Oncology Navigation Decreases Time to Treatment in Patients with Pancreatic Malignancy.

BACKGROUND: Care of pancreatic cancer patients has become increasingly complex, which has led to delays in the initiation of therapy. Nurse navigators have been added to care teams, in part, to ameliorate this delay. This study investigated the difference in time from first oncology visit to first treatment date in patients with any pancreatic malignancy before and after the addition of an Oncology Navigator. METHODS: A single-institution database of patients with any pancreatic neoplasm evaluated by a provider in radiation, medical, or surgical oncology between 1 October 2015 and 30 September 2017 was analyzed. After 1 October 2016, an Oncology Navigator met patients at their initial visit and coordinated care throughout treatment. The cohort was divided into two groups: patients evaluated prior to the implementation of an Oncology Navigator and patients evaluated after implementation. Patient demographics and time from first visit to first intervention were compared. RESULTS: Overall, 147 patients with a new diagnosis of pancreatic neoplasm were evaluated; 57 patients were seen prior to the start of the Oncology Navigator program and 79 were evaluated after the navigation program was implemented. On univariate analysis, time from first contact by any provider to intervention was 46 days prior to oncology navigation and 26 days after implementation of oncology navigation (p = 0.005). While controlling for other covariates, employment of the Oncology Navigator decreased the time from first contact by any provider to intervention by almost 16 days (p = 0.009). CONCLUSIONS: Implementing an oncology navigation program significantly decreased time to treatment in patients with pancreatic malignancy.

A Multicenter Randomized Trial to Evaluate Hematologic Toxicities after Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin or Mitomycin in Patients with Appendiceal Tumors.

BACKGROUND: Appendiceal cancer is a rare disease that has proven difficult to study in prospective trials. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established therapy for peritoneal dissemination from appendiceal cancer. The optimal chemotherapeutic agent to use in the HIPEC is not clear. Mitomycin has long been used, however, our previous phase I experience and European retrospective studies suggest oxaliplatin as an alternative. Therefore, we initiated a multicenter randomized trial to compare mitomycin with oxaliplatin HIPEC for appendiceal cancer. STUDY DESIGN: Patients with mucinous appendiceal neoplasms with evidence of peritoneal dissemination underwent cytoreductive surgery and HIPEC using a closed technique for 120 minutes. Patients were randomized intraoperatively to HIPEC using mitomycin (40 mg) or oxaliplatin (200 mg/M2). Follow-up included daily blood counts and toxicity assessments. RESULTS: One hundred and twenty-one analytic patients were accrued to the trial during 6 years at 3 sites. The patients were 57% female, with a mean age of 55.3 years (range 22 to 82 years). The disease was low grade in 77% and high grade in 23%. There were no significant differences in hemoglobin or platelet counts. The WBC was significantly lower in the mitomycin group between postoperative days 5 and 10. Overall and disease-free survival rates at 3 years were similar at 83.7% and 66.8% for mitomycin and 86.9% and 64.8% for oxaliplatin. CONCLUSIONS: This represents the first completed prospective randomized trial for cancer of the appendix, and shows that multicenter trials for this disease are feasible. Both mitomycin and oxaliplatin are associated with minor hematologic toxicity. However, mitomycin has slightly higher hematologic toxicity and lower quality of life than oxaliplatin in HIPEC. Consequently, oxaliplatin might be preferred in patients with leukopenia and mitomycin preferred in patients with thrombocytopenia due to earlier chemotherapy.

Phase II trial of adjuvant oral thalidomide following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal surface disease from colorectal/appendiceal cancer.

