significant correlation with overall survival (OS) was recognized in the Eastern Cooperative Oncology Group (ECOG) performance score (PS), lactate dehydrogenase (LDH) levels, corrected calcium levels, interval from diagnosis to treatment, and the ratio of neutrophil number before and after treatment with INF-α. Multivariate analysis showed that ECOG PS, corrected calcium levels, interval from diagnosis to treatment and neutrophil number after IFN-α treatment were independent factors for OS. Using the number of neutrophils after IFN-α treatment, subgroups were identified using the Memorial Sloan-Kettering Cancer Center (MSKCC) model. The 1-year survival rate was 93% vs. 63% in the intermediate-risk group and 34% vs. 8% in the poor-risk group. In the favorable-risk group, all patients had a good decrease in neutrophil number after treatment with IFN-α. Conclusion: Neutrophil number after IFN-α treatment can be a good predictive marker for OS in metastatic RCC. By combining MSKCC score with neutrophil number after treatment with IFN-α, we can subdivide each group.

Prolonged Therapy With Cabazitaxel in an Octogenarian With Metastatic Castration-Resistant Prostate Cancer - Corrected Proof

Sumanta K. Pal, Cy A. Stein — 2012-05-11

A Phase II Trial of Intrapatient Dose-Escalated Sorafenib in Patients With Metastatic Renal Cell Carcinoma - Corrected Proof

Robert Amato, Jim Zhai, James Willis, Somyata Saxena, Melissa DeFoe — 2012-05-03

Micro-Abstract: Sorafenib has been demonstrated in second-line setting with limited significant adverse events at a dose of 400 mg twice a day (b.i.d.) in patients with metastatic renal cell carcinoma; yet, the question remains if higher doses will have greater clinical activity with manageable adverse events. Forty-six patients who failed cytokine treatment received dose escalation sorafenib that started at 400 mg b.i.d. and ending with 800 mg b.i.d.; they were evaluated for response rate, progression-free survival, and overall survival. The high-dose sorafenib was tolerated by the patients, and 8 patients achieved complete response, 13 patients achieved partial response, and 21 patients had stable disease. Abstract: Purpose: Sorafenib has been demonstrated as second-line therapy, with limited significant adverse events at a dose of 400 mg twice a day (b.i.d.) in patients with metastatic renal cell carcinoma. This study evaluated the ability of patients to dose-escalate, response rate, progression-free survival (PFS), and overall survival. Methods: The initial dose of sorafenib was 400 mg b.i.d.. Dose escalation of sorafenib to 600 mg b.i.d. occurred from days 29-56 and increased to 800 mg b.i.d. on day 57 and beyond as tolerated. Dose modifications were performed for toxicity per the National Cancer Institute Common Toxicity Criteria version 3.0. The patients were evaluated every 2 cycles (8 weeks) by using Response Evaluation Criteria in Solid Tumors version 1.0. Results: Forty-four patients were evaluable for response. Median age was 62.5 years, 39 patients had a Karnofsky Perfomance Status of 100%. Twenty-two patients received no prior therapy. Of the evaluable patients, 42 were dose escalated to 600 mg b.i.d., and 74% (31) of these were further dose escalated to 800 mg b.i.d.. Eight patients had a complete response (CR), 13 patients demonstrated a partial response (PR), and 21 patients had stable disease. Common treatment-related adverse events included hypertension, hand-foot syndrome, skin rash, diarrhea, dry skin, alopecia, and facial redness. Discussion: The majority of patients were escalated to 600 mg b.i.d. or 800 mg b.i.d.. Intrapatient dose-escalated sorafenib has promising antitumor activity as demonstrated by a 48% CR-PR rate (21 patients). Antitumor activity is further suggested by a prolonged PFS ≥6 months in 64% (28) of patients. Significant antitumor activity and reversible adverse events has been demonstrated in escalated doses of sorafenib.

