Kinjal Parikh

Maintenance Therapy Containing Metformin and/or Zyflamend for Advanced Prostate Cancer: A Case Series.

Metformin is derived from galegine, a natural ingredient, and recent studies have suggested that metformin could enhance the antitumor effects of hormone ablative therapy or chemotherapy and reduce prostate cancer-specific mortality. Zyflamend is a combination of herbal extracts that reduces inflammation and comprises turmeric, holy basil, green tea, oregano, ginger, rosemary, Chinese goldthread, hu zhang, barberry, and basil skullcap. We propose a maintenance regimen with metformin and/or Zyflamend that targets cancer stem cells and the tumor microenvironment to keep the cancer dormant and prevent it from activation from dormancy. Herein, we report the clinical course of four patients who experienced a clinical response after treatment with metformin and/or Zyflamend.

A Novel Use of Olaparib for the Treatment of Metastatic Castration‐Recurrent Prostate Cancer

Although mortality from prostate cancer has declined over the past 20 years as a result of early detection and treatment, the 5‐year survival rate for men with prostate cancer who develop metastatic disease is only 29%. Current treatment options for metastatic castration‐recurrent prostate cancer (mCRPC) are associated with toxicity and a limited durable response; therefore, additional lines of efficacious and minimally toxic therapy are needed. Olaparib, a poly(adenosine 5′‐diphosphate) ribose polymerase (PARP) inhibitor, received a U.S. Food and Drug Administration breakthrough therapy designation in January 2016 for the treatment of patients with BRCA1/2 or ATM gene‐mutated mCRPC based on results of a compelling phase II trial of olaparib in patients with advanced castration‐resistant prostate cancer (TOPARP‐A). This study found that men with mCRPC and genetic mutations in DNA damage repair genes had an overall response rate of nearly 90% with olaparib treatment. In this review, we describe current therapies for mCRPC, the rationale for anti‐PARP therapies, the pharmacology of olaparib for prostate cancer, clinical trials of olaparib for mCRPC, our clinical experience with olaparib for prostate cancer at a comprehensive cancer center, and future directions of olaparib for the treatment of mCRPC. Olaparib may constitute a promising treatment to prolong survival in patients with mCRPC, with an acceptable adverse effect profile. As the role of PARP inhibition in prostate cancer and other malignancies becomes further elucidated, olaparib may be shown to be beneficial for other patient populations.

Conditional survival of metastatic renal cell carcinoma patients treated with high-dose interleukin-2

Conditional survival (CS) is a clinically useful prediction measure which adjusts a patient’s prognosis based on their duration of survival since initiation of therapy. CS has been described in numerous malignancies, and recently described in patients with metastatic renal cell carcinoma (mRCC) who received vascular endothelial growth factor tyrosine kinase inhibitor (VEGFTKI) therapy. However, CS has been not reported in the context of mRCC treated with high-dose interleukin-2 therapy (HDIL-2). A total of 176 patients with histologically confirmed metastatic clear cell RCC (mccRCC) treated with HDIL-2 at the University of Utah Huntsman Cancer Institute from 1988–2012 were evaluated. Using the Heng/IMDC model, they were stratified by performance status and prognostic risk groups. Two-year CS was defined as the probability of surviving an additional two years from initiation of HDIL-2 to 18 months after the start of HDIL-2 at three-month intervals. The median overall survival (OS) was 19.9 months. Stratifying patients into favourable (n = 35; 20%), intermediate (n = 110; 63%), and poor (n = 31; 18%) prognostic groups resulted in median OS of 47.5 (HR 0.57, 95% CI 0.35–0.88, p = 0.0106 versus intermediate), 19.6 (HR 0.33, 95% CI 0.10–0.33, p < 0.0001 versus poor), and 8.8 (HR 5.34, 95% CI 3.00–9.62, p < 0.0001 versus favourable) months respectively. Two-year overall CS increased from 43% at therapy initiation to 100% at 18 months. These results have significant ramifications in prognostication. Furthermore, it is important when counseling patients with mccRCC who have completed treatment with HDIL-2 and are in active follow-up.