PURPOSE: This phase II single-institution trial of adjuvant thalidomide after cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with appendiceal and colorectal malignancies sought to detect an improvement in progression-free survival (PFS) from 7 to 12 months. METHODS: Eligible patients received CS, HIPEC, and baseline imaging, followed by pretreatment thalidomide counseling. All participants were then started on a 28-day regimen of thalidomide, 100 mg by mouth at bedtime, followed by 200 mg for 4 weeks, followed by 300 mg as the final maintenance dose, as tolerated. RESULTS: Twenty-seven eligible patients (median age 52 years; 52% appendiceal/48% colorectal) were enrolled on this trial and included in the analysis, and 26 were evaluable for response. Eighteen patients demonstrated stable disease on adjuvant thalidomide, while eight showed evidence of progression. Approximately 30% of the patients withdrew due to toxicity. Grade 3/4 toxicities included neurological disorders (16%), nausea (12%), vomiting (8%), and thromboembolism (8%). Median overall survival (OS) and PFS were 43.0 and 9.3 months, respectively, and median follow-up was 40.4 months. Multivariate modeling showed significant improvements in PFS and OS for appendiceal patients and those with R0 or R1 resections. On an intent-to-treat analysis, the PFS of the study group was 9 months. CONCLUSIONS: Based on these findings, thalidomide cannot be recommended as adjuvant therapy after CS and HIPEC for gastrointestinal malignancies. Further research is needed to identify active agents in this population.

A phase I trial of oxaliplatin for intraperitoneal hyperthermic chemoperfusion for the treatment of peritoneal surface dissemination from colorectal and appendiceal cancers.

BACKGROUND: Cytoreductive surgery with intraperitoneal hyperthermic chemoperfusion (IPHC) has evolved into a promising approach for peritoneal surface malignancy. A large body of literature suggests that oxaliplatin has excellent cytotoxicity against colorectal cancer. Therefore, we undertook a phase I evaluation of IPHC with oxaliplatin for peritoneal dissemination from colorectal and appendiceal cancers to establish the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). METHODS: Cohorts of three patients underwent cytoreductive surgery followed by a 2-h IPHC with escalating doses of oxaliplatin at a target outflow temperature of 40 degrees C. The initial peritoneal oxaliplatin dose was 200 mg/M(2) with increases planned in 50 mg/M(2 )increments. Plasma and perfusate samples were collected during the IPHC and evaluated using emission spectrometry techniques. Normal tissue and tumor samples were collected before and after the IPHC for analysis. DLT was defined as a grade 3 toxicity lasting 5 days. RESULTS: Fifteen patients were enrolled at two dose levels. Peritoneal fluid areas under the curve (AUCs) were above those of plasma. Additionally, intratumoral oxaliplatin was similar to that of surrounding normal tissue. Dose-limiting toxicities at 250 mg/M(2 )were observed in two of three patients enrolled in this study. CONCLUSION: We found that IPHC with 200 mg/M(2 )of oxaliplatin is well tolerated and is the MTD for a 2-h chemoperfusion. Higher doses are not feasible with this perfusion protocol given the significant toxicities associated with 250 mg/M(2 )oxaliplatin. Based on the data from this phase I study, we propose to conduct further studies with oxaliplatin delivered at 200 mg/M(2).

Monitoring health outcomes following cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for peritoneal carcinomitosis (PC) is an aggressive treatment designed to alleviate symptoms and prolong life. It is associated with physical and psychological morbidity. The purpose of this study was to monitor health outcomes related to treatment. METHODS: Patients completed a questionnaire before and after surgery at 3, 6 and 12 months. The questionnaire consisted of basic demographic items as well as the Functional Assessment of Cancer Therapy-Colon Scale (FACT-C), SF-36 Medical Outcomes Study Health Survey, Center for Epidemiologic Studies-Depression Scale (CES-D), Brief Pain Inventory-Short Form, and ECOG Performance Status Rating. Time trends were assessed with mixed models (SAS PROC MIXED) so as to use all data and to account for missing data. RESULTS: Ninety-six patients (49% females, 9% African Americans) of an average age of 52.9 (SD = 12.5) years were assessed before surgery. PC originated in primary lesions of the appendix (n = 36); colon/rectum (n = 24); mesothelium (n = 9); ovary (n = 5); stomach (n = 4); and miscellaneous (n = 18). Quality of life (QOL) and pain scores improved from baseline to 12 months. Physical functioning changed over the 12-month study period with improvement recorded at 6 months. The percentage of patients reporting significant depressive symptom at each time point was; baseline = 32%; 3 months = 19%; 6 & 12 months = 24%. CONCLUSIONS: Acceptable QOL, return of functional status, and reduced pain can be attained between 3 and 6 months following treatment although some deficits in general health remain. Depressive symptoms are common and should be monitored.