Metastatic Extraosseous Ewing's Sarcoma (EES)/Primitive Neuroectodermal Tumor (PNET) of the Kidney: 8-Year Durable Response After Induction and Maintenance Chemotherapy - Corrected Proof

2012-04-16

A Randomized Trial Comparing Tamoxifen Therapy vs. Tamoxifen Prophylaxis in Bicalutamide-Induced Gynecomastia - Corrected Proof

2012-04-13

Micro-Abstract: The activity of tamoxifen (TAM) in counteracting bicalutamide-induced breast events has been tested in 117 patients with carcinoma of the prostate. Bicalutamide-induced breast events (BEs) can be significantly prevented by prophylaxis with TAM 10 mg/day or effectively treated with TAM therapy 20 mg/day. The difference in prevalence of gynecomastia and breast pain between the 2 arms of this series both favored tamoxifen prophylaxis. Abstract: Background: Tamoxifen (TAM) has been shown to be active against the bicalutamide-induced breast events (BEs) gynecomastia, and breast pain in patients with prostate cancer (PC). Optimal doses and schedules are not yet established. Debate still exists about whether prophylaxis with TAM is more effective than treatment of BEs when diagnosed. The results of a randomized study comparing TAM prophylaxis vs. TAM therapy are presented. Methods: One hundred seventy-six patients with prostate cancer (PC) who were candidates for bicalutamide monotherapy were randomized to receive TAM 20 mg daily orally within 1 month from the onset of BEs (arm A) vs. TAM 10 mg daily starting simultaneously with bicalutamide (arm B). TAM was administered for up to 1 year. BEs were evaluated by a self-administered visual analogue scale. Neither ultrasonography nor calipers were used to measure the degree of gynecomastia. Results: In arm A, BEs showed a prevalence, increasing with time up to 78.3%. After therapy with TAM they persisted in 27.7% of cases. Two patients (3%) interrupted TAM therapy because of dizziness, and 3 patients (4%) interrupted bicalutamide therapy because of painful gynecomastia. In arm B, the prevalence of BEs was 35% after 12 months of therapy. The difference in BEs between the 2 arms was statistically significant (P < .0001). The differences in prevalence of gynecomastia and breast pain between the 2 arms both favored TAM prophylaxis (P < .0001 and P < .001, respectively). Up to 35% of patients had BEs of low intensity, never requiring bicalutamide withdrawal. Two patients (3%) interrupted the treatment because of gastrointestinal intolerance. No difference emerged between the 2 arms in terms of prostate-specific antigen (PSA) response, plasma testosterone levels, and tumor progression. Conclusion: Bicalutamide-induced BEs can be prevented to a significant degree by prophylaxis with TAM 10 mg/day or effectively treated with TAM therapy 20 mg/day. Persisting BEs are of higher intensity after therapy than after prophylaxis.

Malignant Fibrous Histiocytoma of the Spermatic Cord in a Patient With Polycystic Kidney Disease; Review of the Literature - Corrected Proof

2012-04-09

Cabazitaxel Rechallenge at Prostate-Specific Antigen Relapse After Previous Cabazitaxel and Docetaxel Chemotherapy: Case Report - Corrected Proof

Christina J. Perry, Santhanam Sundar — 2012-03-26

Enduring Response to Everolimus as Third-Line Therapy in a Patient With Advanced Renal Cell Carcinoma, Including Small-Bowel Metastases: Loss of FHIT but Normal VHL Gene Status - Corrected Proof

2012-03-22

Prostate Cancer Stem Cells - Corrected Proof

Shi-Ming Tu, Sue-Hwa Lin — 2012-03-16

Abstract: Stem cells have long been implicated in prostate gland formation. The prostate undergoes regression after androgen deprivation and regeneration after testosterone replacement. Regenerative studies suggest that these cells are found in the proximal ducts and basal layer of the prostate. Many characteristics of prostate cancer indicate that it originates from stem cells. For example, the putative androgen receptor–negative (AR–) status of prostate stem cells renders them inherently insensitive to androgen blockade therapy. The androgen-regulated gene fusion TMPRSS2-ERG could be used to clarify both the cells of origin and the evolution of prostate cancer cells. In this review, we show that the hypothesis that distinct subtypes of cancer result from abnormalities within specific cell types—the stem cell theory of cancer—may instigate a major paradigm shift in cancer research and therapy. Ultimately, the stem cell theory of cancers will affect how we practice clinical oncology: our diagnosis, monitoring, and therapy of prostate and other cancers.

