Patient and physician factors associated with participation in cervical and uterine cancer trials: an NRG/GOG247 study.

PURPOSE: The aim of this study was to identify patient and physician factors related to enrollment onto Gynecologic Oncology Group (GOG) trials. METHODS: Prospective study of women with primary or recurrent cancer of the uterus or cervix treated at a GOG institution from July 2010 to January 2012. Logistic regression examined probability of availability, eligibility and enrollment in a GOG trial. Odds ratios (OR) and 95% confidence intervals (CI) for significant (p<0.05) results reported. RESULTS: Sixty institutions, 781 patients, and 150 physicians participated, 300/780 (38%) had a trial available, 290/300 had known participation status. Of these, 150 women enrolled (59.5%), 102 eligible did not enroll (35%), 38 (13%) were ineligible. Ethnicity and specialty of physician, practice type, data management availability, and patient age were significantly associated with trial availability. Patients with >4 comorbidities (OR 4.5; CI 1.7-11.8) had higher odds of trial ineligibility. Non-White patients (OR 7.9; CI 1.3-46.2) and patients of Black physicians had greater odds of enrolling (OR 56.5; CI 1.1-999.9) in a therapeutic trial. Significant patient therapeutic trial enrollment factors: belief trial may help (OR 76.9; CI 4.9->1000), concern about care if not on trial (OR12.1; CI 2.1-71.4), pressure to enroll (OR .27; CI 0.12-.64), caregiving without pay (OR 0.13; CI .02-.84). Significant physician beliefs were: patients would not do well on standard therapy (OR 3.6; CI 1.6-8.4), and trial would not be time consuming (OR 3.3; CI 1.3-8.1). CONCLUSIONS: Trial availability, patient and physician beliefs were factors identified that if modified could improve enrollment in cancer cooperative group clinical trials.

Adjuvant chemotherapy for the "oldest old" ovarian cancer patients: can we anticipate toxicity-related treatment failure in a vulnerable population?

BACKGROUND: Patients aged > or = 80 years who are diagnosed with advanced ovarian cancer (OC) have been reported to have a poor prognosis. In the current study, chemotherapy-related toxicity data were evaluated between patients aged > or = 80 years and those aged < 80 years. METHODS: Patients with OC who underwent cytoreductive surgery with chemotherapy were included. Self-reported toxicity data were obtained from National Cancer Institute Common Toxicity Criteria (CTC) forms. Objective indicators of status including albumin level, weight, and creatinine clearance were abstracted both before and after therapy. Data were compared between patients by decade of age. RESULTS: A total of 246 patients were included. A presenting Karnofsky performance status >2 was recorded in 17% of patients aged > or = 80 years versus 0% to 4% of patients aged < 80 years (P = .002). Platinum-based chemotherapy was used in all patients. For patients aged < 80 years, combination chemotherapy was used in > 90% versus 69% in those aged > or = 80 years (P < .0001). Standard-dose combination therapy was used in 72% to 86% of patients aged <80 years versus 28% of patients aged > or =80 years (P < .0001). Patients aged > or =80 years completed > or =6 cycles of therapy approximately 57% of the time versus 84% to 97% of the time for those aged < 80 years (P = .0001). CTC forms identified no self-reported toxicities to be more common among patients aged > or =80 years. Multivariate logistic regression identified creatinine clearance < 65 mL/minute (odds ratio [OR] of 4.6), 5% weight loss (OR of 2.5), prechemotherapy albumin level of < 2 g/dL (OR of 3.65), and initiation of therapy with a single agent (OR of 3.9) as independent predictors of failure to complete chemotherapy. CONCLUSIONS: Despite initial treatment modifications as well as toxicity assessment, only 57% of patients aged > or =80 years completed planned chemotherapy. It was confirmed that further studies into the pharmacokinetics of chemotherapy in the elderly and more sensitive assessment of therapy-related toxicity are required.

Stage IVB endometrial cancer: does applying an ovarian cancer treatment paradigm result in similar outcomes? A case-control analysis.