High-dose neoadjuvant intensity modulated radiotherapy/chemotherapy for distal rectal cancer followed by rectal sparing TEM.

756Background: In patients with distal rectal cancer, preoperative chemoradiotherapy remains the standard of care, however intensity modulated radiation therapy (IMRT) followed by trans-anal endoscopic microsurgery (TEM) may be able to provide more conformal and higher hoses of radiation while sparing normal tissue. It is our intent to present 11 years of experience of patients treated concurrently with chemotherapy and IMRT followed by rectal sparing TEM. We will report on local control, disease free survival (DFS), and toxicity. Methods: Forty-two patients at Lankenau Medical Center were treated for distal rectal carcinoma with IMRT and TEM from 2004 to 2016. Patients staged T1-T3 N0 M0 received 5580 cGy to the pelvis using a 9 field plan or volumetric arc therapy targeting rectal tumor and pelvic lymph nodes. The median age was 68. All patients received concurrent 5FU based chemotherapy; 54% received an infusional regimen and 46% received oral capecitabine. All patients went on to surgery with full thi...

Association between rigors and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with high-dose interleukin-2 (HD IL-2).

487 Background: HD IL-2 is associated with an objective response rate of 16-20% with durability of response in select mRCC patients. HD IL-2 is also associated with significant toxicity including vascular leak syndrome and inflammatory side effects. Few predictive markers can identify patients likely to respond to HD IL-2. Methods: Patients treated with HD IL-2 at the University of Utah Huntsman Cancer Institute from 2000 to 2012 with clear cell mRCC were evaluated. Grade of toxicities during HD IL-2 treatment were collected based on provider documentation in the electronic health record. Rates of adverse events (AEs) and overall survival stratified grade 3 AEs were evaluated by Kaplan-Meier survival estimates and Cox proportional hazards models. All AEs were graded per common terminology criteria version 4. Grade 3 rigors were defined as severe rigors requiring opioids. Results: A total of 85 patients were included with a median age of 56 years (range 32-76 years) and 79% (n = 67) were male. Patients bel...

Association of clinical parameters and overall survival (OS) in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with high-dose interleukin-2 (HD IL-2).

476 Background: HD IL-2 immunotherapy can provide durable responses in mRCC, but has a high incidence of severe adverse events (AEs). Therefore, determining pts most likely to achieve response before and during HD-IL2 treatment will help clinicians and pts best utilize HD IL-2 for the treatment of mRCC. Methods: Sequential clear cell mRCC pts treated with HD IL-2 at the University of Utah Huntsman Cancer Institute from 2000 to 2012 were included. The following clinical parameters were assessed: AE incidence, type and severity; total dose of IL-2 received and use of a 40 MIU dose cap; baseline weight, age, gender and MSKCC prognostic risk; and systemic therapy pre- or post-HD IL-2. Univariate and multivariate analyses were constructed using COX Proportional Hazard model. Results: 85 pts with clear cell mRCC treated with HD IL-2 were included with a median age of 56 years (range 32-76). Pts belonged to the following MSKCC categories: 11 (13%) good, 70 (82%) intermediate, and 4 (5%) poor risk. The median OS ...

Clinical benefit (CB) of high-dose interleukin-2 (HD IL-2) in clear cell (cc) metastatic renal cell carcinoma (mRCC).

461 Background: HD IL-2, an immunotherapy, is a standard of care for a select group of patients (pts) with mRCC. Generally objective response (OR) rates, i.e. complete response (CR) + partial response (PR), of 16-20% are discussed with pts, but not disease stabilization (SD). Recent data suggest that cancer immunotherapy may improve survival without inducing OR. Thus, treatment with HD IL-2 may provide survival benefit to an additional group of pts not experiencing OR, but only SD as the best response. Here we report CB ( OR+SD), and specifically report outcomes of cc mRCC pts experiencing SD as the best response, on treatment with HD IL-2. Methods: All sequential cc mRCC pts treated with HD IL-2 at the University of Utah Huntsman Cancer Institute from 2000-2012 were included. Pts were evaluated for best response, progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS). Two practitioners independently reviewed HD IL-2 response with discrepancies adjudicated by a third revie...