Management of malignancy-related ascites.

A 65-year-old Polish immigrant named T. J. was diagnosed with metastatic colon cancer in January 2012 when he presented with obstructing sigmoid colon cancer and liver metastases. A diverting colostomy as well as biopsy of his liver metastases was performed and chemotherapy with FOLFOX (5-fluorouracil [5-FU], leucovorin, oxaliplatin) and bevacizumab was initiated. After three months, he transitioned to maintenance therapy with infusional 5-FU and bevacizumab until he progressed in August 2012. Oxaliplatin was reintroduced and he responded until he developed progressive neuropathy in November and his therapy was changed to FOLFIRI (5-FU, leucovorin, irinotecan) and bevacizumab. T. J. developed liver progression after three months and, because he was Kras wild type, irinotecan and panitumumab were initiated. Liver-directed therapy also was pursued and he underwent radioembolization with yittrium-90 followed by chemoembolization with irinotecan-eluded beads. At the time of these procedures, T. J.'s portal and hepatic venous systems were patent (i.e., no thrombosis or obstruction causing portal hypertension).

Carcinoid heart disease.

The patient, C.P., is a 59-year-old woman who was diagnosed with metastatic carcinoid of the terminal ileum in May 2003. In June 2003, she underwent an extensive resection including hemicolectomy, cholecystectomy, distal pancreatectomy, and splenectomy with metastatic disease in her pancreas, mesentery, and liver. She had been treated with octreotide, everolimus, oxaliplatin, and multiple hepatic artery embolizations in the past eight years and, most recently, capecitabine and bevacizumab with monthly octreotide. She has had intermittent pleural effusions not requiring intervention and a trace pericardial effusion. Her tumor is functional, meaning it demonstrates hormonal hypersecretion which causes flushing, diarrhea, bronchospasm, and abdominal pain.

Historical perspective on the progress of chemotherapy-induced nausea and vomiting treatment in oncology nursing forum.

Chemotherapy-induced nausea and vomiting (CINV) has been a priority symptom in the management of patients with cancer since the inception of chemotherapy. In the mid-1970s, the most effective agents available were the standard antiemetics used for gastrointestinal illnesses, postoperative nausea, and morning sickness. The Oncology Nursing Forum has documented the study of this symptom­causes, pathophysiology, and manifestations­in the past four decades as well as emerging treatment therapies. To date, CINV is fairly well controlled, but work still needs to be done, particularly in delayed and refractory management.

Phase II study of everolimus in metastatic urothelial cancer.

UNLABELLED: What's known on the subject? and what does the study add?: No recent advances have been made in the treatment of patients with advanced bladder cancer and, to date, targeted therapies have not resulted in an improvement in outcome. The mammalian target of rapamycin pathway has been shown to be up-regulated in bladder cancer and represents a rational target for therapeutic intervention. In the present phase II study of everolimus, one near-complete response, one partial response and several minor responses suggest that everolimus possesses biological activity in a subset of patients with bladder cancer. To maximize benefit from targeted agents such as everolimus, the preselection of patients based on molecular phenotype is required. OBJECTIVE: To assess the efficacy and tolerability of everolimus in advanced urothelial carcimoma (UC). PATIENTS AND METHODS: The present study comprised a single-arm, non-randomized study in which all patients received everolimus 10 mg orally once daily continuously (one cycle = 4 weeks). In total, 45 patients with metastatic UC progressing after one to four cytotoxic agents were enrolled between February 2009 and November 2010 at the Memorial Sloan-Kettering Cancer Center. The primary endpoints were 2-month progression-free survival (PFS) and the safety of everolimus, with the secondary endpoint being the response rate. A Simon minimax two-stage design tested the null hypothesis that the true two month PFS rate was ≤ 50%, as opposed to the alternative hypothesis of ≥ 70%. RESULTS: The most common grade 3/4 toxicities were fatigue, infection, anaemia, lymphopaenia, hyperglycaemia and hypophosphataemia. There were two partial responses in nodal metastases, with one patient achieving a 94% decrease in target lesions and remaining on drug at 26 months. An additional 12 patients exhibited minor tumour regression. There were 23 of 45 (51%) patients who were progression-free at 2 months with a median (95% CI) PFS of 2.6 (1.8-3.5) months and a median (95% CI) overall survival of 8.3 (5.5-12.1) months. No clear association was observed between mammalian target of rapamycin pathway marker expression and 2-month PFS. CONCLUSIONS: Although everolimus did not meet its primary endpoint, one partial response, one near-complete response and twelve minor regressions were observed. Everolimus possesses meaningful anti-tumour activity in a subset of patients with advanced UC. Studies aiming to define the genetic basis of everolimus activity in individual responders are ongoing.

Antiemetics: American Society of Clinical Oncology clinical practice guideline update.