OBJECTIVE: The pattern of metastasis for Stage IV endometrial carcinoma (EC) is similar to that for ovarian carcinoma (OC), hence the goal of surgical management for both diseases is optimal cytoreduction (CRS) followed by adjuvant chemotherapy. The objective of this study is to evaluate overall survival (OS) and progression-free survival (PFS) in patients with advanced EC compared to a cohort of patients with OC matched for age and residual disease. METHODS: Patients with Stage IVB EC treated with curative intent between the years of 1990-2006 were identified and data abstracted regarding demographics, surgical procedures, pathologic factors, and follow-up. Two patients with Stage IIIC OC were matched for each Stage IVB EC based on age and residual disease. Stage IVB EC patients with distant metastasis were excluded. All OC patients underwent primary CRS and received combination platinum based chemotherapy. PFS and OS were evaluated using Kaplan-Meier curves and log-rank analysis. RESULTS: 55 patients with Stage IVB EC underwent primary CRS and adjuvant therapy with curative intent. Optimal CRS (<1 cm residual disease) was achieved in 87% (n=48). The most common histologic subtypes were serous (53%, n=29), endometrioid (44%, n=24) and clear cell (3%, n=2). Adjuvant therapy with curative intent included platinum based combination chemotherapy (60%, n=33), platinum based chemotherapy with radiation (25%, n=14), and radiation alone (15%, n=8) depending on the time period of treatment. Seven patients had residual disease >1 cm following CRS, 6 of whom received chemotherapy alone. Two-year OS for the entire cohort was 52 vs. 76% for patients with EC compared to OC (p=0.008). For suboptimal EC vs. OC patients was 33% vs. 66% for OC patients (p=NS). EC patients with optimal CRS had OS of 57% at 2 years compared to 82% for OC patients (p=0.02). Median PFS was 13 months vs. 20 months for all EC and OC patients, respectively (p=0.01). Using a Cox proportional hazards model, optimal CRS was associated with a survival advantage over suboptimal for EC patients with a hazard ratio of 2.4. CONCLUSIONS: The treatment paradigm for advanced EC has undergone a drastic evolution from palliation to CRS and combination chemotherapy. Despite similarities in disease distribution and histology, OS for EC patients with intraperitoneal metastasis does not approach that of patients with advanced OC. Further research to identify the molecular characteristics of EC may identify important differences from OC and provide insight for the development of novel primary and salvage treatment strategies for patients with advanced EC.

Ovarian cancer in the octogenarian: does the paradigm of aggressive cytoreductive surgery and chemotherapy still apply?

OBJECTIVE: The cornerstone of therapy for advanced ovarian cancer is cytoreductive surgery (CRS) followed by platinum based chemotherapy. Optimal management for very elderly women (>80) is unclear. This study sought to review the experience with treating ovarian cancer in this population. MATERIALS AND METHODS: This is a retrospective analysis of patients treated between 1991 and 2006. Outcomes included post-operative complications, chemotherapy received and overall survival. Statistical analysis was performed with SAS v.9.1. RESULTS: 85 patients were identified with a mean age of 84 years. 86% of patients presented with advanced disease. Primary CRS was performed on 80%. Among patients with advanced disease who underwent either primary (68) or interval debulking (2), 74% were left with <1 cm residual disease. Post-operative complications were common with 15% of patients suffering cardiac or pulmonary complications, over 10% with prolonged ileus, wound complications or mental status changes and over 30% requiring transfusion or antibiotics. Death prior to hospital discharge and within 60 days of surgery occurred in 13% and 20%. Among patients who underwent CRS, 13% were unable to receive indicated adjuvant therapy. Among those who were treated, 25% were treated with single agent platinum and 43% completed <3 cycles. Two-year overall survival for those who underwent CRS followed by adjuvant therapy is 51%. CONCLUSIONS: Our data suggests that patients >80 may not tolerate combination surgery and chemotherapy. The extremely high proportion of post-operative complications and relatively high proportion of post-operative deaths argues for a more prudent approach to this group of patients.

Intraperitoneal chemotherapy for patients with advanced epithelial ovarian cancer: a review of complications and completion rates.

OBJECTIVE: Intraperitoneal (i.p.) chemotherapy has a clear survival advantage in patients with advanced ovarian cancer, but the high rate of complications has discouraged widespread acceptance. The purpose of this study was to review the completion rate of patients receiving i.p. chemotherapy as first line treatment at a single institution and determine what factors prohibit completion of therapy. METHODS: Patients receiving i.p. chemotherapy from 1993 to 2006 were identified by hospital registries for a retrospective review. Charts were abstracted for patient demographics, clinical and pathologic findings, surgical intervention, treatment modalities, and toxicity. RESULTS: Eighty-three patients were identified who received front line treatment with i.p. chemotherapy. All patients received a platinum and taxane agent. Port placement (single lumen, venous access device) was completed at time of cytoreductive surgery (33%, n=27) or by mini-laparotomy (67%, n=56). Fifty patients (60%) completed a minimum of 6 cycles of treatment with a mean of 5 cycles. Eleven patients (13%) discontinued treatment due to catheter-related complications including infection (n=4), access difficulties (n=3), grade 4 abdominal pain (n=1), port leaking (n=1), and development of a peritoneal-vaginal fistula (n=1). Sixteen patients (19%) did not complete i.p. treatment because of chemotherapy-related toxicity. The remaining six patients did not complete chemotherapy due to disease progression or other reasons unrelated to modality of treatment. CONCLUSIONS: Few catheter-related complications were encountered in a review of front-line i.p. chemotherapy administration at a single institution using a single lumen venous access device. The majority of failures were due to persistent grade 3-4 chemotherapy toxicity. i.p. chemotherapy can be safely administered by a dedicated health-care team committed to i.p. chemotherapy as a front-line treatment.