Predicting early mortality in resectable pancreatic adenocarcinoma: A cohort study.

BACKGROUND: Survival after surgical resection for pancreatic cancer remains poor. A subgroup of patients die early (<6 months), and understanding factors associated with early mortality may help to identify high-risk patients. The Khorana score has been shown to be associated with early mortality for patients with solid tumors. In the current study, the authors evaluated the role of this score and other prognostic variables in this setting. METHODS: The current study was a cohort study of patients who underwent surgical resection for pancreatic cancer from January 2006 through June 2013. Baseline (diagnosis ±30 days) parameters were used to define patients as high risk (Khorana score ≥3). Statistically significant univariable associations and a priori prognostic variables were tested in multivariable models; adjusted hazard ratios (HR) were calculated. RESULTS: The study population comprised 334 patients. The median age was 67 years, 50% of the study population was female, and 86% of the patients were white. The pancreatic head was the primary tumor site for 73% of patients; 67% of tumors were T3 and 63% were N1. The median Khorana score was 2; 152 patients (47%) were determined to be high risk. Adjunctive treatment included chemotherapy (70%) and radiotherapy (40%). The postoperative (30-day) mortality rate was 0.9%. The 6-month mortality rate for the entire cohort was 9.4%, with significantly higher rates observed for high-risk patients (13.4% vs 5.6%; P = .02). On multivariable analyses (examining a total of 326 patients), the Khorana score (HR for high risk, 2.31; P = .039) and elevated blood urea nitrogen (HR, 4.34; P<.001) were associated with early mortality. CONCLUSIONS: Patients at high risk of early mortality after surgical resection of pancreatic adenocarcinoma can be identified using simple baseline clinical and laboratory parameters. Future studies should address preoperative interventions in these patients at high risk of early mortality.

Randomized phase I trial of recombinant human keratinocyte growth factor plus chemotherapy: potential role as mucosal protectant.

PURPOSE: To evaluate the safety of recombinant human keratinocyte growth factor (KGF) when administered with fluorouracil (FU) in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Patients (N = 81) received KGF by intravenous (IV) bolus on days 1 to 3, followed by FU 425 mg/m2/d IV bolus plus leucovorin 20 mg/m2/d IV on days 4 to 8. KGF dose levels were 1, 10, 20, 40, 60, and 80 microg/kg/d. A randomized, placebo-controlled design was employed (2:1 randomization of KGF to placebo). Oral mucositis was assessed by examination on days 1, 4, 8, 15, and 28. In addition, patients provided daily assessments of oral symptoms using a self-administered questionnaire. RESULTS: Skin and oral events occurred in 13 of 18 patients (eight patients, grade 1; four patients, grade 2; and one patient, grade 3) treated with 60 and 80 microg/kg of KGF and three of 11 patients treated with 40 microg/kg (grade 1). These symptoms were dose limiting in three cases (ie, in two of 10 patients treated with 80 microg/kg and in one of eight patients treated with 60 microg/kg). The frequency of grade 2 to 4 mucositis was 43% in patients treated with KGF, compared with 67% in patients treated with placebo (P =.06). Patient self-assessments of oral pain and clinical assessments of mucositis showed good correlation (Kendall's tau = 0.75). CONCLUSION: KGF is generally well tolerated when administered IV at doses up to 40 microg/kg/d for 3 days before a 5-day course of FU plus leucovorin. A clinically meaningful biologic effect was also suggested in that patients treated with the epithelial growth factor KGF had a lower rate of grade 2 to 4 mucositis than did patients treated with placebo.

A single institution review of adjuvant therapy outcomes for resectable pancreatic adenocarcinoma: outcome and prognostic indicators.

