[show abstract][hide abstract] ABSTRACT: The landscape of treatment for metastatic renal cell carcinoma (mRCC) continues to evolve. Although several new drugs have been approved for the treatment of this disease in recent years, mRCC remains incurable. Thus, the search continues for new effective therapies. One such novel compound is axitinib (Inlyta, Pfizer), a potent vascular endothelial growth factor receptor tyrosine kinase inhibitor. Following phase I testing in advanced solid tumors (where hypertension, stomatitis, and diarrhea were the dose-limiting toxicities), use of axitinib has been further developed through phase II testing in thyroid, breast, lung, and renal cancers. Recently, the phase III AXIS (Axitinib [AG 013736] as Second Line Therapy for Metastatic Renal Cell Cancer) trial demonstrated an improvement in progression-free survival for patients with mRCC who were treated with axitinib versus sorafenib (Nexavar, Bayer) as second-line therapy. This article describes the preclinical and clinical evolution of axitinib, with an emphasis on its development and role in mRCC.
Clinical advances in hematology & oncology: H&O 05/2012; 10(5):307-14.
[show abstract][hide abstract] ABSTRACT: As more centers develop robotic proficiency, progressing to a successful robot-assisted partial nephrectomy (RAPN) program depends on a number of factors. We describe our technique, results, and analysis of program setup for RAPN.
Between 2005 and 2011, 92 RAPNs were performed following maturation of a robotic prostatectomy program. Operating rooms and supply rooms were outfitted for efficient robotic throughput. Tilepro and intraoperative ultrasound were used for all cases. Training and experiential learning for surgeons, anesthesia and nursing staff was a high priority. An onsite robotic technician helped troubleshoot, prepare the room and staff prior to starting surgery, and provide assistance with different robotic models.
Average operative time decreased over time from 235 min to 199 min (p = .03). Warm ischemia time decreased from 26 minutes to 23 minutes (p = .02) despite an increased complexity of tumors and operations on multiple tumors. Median estimated blood loss was 150 mL. Average length of hospital stay was 3 days (range 1-9). Average size of lesions was 2.7 cm (range 0.7-8.6). Final pathology demonstrated 71 (77%) malignant lesions and 21 (23%) benign lesions.
The addition of a robot-assisted partial nephrectomy program to an institutional robotic program can be coordinated with several key steps. Outcomes from an operational, oncologic, and renal functional standpoint are acceptable. Despite increased complexity of tumors and treatment of multiple lesions, operative and warm ischemia times showed a decrease over time. An organizational model that involves the surgeons, anesthesia, nursing staff, and possibly a robotic technical specialist helps to overcome the learning curve.
The Canadian Journal of Urology 04/2012; 19(2):6193-200. · 0.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the functional outcomes and complications for patients with bladder cancer undergoing robotic-assisted laparoscopic radical cystectomy with Indiana pouch continent cutaneous urinary diversion.
From February 2004 to March 2010, 34 patients underwent robotic-assisted laparoscopic radical cystectomy with Indiana pouch continent cutaneous urinary diversion reconstruction. After surgery, the complications were identified, categorized, and graded using an established 5-grade modification of the original Clavien grading system, and continence was assessed. Descriptive statistics were used in evaluating the outcomes. Fischer's exact test was used in the comparison of early and late Clavien grade III complications.
Overall, 175 (123 early and 52 late) complications after surgery were reported in 32 (94%) of 34 patients. Within 90 days of surgery, 31 (91%) of 34 patients experienced ≥ 1 early complication. Of 34 patients, 15 (44%) reported ≥ 1 late complications (>90 days). Most (85% and 69%, respectively) early and late complications were graded as minor (grade II or less). Fewer patients with early complications required an additional intervention (grade III) compared with patients with late complications (14% vs 31%; P = .116). The most common complication in both intervals was infection, reported in 22% and 37% of patients with early and late complications, respectively. The continence data for 31 patients at a mean follow-up of 20.1 months (median 12.0) showed that all but 1 patient (97%) had daytime and nighttime continence.
Patients undergoing robotic-assisted laparoscopic radical cystectomy with Indiana pouch continent cutaneous urinary diversion reconstruction have comparable complication rates and functional outcomes compared with patients in the open series.
[show abstract][hide abstract] ABSTRACT: With six agents approved for metastatic renal cell carcinoma (mRCC) within the past 5 years, there has undoubtedly been progress in treating this disease. However, the goal of cure remains elusive, and the agents nearest approval (i.e., axitinib and tivozanib) abide by the same paradigm as existing drugs (i.e., inhibition of VEGF or mTOR signaling). The current review will focus on investigational agents that diverge from this paradigm. Specifically, novel immunotherapeutic strategies will be discussed, including vaccine therapy, cytotoxic T-lymphocyte antigen 4 (CTLA4) blockade, and programmed death-1 (PD-1) inhibition, as well as novel approaches to angiogenesis inhibition, such as abrogation of Ang/Tie-2 signaling. Pharmacologic strategies to block other potentially relevant signaling pathways, such as fibroblast growth factor receptor or MET inhibition, are also in various stages of development. Although VEGF and mTOR inhibition have dramatically improved outcomes for patients with mRCCs, a surge above the current plateau with these agents will likely require exploring new avenues.
Molecular Cancer Therapeutics 03/2012; 11(3):526-37. · 5.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: The objective of our study was to determine whether dorsal venous complex (DVC) control technique influences positive apical margins following robotic assisted laparoscopic radical prostatectomy (RALRP).