PURPOSE: To update the American Society of Clinical Oncology (ASCO) guideline for antiemetics in oncology. METHODS: A systematic review of the medical literature was completed to inform this update. MEDLINE, the Cochrane Collaboration Library, and meeting materials from ASCO and the Multinational Association for Supportive Care in Cancer were all searched. Primary outcomes of interest were complete response and rates of any vomiting or nausea. RESULTS: Thirty-seven trials met prespecified inclusion and exclusion criteria for this systematic review. Two systematic reviews from the Cochrane Collaboration were identified; one surveyed the pediatric literature. The other compared the relative efficacy of the 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonists. RECOMMENDATIONS: Combined anthracycline and cyclophosphamide regimens were reclassified as highly emetic. Patients who receive this combination or any highly emetic agents should receive a 5-HT(3) receptor antagonist, dexamethasone, and a neurokinin 1 (NK(1)) receptor antagonist. A large trial validated the equivalency of fosaprepitant, a single-day intravenous formulation, with aprepitant; either therapy is appropriate. Preferential use of palonosetron is recommended for moderate emetic risk regimens, combined with dexamethasone. For low-risk agents, patients can be offered dexamethasone before the first dose of chemotherapy. Patients undergoing high emetic risk radiation therapy should receive a 5-HT(3) receptor antagonist before each fraction and for 24 hours after treatment and may receive a 5-day course of dexamethasone during fractions 1 to 5. The Update Committee noted the importance of continued symptom monitoring throughout therapy. Clinicians underestimate the incidence of nausea, which is not as well controlled as emesis.

Sunitinib in urothelial cancer: clinical, pharmacokinetic, and immunohistochemical study of predictors of response.

BACKGROUND: Sunitinib has activity in patients with metastatic urothelial cancer (UC), but most patients do not respond. OBJECTIVE: To identify predictors of response to sunitinib. DESIGN, SETTING, AND PARTICIPANTS: Seventy-seven patients with advanced UC received sunitinib on one of two schedules at a single institution. Blood pressure (BP), immunohistochemistry (IHC), and pharmacokinetic (PK) results were correlated with response to sunitinib. MEASUREMENTS: BP was assessed on day 1 and 28 of each cycle and on day 14 of cycle 1. IHC was performed on 55 samples from 38 cases using mammalian target of rapamycin and hypoxia-inducible factor (HIF) pathway marker antibodies. Blood samples for PK analysis were collected from 15 patients at three time points. Response was assessed using Response Evaluation Criteria in Solid Tumors criteria. RESULTS AND LIMITATIONS: Sunitinib-induced hypertension predicted improved response when hypertension was categorized as a discrete (p = 0.02) or continuous variable (p = 0.005 [systolic BP] and p = 0.007 [diastolic BP]). The odds ratio of response was 12.5 (95% confidence interval, 1.95-246.8) for grade 3/4 hypertension compared with grade 0. Response was associated with low HIF-1α expression in primary (p = 0.07) tissue. A nonstatistically significant trend was seen for an association between greater drug concentration and best response. A correlation between expression markers within the same pathways was identified, phosphorylated-4EBP1 and phosphorylated-S6 (p = 6.5 × 10(-9)), and vascular endothelial growth factor receptor 2 and HIF-1α (p = 0.008). Results are limited by small numbers. CONCLUSIONS: Clinical and molecular biomarkers of response to sunitinib may have clinical relevance and require prospective validation. There is an urgent need for predictive biomarkers to guide the management of UC.

Phase II study of sunitinib in patients with metastatic urothelial cancer.

PURPOSE: No standard therapy exists for metastatic urothelial cancer (UC) that has progressed after initial chemotherapy. This trial was designed to assess the efficacy and tolerability of sunitinib in patients with advanced, previously treated UC. PATIENTS AND METHODS: In this phase II trial, 77 patients received sunitinib between September 2006 and January 2009 on one of two schedules (50 mg per day for 4 weeks on and 2 weeks off [cohort A], 37.5 mg per day continuously [cohort B]), using a Simon 2 stage design in each cohort separately. RESULTS: A partial response was seen in three of 45 patients (95% CI, 1% to 18%) in cohort A, and in one of 32 patients (95% CI, 0% to 16%) in cohort B. Clinical regression or stable disease was achieved in 33 of 77 patients (43%). Tumor regression lasted between 0.6 and 23.4 months with 29% of patients achieving response lasting longer than 3 months. The progression-free survival (2.4 v 2.3 months; P = .4) and overall survival (7.1 v 6.0 months; P = .4) were similar in both cohorts. There was one treatment-related death, and 47 patients (33 cohort A, 24 cohort B) experienced grade 3 or 4 toxicity. CONCLUSION: Sunitinib did not achieve the predetermined threshold of >or= 20% activity defined by Response Evaluation Criteria in Solid Tumors. However, antitumor responses were observed, identifying the vascular endothelial growth factor axis as a viable pathway for UC treatment. The reported clinical benefit in previously treated patients warrants further investigation in a disease for which there is no US Food and Drug Administration-approved treatment.