Response of Metastatic Renal Medullary Carcinoma to Carboplatinum and Paclitaxel Chemotherapy - Corrected Proof

2012-03-14

Spontaneous Regression of Thoracic Metastases While Progression of Brain Metastases After Stereotactic Radiosurgery and Stereotactic Body Radiotherapy for Metastatic Renal Cell Carcinoma: Abscopal Effect Prevented by the Blood-Brain Barrier? - Corrected Proof

2012-03-14

A Primary Signet Ring Cell Carcinoma of the Prostate With Bone Metastasis With Impressive Response to FOLFOX and Cetuximab - Corrected Proof

2012-03-14

Development of Novel Immune Interventions for Prostate Cancer - Corrected Proof

Neeraj Agarwal, Sumanth Padmanabh, Nicholas J. Vogelzang — 2012-03-14

Abstract: Prostate cancer is the leading cause of cancer-related morbidity and mortality in men in the Western world. Use of traditional and newer therapeutic regimens is constrained in terms of tolerance, efficacy, and cross-resistance. There is a need for newer therapies without overlapping mechanisms of action and toxicities to improve the outcome. Advances in the field of immunology and cancer biology have led to an improved understanding of the interactions between the immune system and tumors, propelling the field of cancer vaccines to the forefront of clinical investigation. Recent US Food and Drug Administration approval of sipuleucel-T, an autologous dendritic cell–based vaccine for the treatment of castration refractory prostate cancer, represents a significant advancement in the field of cancer vaccines. However, the overall survival benefits with sipuleucel-T are modest at best, and the field of cancer vaccine therapy is in a continuous state of evolution and expansion. Further improvements are expected to result from the selection of more appropriate tumor antigens, which circumvent immune tolerance, and from the development of more effective immunization strategies aimed at inducing an effective cytotoxic T-cell response. This review summarizes recent developments in the field of immunotherapy in prostate cancer with a focus on dendritic cell vaccines, virus-based vaccines, DNA-based vaccines, cell-based vaccines, peptide-based vaccine and therapies blocking immune checkpoints to break peripheral immune tolerance.

Prevalence and Predictors of Benign Lesions in Renal Masses Smaller Than 7 cm Presumed to be Renal Cell Carcinoma - Corrected Proof

2012-03-09

Micro-Abstract: The present study was designed to determine the incidence and predictive factors of benign renal lesions in 450 patients who underwent surgical removal of solitary renal masses <7 cm in diameter. Of the 450 renal masses, 88 (19.9%) were benign lesions. Female sex, nephron-sparing surgery, surgery between 1990 and 1996, cystic components on imaging, and small tumors (<4 cm) were independently associated with benign pathology. Abstract: Purpose: To determine the association between preoperative parameters with final benign pathology in patients who underwent surgical removal of solitary renal masses <7 cm in diameter. Materials and Methods: A database of 450 patients without metastatic disease who underwent radical nephrectomy or nephron-sparing surgery (NSS) for removal of renal masses <7 cm between January 1990 and December 2009 was reviewed. Age, sex, symptoms, year and type of surgery, solid or cystic appearance, and tumor size were analyzed as presumed predictors of benign pathology. Multivariate analysis was performed to identify parameters associated with benign pathology. Results: In all, 88 (19.9%) of the tumors were benign, including 39 (8.7%) oncocytomas and 22 (4.9%) angiomyolipomas. The benign lesion rate for tumors ≤2, 2.1-4, and 4.1-7 cm was 30.3%, 27.1%, and 12.5%, respectively (2P < .001). For the periods of 1990-1996, 1997-2003, and 2004-2009, the frequency of benign tumors was 25%, 17.3%, and 18.4% (2P = .271), the incidental tumor rate was 48.1%, 60.4%, and 63.8% (2P = .027), mean tumor size was 5, 4.6, and 4.1 cm (2P < .001), and the NSS rate was 28.8%, 43.2%, and 52.7% (2P < .001), respectively. Logistic regression analysis revealed that female sex, NSS, surgery between 1990 and 1996, cystic components on imaging, and small tumors (<4 cm) based on radiologic examination were independently associated with benign pathology (odds ratio [OR] = 3.26, 2.56, 2.43, 2.41, and 1.96, respectively). Conclusions: The incidence of incidental and small tumors amenable to NSS increased over time. Female sex was the strongest predictor of benign pathology.

