Kenneth H. Kim

At What Cost Does a Potential Survival Advantage of Bevacizumab Make Sense for the Primary Treatment of Ovarian Cancer? A Cost-Effectiveness Analysis

PURPOSE To determine whether the addition of bevacizumab to paclitaxel and carboplatin for the primary treatment of advanced ovarian cancer can be cost effective. METHODS A cost-effectiveness analysis compared the three arms of the Gynecologic Oncology Group (GOG) 218 study (paclitaxel plus carboplatin [PC], PC plus bevacizumab [PCB], and PCB plus bevacizumab maintenance [PCB+B]). Actual and estimated costs of treatment plus the potential costs of complications were established for each strategy. Progression-free survival (PFS) and bowel perforation rates were taken from recently reported results of GOG 218. Sensitivity analysis was performed for pertinent uncertainties in the model. Incremental cost-effectiveness ratios (ICERs) per progression-free life-year saved (PF-LYS) were estimated. RESULTS For the 600 patients entered onto each arm of GOG 218 at the baseline estimates of PFS and bowel perforation, the cost of PC was

A cohort study evaluating robotic versus laparotomy surgical outcomes of obese women with endometrial carcinoma

2.5 million, compared with

A phase I clinical trial of Ad5/3-Δ24, a novel serotype-chimeric, infectivity-enhanced, conditionally-replicative adenovirus (CRAd), in patients with recurrent ovarian cancer

21.4 million for PCB and

A Phase I Clinical Trial of Ad5.SSTR/TK.RGD, a Novel Infectivity-Enhanced Bicistronic Adenovirus, in Patients with Recurrent Gynecologic Cancer

78.3 million for PCB+B. These costs led to an ICER of

Simvastatin, an HMG-CoA reductase inhibitor, exhibits anti-metastatic and anti-tumorigenic effects in endometrial cancer

479,712 per PF-LYS for PCB and

Building a successful fertility preservation program at a major cancer center.

401,088 per PF-LYS for PCB+B. When the cost of bevacizumab was reduced to 25% of baseline, the ICER of PCB+B fell below

Outpatient end of life discussions shorten hospital admissions in gynecologic oncology patients

100,000 per PF-LYS. ICERs were not substantially reduced when the perforation rate was equal across all arms. CONCLUSION The addition of bevacizumab to standard chemotherapy in patients with advanced ovarian cancer is not cost effective. Treatment with maintenance bevacizumab leads to improved PFS but is associated with both direct and indirect costs. The cost effectiveness of bevacizumab in the adjuvant treatment of ovarian cancer is primarily dependent on drug costs.

Obesity is associated with worse quality of life in women with gynecologic malignancies: An opportunity to improve patient‐centered outcomes

OBJECTIVE Minimally invasive surgery offers advantages for management of obese patients, but technical difficulty often deters its utilization. Compared to laparotomy, robotic surgery should allow comparable staging and improved surgical outcomes. Therefore, we evaluated outcomes in robotic and laparotomy cohorts of obese women with endometrial cancer at our institution. METHODS Retrospective robotic and laparotomy cohorts of obese women (BMI ≥ 30 kg/m(2)) undergoing surgical management of primary endometrial cancer from March 2006 to March 2009 were formulated utilizing a computerized database. Patient demographics, operative statistics, peri-operative complications, and pathologic details were collected in an intent to treat analysis. Chi-square or Fishers exact test and t-test were used for statistical analysis. RESULTS 73 women underwent robotic surgical management, 11% converted to laparotomy. Mean BMI (39.8 vs. 41.9, p=0.152), number of co-morbidities (2.49 vs. 2.62, p=0.690), number of previous surgeries (0.97 vs. 0.94, p=0.841), and lymphadenectomies performed (65.8% vs. 56.7%, p=0.227) were similar between cohorts. Total lymph nodes obtained were not statistically different between cohorts (8.01 vs. 7.24, p=0.505). Total operative time and room time was significantly longer for robotic surgery; however, estimated blood loss, the percentage of patients receiving transfusion, hospital length of stay, wound complications (4.1% vs. 20.2%, p=0.002) and other complications (9.6% vs. 29.8%, p=0.001) were improved for the robotic cohort. CONCLUSIONS Robotic management of obese women with endometrial cancer yields acceptable staging results and improved surgical outcomes. Although operating time is longer, hospital time is shorter. Robotic surgery may be an ideal approach for these patients.

