Bilaterally enlarged adrenal glands without obvious cause: need for a multidisciplinary diagnostic work-up.

Bilateral enlarged adrenal glands are rare, and as diagnostic delay may have serious consequences for the patient, we recommend a multidisciplinary approach of specialists in the field of endocrinology, oncology, radiology, and clinical chemistry prior to the start of the diagnostic work-up.

Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders.

Non-transferrin-bound iron and its labile (redox active) plasma iron component are thought to be potentially toxic forms of iron originally identified in the serum of patients with iron overload. We compared ten worldwide leading assays (6 for non-transferrin-bound iron and 4 for labile plasma iron) as part of an international inter-laboratory study. Serum samples from 60 patients with four different iron-overload disorders in various treatment phases were coded and sent in duplicate for analysis to five different laboratories worldwide. Some laboratories provided multiple assays. Overall, highest assay levels were observed for patients with untreated hereditary hemochromatosis and ß-thalassemia intermedia, patients with transfusion-dependent myelodysplastic syndromes and patients with transfusion-dependent and chelated ß-thalassemia major. Absolute levels differed considerably between assays and were lower for labile plasma iron than for non-transferrin-bound iron. Four assays also reported negative values. Assays were reproducible with high between-sample and low within-sample variation. Assays correlated and correlations were highest within the group of non-transferrin-bound iron assays and within that of labile plasma iron assays. Increased transferrin saturation, but not ferritin, was a good indicator of the presence of forms of circulating non-transferrin-bound iron. The possibility of using non-transferrin-bound iron and labile plasma iron measures as clinical indicators of overt iron overload and/or of treatment efficacy would largely depend on the rigorous validation and standardization of assays.

Cost effectiveness of primary pegfilgrastim prophylaxis in patients with breast cancer at risk of febrile neutropenia.

PURPOSE: Guidelines advise primary granulocyte colony-stimulating factor (G-CSF) prophylaxis during chemotherapy if risk of febrile neutropenia (FN) is more than 20%, but this comes with considerable costs. We investigated the incremental costs and effects between two treatment strategies of primary pegfilgrastim prophylaxis. METHODS: Our economic evaluation used a health care perspective and was based on a randomized study in patients with breast cancer with increased risk of FN, comparing primary G-CSF prophylaxis throughout all chemotherapy cycles (G-CSF 1-6 cycles) with prophylaxis during the first two cycles only (G-CSF 1-2 cycles). Primary outcome was cost effectiveness expressed as costs per patient with episodes of FN prevented. RESULTS: The incidence of FN increased from 10% in the G-CSF 1 to 6 cycles study arm (eight of 84 patients) to 36% in the G-CSF 1 to 2 cycles study arm (30 of 83 patients), whereas the mean total costs decreased from € 20,658 (95% CI, € 20,049 to € 21,247) to € 17,168 (95% CI € 16,239 to € 18,029) per patient, respectively. Chemotherapy and G-CSF determined 80% of the total costs. As expected, FN-related costs were higher in the G-CSF 1 to 2 cycles arm. The incremental cost effectiveness ratio for the G-CSF 1 to 6 cycles arm compared with the G-CSF 1 to 2 cycles arm was € 13,112 per patient with episodes of FN prevented. CONCLUSION: We conclude that G-CSF prophylaxis throughout all chemotherapy cycles is more effective, but more costly, compared with prophylaxis limited to the first two cycles. Whether G-CSF prophylaxis throughout all chemotherapy cycles is considered cost effective depends on the willingness to pay per patient with episodes of FN prevented.

Primary granulocyte colony-stimulating factor prophylaxis during the first two cycles only or throughout all chemotherapy cycles in patients with breast cancer at risk for febrile neutropenia.

PURPOSE: Early breast cancer is commonly treated with anthracyclines and taxanes. However, combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor (G-CSF) support. The highest incidence of febrile neutropenia (FN) and largest benefit of G-CSF during the first cycles of chemotherapy lead to questions about the effectiveness of continued use of G-CSF throughout later cycles of chemotherapy. PATIENTS AND METHODS: In a multicenter study, patients with breast cancer who were considered fit enough to receive 3-weekly polychemotherapy, but also had > 20% risk for FN, were randomly assigned to primary G-CSF prophylaxis during the first two chemotherapy cycles only (experimental arm) or to primary G-CSF prophylaxis throughout all chemotherapy cycles (standard arm). The noninferiority hypothesis was that the incidence of FN would be maximally 7.5% higher in the experimental compared with the standard arm. RESULTS: After inclusion of 167 eligible patients, the independent data monitoring committee advised premature study closure. Of 84 patients randomly assigned to G-CSF throughout all chemotherapy cycles, eight (10%) experienced an episode of FN. In contrast, of 83 patients randomly assigned to G-CSF during the first two cycles only, 30 (36%) had an FN episode (95% CI, 0.13 to 0.54), with a peak incidence of 24% in the third cycle (ie, first cycle without G-CSF prophylaxis). CONCLUSION: In patients with early breast cancer at high risk for FN, continued use of primary G-CSF prophylaxis during all chemotherapy cycles is of clinical relevance and thus cannot be abandoned.

Fatal necrotizing pancreatitis during combined treatment with erlotinib and sunitinib.

With the increased use of tyrosine kinase inhibitors as successful therapy in selected malignancies, their adverse effects will grow, especially when combination therapy is used. We present a relatively young patient who was successfully treated with erlotinib and sunitinib for her metastatic non-small-cell lung cancer (NSCLC), but died because of the serious event of a necrotizing pancreatitis with severe hypocalcaemia, which we suppose to be an adverse event of the therapy used.

Cost analysis of common treatment options for indolent follicular non-Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: We assessed direct health care costs associated with the most commonly prescribed treatments for indolent follicular non-Hodgkin's lymphoma (FL). DESIGN AND METHODS: New and previously diagnosed FL patients (>or=18 years) known during 1997-1998 to 15 Dutch hospitals were selected for inclusion. Each patient was followed for 3 years, and resource use associated with each of the treatments, including watchful waiting, was recorded. The hospital perspective was adopted. Unit costs were based on 2003 price levels. RESULTS: Two hundred patients were included of whom 75% underwent one or more treatments during the 3-year data collection period [25% were not treated because of a watchful waiting strategy (10%) or complete remission (15%)]. Allogeneic and autologous stem cell transplantations were the most expensive treatments, with a mean (median) per patient cost of 45,326 euro(44,237; n=7) and 18,866 euro (16,532; n=9), respectively (up to discharge only). Intravenous fludarabine cost 10,651 euro (9,995; n=33), rituximab (10,628 euro; 10,124; n=7), and CHOP 7,547 euro (5,833; n=42). Classical FL treatments were found to be the least expensive treatments used with an estimated cost for cylophosphamide, vincristine and prednisone of 5,268 euro (2,644; n=58), for radiotherapy of 4,218 euro (4,313; n=52), and for chlorambucil of 2,476 euro (1,098; n=53). INTERPRETATION AND CONCLUSIONS: This study presents information on resource use and costs associated with the most commonly prescribed FL treatments. In addition to differences in effectiveness, commonly used treatments vary considerably in terms of resource use and overall cost. This information is of value for resource planning, given the high costs of new treatment modalities.