Neuroendocrine Differentiation in Castration-Resistant Prostate Cancer: A Systematic Diagnostic Attempt - Corrected Proof

2012-03-09

Micro-Abstract: We propose a composite and reproducible neuroendocrine differentiation (NED)– assessing panel—including plasma chromogranin A (p-CgA), tissular CgA (t-CgA), somatostatin receptor 2 (SSTR2), and Ki-67—of needle biopsy specimens to be applied to patients with castration-resistant prostate cancer (CRPC). In our series, a high prevalence (85.1%) of NED was found. Neuroendocrine markers were associated with high prostate-specific antigen (PSA) levels, aggressive (high initial Gleason Score) and rapidly progressive disease, and consequent decreased overall survival (OS). Abstract: Background: Assessing the neuroendocrine (NE) pattern in castration-resistant prostate cancer (CRPC) may prove useful in selecting potential responders to target therapies such as somatostatin analogues. The aim of this study was to define a panel of markers or examinations appropriate to characterize NE differentiation (NED). Methods: Forty-seven patients with CRPC underwent a systematic diagnostic attempt to characterize the NE phenotype using a plasma blood test for chromogranin A (CgA) and immunohistochemical staining of needle biopsy–obtained specimens (CgA, somatostatin receptor 2 [SSTR2], Ki-67, and androgen receptors). In a subgroup of 26 patients, somatostatin receptor scintigraphy using 111In-DTPA-d-Phe octreotide (octreotide scintigraphy; Octreoscan, Covidien, Hazelwood, MO) was also performed. Results: NED was found in 85.1% of patients (if serum CgA, tissular CgA, and tissular SSTR2 were considered separately: 54%, 67%, and 58%, respectively). Only 15% of the 26-patient subgroup had an abnormal octreotide scintigraphy result. Although p-CgA and t-CgA were associated with more aggressive disease with a worse prognosis, patients with positive tissular SSTR2 staining had longer overall survival (OS). Conclusion: This systematic approach to explore the NED in a quite homogeneous group of patients with CRPC seems reproducible and appropriate. Further investigations are required to validate this panel and better characterize potential responders to targeted therapy.

Expression of microRNAs in the Urine of Patients With Bladder Cancer - Corrected Proof

2012-03-05

Micro-Abstract: We quantified the urine sediment and supernatant levels of microRNA (miRNA) targets related to epithelial-mesenchymal transition in 51 patients with bladder cancer and in 24 controls. We found that patients with bladder cancer had depressed levels of the miR-200 family, miR-192, and miR-155 in urinary sediment. The urinary level of these miRNAs may be developed as noninvasive markers for bladder cancer. Abstract: Background: MicroRNAs (miRNA) have been implicated to play an important role in the pathogenesis of a variety of cancers. We studied the levels of miRNAs related to epithelial-mesenchymal transition (EMT) in the urine of patients with bladder cancer. Method: The expression of the miR-200 family, miR-205, miR-192, miR-155, and miR-146a in the urine sediment and supernatant of 51 patients with bladder cancer and in 24 controls was determined by real-time quantitative polymerase chain reaction. Results: Compared with controls, the patients with bladder cancer had a lower expression of the miR-200 family, miR-192, and miR-155 in the urinary sediment; lower expression of miR-192; and higher expression of miR-155 in the urinary supernatant. The expression of the miR-200 family, miR-205, and miR-192 in the urine sediment significantly correlated with urinary expression of EMT markers, including zinc finger E-box-binding homeobox 1, vimentin, transforming growth factor β1, and Ras homolog gene family, member A. Furthermore, the levels of miR-200c and miR-141 in the urine sediment became normalized after surgery. Conclusion: We found that the urinary miR-200 family, miR-155, miR-192, and miR-205 levels are depressed in patients with bladder cancer. The level of these miRNA targets in urine has the potential to be developed as noninvasive markers for bladder cancer.