A New Generation of Serotype Chimeric Infectivity-Enhanced Conditionally Replicative Adenovirals: The Safety Profile of Ad5/3-Δ24 in Advance of a Phase I Clinical Trial in Ovarian Cancer Patients

OBJECTIVE The conditionally replicative adenovirus Ad5/3-Δ24 has a type-3 knob incorporated into the type-5 fiber that facilitates enhanced ovarian cancer infectivity. Preclinical studies have shown that Ad5/3-Δ24 achieves significant oncolysis and anti-tumor activity in ovarian cancer models. The purpose of this study was to evaluate in a phase I trial the feasibility and safety of intraperitoneal (IP) Ad5/3-Δ24 in recurrent ovarian cancer patients. METHODS Eligible patients were treated with IP Ad5/3-Δ24 for 3 consecutive days in one of three dose cohorts ranging 1 × 10(10)-1 × 10(12)vp. Toxicity was assessed utilizing CTC grading and efficacy with RECIST. Ascites, serum, and other samples were obtained to evaluate gene transfer, generation of wildtype virus, viral shedding, and antibody response. RESULTS Nine of 10 patients completed treatment per protocol. A total of 15 vector-related adverse events were experienced in 5 patients. These events included fever or chills, nausea, fatigue, and myalgia. All were grades 1-2 in nature, transient, and medically managed. Of the 8 treated patients evaluable for response, six patients had stable disease and 2 patients had progressive disease. Three patients had decreased CA-125 from pretreatment levels one month after treatment. Ancillary biologic studies indicated Ad5/3-Δ24 replication in patients in the higher dose cohorts. All patients experienced an anti-adenoviral neutralizing antibody effect. CONCLUSIONS This study suggests the feasibility and safety of a serotype chimeric infectivity-enhanced CRAd, Ad5/3-Δ24, as a potential therapeutic option for recurrent ovarian cancer patients.

Incidence of mechanical malfunction in low-profile subcutaneous implantable venous access devices in patients receiving chemotherapy for gynecologic malignancies

Purpose: Ad5.SSTR/TK.RGD is an infectivity-enhanced adenovirus expressing a therapeutic thymidine kinase suicide gene and a somatostatin receptor (SSTR) that allows for noninvasive gene transfer imaging. The purpose of this study was to identify the maximum tolerated dose (MTD), toxicities, clinical efficacy, and biologic effects of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer. Experimental Design: Eligible patients were treated intraperitoneally for 3 days with 1 × 109 to 1 × 1012 vp/dose of Ad5.SSTR/TK.RGD followed by intravenous ganciclovir for 14 days. Toxicity and clinical efficacy were assessed using Common Toxicity Criteria (CTC) Adverse Events grading and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Imaging using In-111 pentetreotide was obtained before and after treatment. Tissue samples were obtained to evaluate for gene transfer, generation of wild-type virus, viral shedding, and antibody response. Results: Twelve patients were treated in three cohorts. The most common vector-related clinical toxicities were grade I/II constitutional or pain symptoms, experienced most often in patients treated at the highest dose. MTD was not identified. Five patients showed stable disease; all others experienced progressive disease. One patient with stable disease experienced complete resolution of disease and normalization of CA125 on further follow-up. Imaging detected increased In-111 pentetreotide retention in patients treated at the highest dose. Ancillary studies showed presence of Ad5.SSTR/TK.RGD virus and HSV1-tk expression in ascites samples collected at various time points in most patients treated within the higher dose cohorts. Conclusions: This study shows the safety, potential efficacy, and possible gene transfer imaging capacity of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer. Further development of this novel gene therapeutic appears to be warranted. Clin Cancer Res; 18(12); 3440–51. ©2012 AACR.