ABSTRACT
The start of the 21st century has produced advances in cancer care that have improved both survival rates and quality of life for many persons diagnosed with cancer. Targeted therapy has given new hope for controlling cancer as a chronic illness. Alone, or in combination with traditional therapies such as surgery, radiation, and/or chemotherapy, this new form of therapy targets malignant cells, halting tumor growth and the potential metastatic spread of disease. Toxicities are limited, but some are serious and may require intensive care. It is imperative for the experienced critical care nurse to have an understanding of these new treatment options and those on the horizon, as these therapies are the future of cancer care. Whereas in previous decades, patients with cancer may not have survived an intensive care admission for treatment complications or advanced disease, many patients now are recovering from life-threatening events, continuing treatment for their disease, and going on to live meaningful, good-quality lives.
Subject(s)
Neoplasms/drug therapy , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Education, Continuing , Humans , Neoplasms/physiopathology , Quality of Life , Survival RateSubject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Aged , Aged, 80 and over , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bevacizumab , Cohort Studies , Dose-Response Relationship, Drug , Female , Humans , Indoles/administration & dosage , Indoles/adverse effects , Male , Middle Aged , Pyrroles/administration & dosage , Pyrroles/adverse effects , SunitinibABSTRACT
PURPOSE: Bevacizumab is an antibody against vascular endothelial growth factor; sunitinib is an inhibitor of vascular endothelial growth factor and related receptors. The safety and maximum tolerated dose of sunitinib plus bevacizumab was assessed in this phase I trial. EXPERIMENTAL DESIGN: Patients with advanced solid tumors were treated on a 3+3 trial design. Patients received sunitinib daily (starting dose level, 25 mg) for 4 weeks on followed by 2 weeks off and bevacizumab (starting dose level, 5 mg/kg) on days 1, 15, and 29 of a 42-day cycle. Dose-limiting toxicities during the first 6-week cycle were used to determine the maximum tolerated dose. RESULTS: Thirty-eight patients were enrolled. Patients received a median of 3 cycles of treatment (range, 1-17(+)). There was one dose-limiting toxicity (grade 4 hypertension) at 37.5 mg sunitinib and 5 mg/kg bevacizumab. Grade 3 or greater toxicity was observed in 87% of patients including hypertension (47%), fatigue (24%), thrombocytopenia (18%), proteinuria (13%), and hand-foot syndrome (13%). Dose modifications and delays were common at higher dose levels. No clinical or laboratory evidence of microangiopathic hemolytic anemia was observed. Seven patients had a confirmed Response Evaluation Criteria in Solid Tumors-defined partial response (18%; 95% confidence interval, 8-34%). Nineteen of the 32 patients with a postbaseline scan (59%) had at least some reduction in overall tumor burden (median, 32%; range, 3-73%). CONCLUSIONS: The combination of sunitinib and bevacizumab in patients with advanced solid tumors is feasible, albeit with toxicity at higher dose levels and requiring dose modification with continued therapy. Antitumor activity was observed across multiple solid tumors.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Indoles/administration & dosage , Neoplasms/drug therapy , Pyrroles/administration & dosage , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab , Dose-Response Relationship, Drug , Female , Humans , Indoles/adverse effects , Male , Maximum Tolerated Dose , Middle Aged , Neoplasms/pathology , Pyrroles/adverse effects , Sunitinib , Treatment Outcome , Tumor Burden/drug effectsABSTRACT
An epidemiological association between cigarette smoking and primary biliary cirrhosis (PBC) has been demonstrated. Our aim was to determine the relationship between smoking and severity of liver fibrosis at presentation in patients with PBC. All patients with PBC seen at the three major teaching hospitals of Case Western Reserve University between October 1998 and December 2005 were identified. Data obtained at the time of the first evaluation leading to the PBC diagnosis on 97 patients were collected. The cumulative number of cigarette packs smoked per year (pack-years) was calculated. Advanced histological disease was defined as Ludwig stages 3 or 4. Analyses were performed to determine associations between advanced histological disease, smoking and other variables related to liver fibrosis. Smoking history was more common (P = .0008) in patients with advanced histological disease at presentation compared to those with early disease. Among smokers, mean lifetime tobacco consumption was higher (P = .04) in cases with advanced histological disease at presentation (30 pack-years) compared to cases with early disease (17 pack-years). Logistic regression demonstrated a significant association between a lifetime tobacco consumption of > or =10 pack-years and advanced histological disease at presentation (OR = 13.3). The association remained significant after adjusting for age, gender, and alcohol intake. The validity of these results was corroborated by cross-validation in an independent confirmatory set of 172 patients with PBC. In conclusion, smoking may accelerate the progression of PBC. This could be induced by exposure to chemicals in cigarette smoke.