Phase II Trial of Weekly Ixabepilone in Men With Metastatic Castrate-Resistant Prostate Cancer (E3803): A Trial of the Eastern Cooperative Oncology Group - Corrected Proof

Glenn Liu, Yu-Hui Chen, Robert DiPaola, Michael Carducci, George Wilding — 2012-03-05

Micro-Abstract: Ixabepilone is an epothilone B analogue with activity in a variety of solid malignancies, including prostate cancer. The main dose-limiting toxicity of ixabepilone is myelosuppression when administered by using an every 3-week schedule. Here we evaluate the activity of a weekly ixabepilone in men with metastatic castrate-resistant prostate cancer to minimize hematologic toxicity. Abstract: Purpose: BMS-247550 (ixabepilone) is an epothilone B analogue with activity in taxane-resistant cancer cell lines. Here we report the activity and toxicity of ixabepilone, administered by using a weekly schedule, in men with metastatic castrate-resistant prostate cancer (CRPC). Experimental Design: Patients with metastatic CRPC received ixabepilone at 20 mg/m2 intravenous weekly x 3, in 4-week cycles. This noncomparative study stratified patients to either a chemotherapy naive (CN), prior taxane (Tax) only, or 2 prior cytotoxic (TCx) chemotherapy arm. The primary endpoint was prostate-specific antigen response by using PCWG (Prostate Cancer Working Group) 1 criteria. Secondary endpoints included radiographic response when using RECIST (Response Evaluation Criteria In Solid Tumors). Results: In total, 124 patients were enrolled, of whom, 109 were eligible (35 CN, 42 Tax, and 32 TCx) for the primary response determination in this study. Prostate-specific antigen responses were seen in 12 (34.3%) of 35, 12 (28.6%) of 42, and 7 (21.9%) of 32 patients with the partial objective response in 5 (22.7%) of 22, 2 (8.0%) of 25, and 0 (0.0%) of 24 patients for the CN, Tax, and TCx arms, respectively. Significant (grade 3/4) neutropenia was seen in 6 (15.4%), 7 (14.6%), and 9 (25.0%); and grade 3/4 sensory neuropathy was seen in 8 (20.5%), 12 (25.0%), and 12 (33.3%) for CN, Tax, and TCx, respectively. Grade 3/4 thrombocytopenia was infrequent and seen in only one patient on the CN and the TCx arm. Conclusion: Ixabepilone was found to have an acceptable toxicity profile when administered by using a weekly schedule with less myelosuppression compared with prior studies when using the every 3-week schedule. Single-agent activity was observed and met prespecified activity levels for the Tax treated arm.

Ras Association Domain Family 1A: A Promising Prognostic Marker in Recurrent Nonmuscle Invasive Bladder Cancer - Corrected Proof

2012-03-01

Micro-Abstract: The aim of this study was to investigate the value of RASSF1A methylation as a prognostic marker in bladder cancer. RASSF1A hypermethylation from 301 specimens of primary BC tissue was assessed using methylation-specific PCR. Among patients with recurrent NMIBC, RASSF1A methylation was identified as an independent predictor of cancer progression. Abstract: Introduction: Aberrant methylation of promoter CpG islands is an important inactivation mechanism of tumor suppressors and tumor-related genes. Ras association domain family 1A (RASSF1A) promoter hypermethylation was shown to be associated with bladder cancer (BC), but its prognostic value remains unclear. The aim of the present study was to investigate the value of RASSF1A methylation as a prognostic marker in BC. Materials and Methods: Primary BC tissues were obtained from 301 patients and included 186 specimens of nonmuscle invasive bladder cancer (NMIBC) and 115 specimens of muscle invasive bladder cancers (MIBC). RASSF1A hypermethylation was assessed using methylation-specific polymerase chain reaction (MS-PCR). The association between RASSF1A hypermethylation and clinicopathologic features, and the prognostic significance of RASSF1A hypermethylation were evaluated by Kaplan-Meier and multivariate Cox regression analyses. Results: RASSF1A promoter hypermethylation was detected in 33.6% of BCs and occurred more frequently in MIBC (46.1%) than in NMIBC (25.8%) (P < .001). In NMIBC, RASSF1A methylation was associated with advanced tumor stage (P = .026) and high grade (P < .001). Among patients with recurrent NMIBC, RASSF1A methylation was associated with shorter time to progression by Kaplan-Meier analysis (log-rank test; P = .004) and identified as an independent predictor of cancer progression by multivariate Cox regression analysis (hazard ratio [HR], 8.559; P = .014). Conclusions: Our results suggest that methylated RASSF1A may be a potential prognostic marker in patients with recurrent NMIBC.

