Clinical practice guidelines decrease unnecessary Pap tests in survivors of gynecologic malignancies

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ABSTRACTS / Gynecologic Oncology 120 (2011) S2–S133

bowel perforation, and progression-free survival (PFS) were analyzed to determine cost and efficacy and establish a favorable incremental cost-effectiveness ratio (ICER) per life-year saved (LYS). Results: For the 240 patients entered into each arm of the OCEANS trial, and with the baseline estimates of PFS (8.6 months for the GC group and 11 months for the GCB + B group, assuming 21% improvement of new treatment) and bowel perforation, the cost of GC was $4.0 million, compared with $36.5 million for GCB + B. These costs resulted in an ICER of $677,250 per LYS for GCB + B compared with GC. If one were to assume a PFS of 15 months (six additional months of benefit) associated with GCB + B, then this results in an ICER of $253,968. Using a maximum ICER threshold of $100,000 per LYS to deem an intervention as cost effective, the cost of B would have to be decreased by 76% or the PFS extended to 25 months for GCB + B. If no additional risk of intestinal perforation is attributed to the addition of B (2% all arms and 25% of them are fatal perforation), the ICER in GCB + B would continue to exceed $665,229 per LYS. Conclusions: In this exploratory analysis of the OCEANS trial, the addition of bevacizumab to combination chemotherapy for the treatment of recurrent ovarian cancer is associated with significant costs with potential benefits. Further investigations are warranted.

around port site (two patients), port malfunction (one patient), pain and port malfunction (two patients), port erosion into small bowel (one patient). Median PFS since the initiation of IP chemotherapy was 12 months (95% CI: 7.5–16.4) and median OS was 51 months (95% CI: 40.8–61.1). Conclusions: Intraperitoneal chemotherapy is an efficacious option for patients with recurrent epithelial ovarian carcinoma, with high completion rates, low frequency of complications and meaningful extension in survival. Further assessment in randomized controlled trials is warranted.

doi:10.1016/j.ygyno.2010.12.074

68 Clinical practice guidelines decrease unnecessary Pap tests in survivors of gynecologic malignancies L. Meyer1, K. Schmeler1, J. Wallbillich2, D. Urbauer1, P. Soliman1, M. Frumovitz1, C. Burke1, D. Bodurka1, C. Levenback1 1 University of Texas M.D. Anderson Cancer Center, Houston, TX, 2 University of Texas Medical School, Houston, TX

doi:10.1016/j.ygyno.2010.12.073

67 Intraperitoneal chemotherapy for recurrent ovarian cancer appears efficacious with high completion rates and low complications M. Skaznik-Wikiel, J. Lesnock, W. McBee, S. Taylor, S. Beriwal, A. Smith, K. Zorn, S. Richard, T. Krivak, R. Edwards Magee–Womens Hospital of the UPMC, Pittsburgh, PA Objective: Three prospective phase III clinical trials have shown a benefit of intraperitoneal (IP) chemotherapy as a front-line therapy in the treatment of ovarian cancer. However, little is known about the use of IP chemotherapy in recurrent ovarian cancer. The purpose of this descriptive study was to determine progression-free survival (PFS), overall survival (OS), completion rates, and frequency of complications in patients with epithelial ovarian cancer (EOC) treated with IP chemotherapy for recurrent disease. A retrospective, single-institution analysis of women who received IP chemotherapy for recurrent EOC between January 2005 and April 2010 was conducted. Study patients were identified from the tumor registry. PFS and OS were estimated by Kaplan–Meier methods. Results: A total of 56 women who received IP chemotherapy for their first EOC recurrence were identified. Their mean age was 56.7 years (range: 43–79). All patients had previously undergone primary surgical cytoreduction followed by intravenous platinum-based chemotherapy. Fifty-four patients (96.4%) had previously completed at least six cycles of IV chemotherapy. All patients were considered platinum sensitive. Among the patients, 80.4% were initially diagnosed with advanced-stage disease (stage IIIA–IV). All patients underwent secondary cytoreduction at the time of IP port placement; 65.3% were considered optimally cytoreduced (< 1 cm residual disease) at the end of the secondary debulking surgery. Forty-four patients (78.6%) were able to successfully complete at least six cycles of IP chemotherapy. Reasons for noncompletion were: disease progression (five patients), allergic reaction (three patients), elevated creatinine (one patient), pain (one patient), severe nausea and vomiting (one patient), death (one patient), and patient refusal (one patient). Six patients (10.7%) developed port complications: pain