INTRODUCTION: A large single-institution series of patients who recently underwent pancreaticoduodenectomy for resectable pancreatic cancer was analyzed to determine prognostic factors for overall survival, including the impact of adjuvant radiation and chemotherapy. METHODS: Medical records were reviewed for 179 consecutive patients treated at The Cleveland Clinic with pancreaticoduodenectomy for resectable pancreatic adenocarcinoma from 1999 to 2006. Clinical data were collected, and Kaplan-Meier method was used to estimate overall survival. Univariate and multivariate analysis was performed. RESULTS: One hundred seventy-nine patients with pT1-3N0-1M0 pancreatic cancer met the above criteria. But analysis was available for 158 patients. Median age at diagnosis was 67 (range 35-93). Peri-operative mortality rate was 0.6%. On univariate analysis, poor prognostic factors for overall survival were poorly differentiated histology, lymph node positive disease, elevated alkaline phosphatase, elevated total bilirubin, elevated AST, age at diagnosis >70, and high T stage. On multivariate analysis, poorly differentiated histology (p = .001), age >70 (p = .007), lymph node involvement (> or = 3 positive vs <3, p = .03), and elevated LFTs (alkaline phosphatase and/or bilirubin and/or AST; p = .002) were independent predictors of survival. Median survival for patients treated with adjuvant chemo-XRT was 28.4 months (vs. 11.8 months for patients receiving no adjuvant therapy (p < .001) in both univariate analysis and in multivariate analysis after adjusting for the independent prognostic factors described above). Median survival for patients treated with adjuvant chemotherapy alone had not yet been reached (p < .001 compared to no adjuvant therapy, in both univariate and multivariate analysis). CONCLUSION: In the twenty-first century, curative-intent surgery for pancreatic cancer at large academic institutions can have very low mortality rates. Pathology findings are valuable prognostic markers in resected pancreatic cancer. Few studies have examined the prognostic value of preoperative LFTs or lymph node ratio, and our analysis indicates they may have prognostic value-this should be confirmed in other series. Pts who receive adjuvant therapy (chemo-XRT or chemotherapy) appear to live longer than patients who receive no adjuvant therapy in this retrospective analysis.

Subcutaneous implantable venous access device erosion through the skin in patients treated with anti-vascular endothelial growth factor therapy: a case series.

Subcutaneous implantable venous access devices (IVADs) are commonly used in oncology practice. They facilitate the administration of chemotherapy, fluids and blood products. The incidence of IVAD-related complications is not uncommon, and includes infection, thrombosis and bleeding. IVAD erosion through the skin has been reported secondary to infection or inexperienced handling. We report three cases of IVAD erosion through the skin in patients treated with anti-vascular endothelial growth factor therapy. Anti-vascular endothelial growth factor agents are increasingly used in the treatment of solid tumors. This class of drugs has been associated with delayed wound healing and thromboembolism. To our knowledge, this is the first case series of IVAD erosion through skin, in patients receiving such therapy.

A phase II study of chloroquinoxaline sulfonamide (CQS) in patients with metastatic colorectal carcinoma (MCRC).

PURPOSE: Phase II multicenter study investigated the efficacy and toxicity of the novel halogenated derivative of sulfaquixonaline Chloroquinoxaline Sulfonamide (CQS) in metastatic colorectal cancer. EXPERIMENTAL DESIGN: Eligible patients with metastatic or recurrent colorectal cancer received CQS at a dose schedule of 2000 mg/m2 over an hour weekly for 4 weeks every 42 days. Treatment was continued until unexpected toxicity or disease progression. RESULTS: A total of seventeen patients were enrolled on this study. 94% of all patients enrolled had prior treatment. Sixteen patients were evaluable for response with fifteen patients showing evidence of disease progression and one patient with prolonged stable disease. One patient had non-evaluable disease. Following this interim analysis, the drug was considered ineffective and the study was terminated early. The most frequent adverse event was anemia. No patients discontinued the treatment because of toxicity. CONCLUSION: CQS, when given at a dose of 2000 mg/m2 weekly for 4 weeks every 42 days to patients with metastatic colorectal cancer, does not result in significant tumor regression.