Epidemiologic Trends in Renal Cell Carcinoma in the Cytokine and Post-Cytokine Eras: A Registry Analysis of 28,252 Patients - Corrected Proof

2012-03-01

Micro-Abstract: Advances in the targeted treatment of renal cell cancer (RCC) have shown improvements in survival in clinical trials and have largely replaced cytokine therapies as the standard of care. However it is unclear if these advances have translated to the general RCC population. We present a retrospective study of a large clinical cancer registry that demonstrates statistically significant improvements in survival in cancer patients, but the causes of this improvement are difficult to determine because of many confounders. Abstract: Background: Before 2004, advanced renal cell cancer (RCC) therapy consisted primarily of cytokines such as interferon and/or interleukin-2. Subsequently, randomized trials of targeted therapies have shown a survival benefit, leading to the approval of several new agents since 2004. Whether the survival benefit seen in highly selected patients accrued to these trials has already translated to the general RCC patient population is unclear. To explore this, a large RCC patient registry was evaluated for changes in outcome between the cytokine (1998-2003) and post-cytokine (2004-2007) eras. Methods: Data from the California Cancer Registry (CCR), a population-based cancer surveillance system, was used to retrospectively analyze 28,252 patients with RCC diagnosed between 1998 and 2007. Inter-era differences in clinical variables—including year of diagnosis, histologic characteristics, age, sex, race, stage, nephrectomy status, overall survival (OS), and cause-specific survival (CSS)—were assessed. Univariate and multivariate Cox models were used. Results: Crude 3-year OS (68.2% vs. 74.6%; 2P < .001) and CSS (78.1% vs. 82.3%; 2P < .001) were significantly higher in the post–cytokine era. In multivariate analysis, the 3 strongest predictors for improved survival were localized disease (hazard ratio [HR], 18.1; 95% confidence interval [CI], 16.6-19.6), nephrectomy (HR, 2.87; 95% CI, 2.68-3.08), and clear cell histologic type (HR, 1.33; 95% CI, 1.22-1.44). Conclusions: In this analysis of a large RCC registry, there was an apparent increase in crude OS and CSS in the post–cytokine era compared with the cytokine era. Insufficient follow-up time in the post–cytokine era and a higher proportion of localized disease in that era confound the possibility of benefit derived from targeted therapies. Longer follow-up for patients treated in the post–cytokine era is necessary for a more robust comparison of long-term OS.

Importance of Fibroblast Growth Factor Receptor in Neovascularization and Tumor Escape from Antiangiogenic Therapy - Corrected Proof

Philip J. Saylor, Bernard Escudier, M. Dror Michaelson — 2012-03-01

Abstract: Therapeutic inhibition of pathways involved in angiogenesis has become the standard of care in renal cell carcinoma (RCC). Most currently available antiangiogenic agents inhibit the vascular endothelial growth factor (VEGF) pathway. Although these drugs have produced exciting benefits, some tumors do not respond to these agents. In addition most if not all tumors that initially respond will eventually develop resistance. Tumor escape from antiangiogenic therapy may include various signaling pathways that are involved in angiogenesis, including the fibroblast growth factor (FGF) signaling pathway. Emerging preclinical data suggest that FGF and VEGF act distinctly and synergistically to promote tumor vascularization. The current review discusses the role of FGF signaling in resistance to anti-VEGF therapies and outlines potential therapeutic implications.

A Case Report of Putative Autoimmunity to Prostate Cancer After Immune-Mediated Rejection of Melanoma Through a Shared Tumor Antigen - Corrected Proof

2012-01-27

Complete Response After Sequential Sunitinib-Sorafenib Treatment In a Patient With Renal Cell Carcinoma: A Case Report - Corrected Proof

Elena Verzoni, Rodolfo Lanocita, Giuseppe Procopio — 2012-01-09