Objective: Widespread use of the Pap test has had minimal impact on the early diagnosis of recurrent disease in survivors of gynecologic cancers. The use of clinical practice guidelines (CPGs) is a welldescribed approach to reduce practice variation, control cost, and improve quality of health care. The objective of this study was to demonstrate the effectiveness of performance improvement strategies to alter practice patterns with the aim of decreasing the number of unindicated Pap tests performed for surveillance in gynecologic cancer patients by 50%. A multidisciplinary operations team oversees outpatient care provided by 13 gynecologic oncologists and 20 midlevel providers who perform 13,400 patient visits annually at a single institution. The team identified Pap test utilization as a target for improvement, used a fishbone diagram to identify specific barriers (see figure), approved the new CPGs, and constructed a communication plan and project map. A convenience sample of patient visits to the practice during weeks two and four of August 2009 and August 2010 was used to represent practice patterns before and after the implementation of the CPG. For analysis, the percentage of total and unindicated (based on newly adopted CPGs) Pap tests performed out of all visits during each two-week period were calculated. Fisher's exact test was used for comparison. We estimated 80% power to detect a difference as low as 10.5%. Results: Four hundred sixty-six patient visits occurred in the 2009 study period. One hundred two of the 466 (21.88%) patients had Pap tests performed during the two-week interval in 2009. Unindicated Pap tests were performed at 41 of 466 visits (8.80%). Four hundred thirty-eight patient visits occurred in the 2010 study period. Sixty-six of 438 (15.06%) had Pap tests performed. Unindicated Pap tests were performed at 19 of 438 (4.34%) visits, indicating a 50% reduction. The introduction of the CPGs correlated with a significant decrease in the proportion of total Pap tests performed (OR = 0.63, P = 0.01), as well as in the proportion of visits on which an unindicated Pap test was performed (OR = 0.47, P = 0.01). The cost per test is estimated at $170. By decreasing Pap test utilization from 22 to 15% of visits, 938 fewer tests would be performed annually with an estimated savings of $159,535. Conclusions: The quality improvement process can successfully effect meaningful change in complex clinical settings. We now aim to eliminate all unindicated Pap tests. We are using the same tools to

ABSTRACTS / Gynecologic Oncology 120 (2011) S2–S133

reduce practice variation and costly overutilization in other aspects of our practice.

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Conclusions: Gemcitabine, carboplatin and bevacizumab constituted an effective regimen with acceptable toxicity in platinum-sensitive recurrent EOC. The response rate compared with that reported for the doublet gemcitabine and carboplatin is provocative. The degree to which schedule, dosing and the addition of bevacizumab improved response merits further study, and future testing of this regimen is warranted.

doi:10.1016/j.ygyno.2010.12.076

70 A phase I clinical trial of a novel infectivity-enhanced suicide gene adenovirus with gene transfer imaging capacity in patients with recurrent gynecologic cancer K. Kim, M. Wang, M. Barnes, J. O'Malley, Z. You, M. Preuss, G. Siegal, K. Zinn, D. Curiel, R. Alvarez University of Alabama, Birmingham, AL

doi:10.1016/j.ygyno.2010.12.075

69 A phase II study of gemcitabine, carboplatin and bevacizumab for the treatment of platinum-sensitive recurrent ovarian cancer E. Eisenhauer1, V. Zanagnolo2, D. Cohn1, R. Salani1, D. O'Malley1, G. Sutton3, B. Cobb1, M. Vaughan1, J. Fowler1, L. Copeland1 1 Ohio State University, Columbus, OH, 2European Institute of Oncology, Milan, Italy, 3St. Vincent Hospital, Indianapolis, IN