One thousand fifty-eight patients who underwent RALRP at City of Hope from June 2007 to October 2009 were assessed. Endoscopic stapling and suture ligature of the DVC were compared. Positive apical margins were identified and compared based on DVC-control technique. Recurrence probability was estimated using the Kaplan-Meier method, and logistic regression analysis was used to predict the odds of positive apical margins.
Of 1058 patients, 633 (60%) underwent endoscopic stapling, and 425 (40%) had suture ligature. The groups had similar baseline characteristics including age and body mass index. We observed a statistically different PSA (5.4 ng/mL versus 5.2 ng/mL, p = 0.03) and operative time (2.8 hours versus 2.7 hours, p = 0.02) between stapling and suture groups, but the actual difference was small. Operative time, Gleason score, pathologic stage, and overall positive margin rates were not significantly different between groups. Positive apical margins were observed in 39 (6%) and 27 (6%) patients in the staple and suture groups, respectively. Multivariate analysis showed that the positive apical margin rate was greater in patients with higher pathologic stage and final pathological Gleason score.
During RALRP, there is no difference in positive apical margin rate when the DVC is controlled using either endoscopic stapling or suture ligature. However, patients with a higher pathologic stage and final pathologic Gleason score are at higher risk for positive apical surgical margins.
The Canadian Journal of Urology 02/2012; 19(1):6147-54. · 0.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: The advanced age and comorbidities often associated with bladder cancer patients creates a difficult scenario regarding further management. Robotic-assisted laparoscopic radical cystectomy (RALRC) has had favorable results as a minimally invasive treatment option. We studied perioperative outcomes of RALRC in octogenarians to discern if there is any added benefit in this patient population.
One hundred and sixty robotic cystectomies have been performed between October 2003 and June 2010. We identified 24 octogenarians who underwent RALRC and form the cohort of the study.
Mean patient age was 84.7 years and mean BMI was 24 kg/m². Most of the patients in the study had serious medical comorbidities, as 82.6% of them had an ASA classification ≥ 3 and 95.6% had Charlson scores ≥ 3. There was one open conversion and two patients had positive surgical margins. There were a total of 45 complications in the study, with 14 major complications observed in the 90-day period after surgery. There were five patients who had no complications, and two patients expired as a result of multiple organ failure. At 24 months the overall, disease-free and disease-specific survivals were 51.1%, 64.3%, and 79%, respectively. The 90-day mortality rate was 8.7%.
Octogenarians undergoing RALRC have a significant risk of morbidity and mortality. The relationship between advanced age and oncologic outcomes or complications needs to be discerned further as it relates to the octogenarian. Further study is needed to delineate the safety and efficacy of this approach.
International Journal of Medical Robotics and Computer Assisted Surgery 01/2012; 8(2):247-52. · 1.49 Impact Factor
[show abstract][hide abstract] ABSTRACT: Both locally advanced and metastatic renal cell carcinoma (RCC) present a challenge in terms of their optimal management. This article reviews the literature and evaluates the role of surgery in the treatment of advanced RCC. Surgery is the optimal treatment for locally advanced RCC and minimal, resectable, metastatic disease. Patients with metastatic disease, and some forms of locally advanced disease, may also benefit from multimodal management with local surgical therapy and systemic treatment using either immunotherapy or targeted therapy. Regardless of the disease stage, patients with locally advanced or metastatic RCC represent heterogenous patient populations with different disease characteristics and risk factors. Individualization of care in the setting of a sound oncologic framework may optimize the risk/benefit ratio within individual patient cohorts.
Journal of the National Comprehensive Cancer Network: JNCCN 09/2011; 9(9):985-93. · 5.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Within the past two years, three agents have garnered approval from the US FDA for the specific treatment of metastatic castration resistant prostate cancer (mCRPC) - (1) abiraterone, (2) cabazitaxel and (3) sipuleucel-T. In separate phase III studies, each agent led to an improvement in overall survival (OS) of 2-4 months over a suitable comparator. With these costly therapies all having potential application in the patient with mCRPC, multiple entities (industry, government, and the general public) must strategize to determine how the cost burden of these agents can be balanced with the potential gains for the individual patient. Herein, we provide a framework with which to approach this dilemma.
[show abstract][hide abstract] ABSTRACT: INTRODUCTION: Prostate cancer is the second leading cause of cancer death in men in the USA, and most of these deaths will occur as a result of castrate-resistant prostate cancer (CRPC) that has progressed despite androgen deprivation therapy. There has been better understanding of castration resistance and molecular mechanisms of prostate cancer progression recently, leading to new treatment strategies. AREAS COVERED: This review focuses on emerging and new therapies for castrate-resistant prostate cancer, including hormonal therapy, immunotherapy and cytotoxic agents. EXPERT OPINION: New treatment strategies have been developed in recent years and, with improved understanding of advanced CRPC, additional targeted treatments are expected in the near future. Further cost effectiveness research of these treatments is warranted before dissemination of these promising agents.
Expert Opinion on Pharmacotherapy 06/2011; 12(13):2069-74. · 2.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: Robotic technology has enabled urologists to perform a variety of laparoscopic surgeries. Robotic surgery offers enhanced optical magnification and visualization with precise surgical movements. We report the first case series of robot-assisted laparoscopic retroperitoneal lymph node dissection for clinical stage I nonseminomatous testicular cancer in three consecutive patients. All procedures were performed using a modified template nerve-sparing approach. The mean patient age was 31 yr. Estimated blood loss was 150-200 ml; operative time was 150-240 min. Length of stay was 2 d, and there were no perioperative complications. This early series in carefully selected and well-informed patients represented a limited experience. These results may not be applicable to all surgeons. Further long-term follow-up with a larger number of patients are warranted to validate these preliminary findings.
European Urology 03/2011; 60(6):1299-302. · 10.48 Impact Factor