Objective: The doublet gemcitabine and carboplatin is FDA approved for the treatment of recurrent ovarian cancer, with a response rate of 47%. Multiagent chemotherapy with bevacizumab has been shown to improve survival in many disease settings. We set out to determine the activity of gemcitabine, carboplatin and bevacizumab in the setting of first recurrence of platinum-sensitive ovarian cancer. This is a phase II study of gemcitabine 1000 mg/m², carboplatin AUC 3, and bevacizumab 10 mg/kg administered intravenously on days one and 15 every 28 days for six cycles or up to 24 cycles if clinical benefit occurred. Eligible patients had platinum-sensitive recurrent EOC, primary peritoneal cancer or fallopian tube cancer without prior treatment for recurrence. Study objectives included response rate, toxicity and survival. Response rate was defined by Response Evaluation Criteria in Solid Tumors, or CA-125 criteria for patients without measurable disease. Results: Forty-five patients were accrued and received treatment. Of these, 45 were evaluable for toxicity and 39 were evaluable for response (five patients completing therapy, one patient not assessable). Of those patients evaluable for response, the overall response rate was 70%; there were 12 complete responses (30%) and 16 partial responses (40%). Seven patients had stable disease (16%), and four patients progressed (10%). Grade 3 and 4 hematologic toxic effects included neutropenia (71%), thrombocytopenia (31%), and anemia (11%); there were no episodes of febrile neutropenia. Grade 3 and 4 nonhematologic toxic effects included fatigue (16%), pain (9%), nausea (4%) and vomiting (4%). Other noted toxic effects included one small bowel abscess, one cerebrovascular accident and intracranial hemorrhage. Survival endpoints are not yet mature.

Objective: To circumvent limitations in cancer cell infectivity and invasive means of assessing gene transfer, we developed an infectivity-enhanced adenovirus, Ad5.RGD.TK/SSTr, which expresses a therapeutic thymidine kinase suicide gene and a somatostatin type 2 receptor. Preclinical studies have previously validated the therapeutic and imaging potential of this novel reagent. The purpose of this phase I study was to identify the maximum tolerated dose, the spectrum of toxicity, the potential clinical efficacy, and biologic effects of Ad5.RGD.TK/SSTr in patients with recurrent ovarian or other select gynecologic cancers. Eligible patients were treated intraperitoneally with Ad5.RGD. TK/SSTr for 3 consecutive days in one of three dose cohorts ranging from 1 × 109 to 1 × 1012 vp/dose and subsequently treated with intravenous ganciclovir for 14 days. Octreoscans were obtained on patients before and after Ad5.RGD.TK/SSTr treatment to assess for gene transfer. Toxicity was assessed using standard CTC grading. Clinical efficacy was evaluated using RECIST criteria 1 month after treatment. Ascites, serum, and other samples were obtained to evaluate for gene transfer, generation of wild-type virus, viral shedding and antibody response. Results: A total of nine patients were treated in three treatment cohorts. Clinical adverse events classified as possibly or definitely associated with the administration of Ad5.RGD.TK/SSTr included three episodes of flu-like symptoms, one episode of fever and one episode of abdominal pain. All were grade 1 and transient in nature. There were no vector-specific laboratory adverse events. The maximum feasible dose was 1 × 1012 vp/dose. Three patients had stable disease; all others progressed. On further follow-up, one of the three patients with stable disease had normalization of her CA-125 and near-complete resolution of measurable disease. Octreoscans did not demonstrate evidence of gene transfer in the first two cohorts of patients. Ancillary studies demonstrated gene transfer in ascites cellular samples in eight of nine treated patients, limited viral shedding and robust anti-adenoviral immune response. Conclusions: This study further validates the feasibility, tolerability, and potential clinical utility of infectivity-enhanced adenovirus-based gene therapeutics in gynecologic cancer. Further development of Ad5. RGD.TK/SSTr appears to be warranted.

doi:10.1016/j.ygyno.2010.12.077