Kyong Hwa Park

The cutoff value of serum ferritin for the diagnosis of iron deficiency in community-residing older persons

The serum ferritin assay is the best single blood test for the diagnosis of iron deficiency. Previous studies with elderly anemic patients have suggested that ferritin level less than 45xa0μg/L is indicative of iron deficiency. The subjects of these studies were hospitalized patients with anemia, however. We thus conducted a prospective study to determine the normal minimum level of serum ferritin of community-dwelling older adults by assessing the ratio of serum transferrin receptor to the log ferritin level (sTfR-F index). We conducted the anemia survey between October and November 2002. A total of 1,254 apparently healthy older adults, aged between 60 and 95 years, from three urban community dwellings participated in the survey. Among these individuals, 156 subjects who were anemic or whose serum ferritin level was less than 100xa0μg/L were selected. The soluble transferrin receptor assay was performed and the sTfR-F index was calculated. The receiver operating characteristic curve analysis was performed. Based on the data, serum ferritin level of 22xa0μg/L was selected as the cutoff value for the diagnosis of iron deficiency in community-dwelling older adults. Applying the serum ferritin cutoff of 22xa0μg/L and the sTfR-F index cutoff of 1.5, the sensitivity of the assay was 89.5% (34 of 38) and the specificity was 89.0% (105 of 118). In conclusion, for the diagnosis of iron deficiency of community-residing older adults, we suggest the serum ferritin cutoff value of 22xa0μg/L obtained by use of the sTfR-F index. The value is lower than the previous value established for hospitalized and anemic older adults.

Phase II study with a combination of epirubicin, cisplatin, UFT, and leucovorin in advanced hepatocellular carcinoma

Purpose: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Because HCC usually presents as an advanced disease and occurs in the background of liver cirrhosis, most patients are not suitable for treatment with curative intent, thus effective systemic chemotherapy is required. However, the outcome of systemic chemotherapy has been disappointing in advanced HCC. This study was conducted to test the efficacy and toxicity of the combined regimen of epirubicin, cisplatin, and UFT moderated by leucovorin in advanced or recurrent HCC. Patients and methods: All 53 patients received epirubicin (50xa0mg/m2 i.v.) on day 1 and cisplatin (60xa0mg/m2 i.v.) after epirubicin administration. Oral UFT 400–600xa0mg/day, determined by body surface area, and leucovorin 75xa0mg/day were administered for 21 consecutive days, followed by a 7-day drug free interval. Results: Nine had a partial response, representing 16.9% of response rate (95% confidence interval rate; 7.0–26.8%) with median response duration of 17.1xa0weeks (95% CI; 5.0–29.3xa0weeks, range; 7.1–51.7xa0weeks). Fifteen patients had stable disease and the disease progressed in 26 patients. The median overall survival for the patients was 24.6xa0weeks (95% CI; 17.3–31.9xa0weeks, range; 3.0–131.3xa0weeks). The main toxicities were hematologic toxicities including neutropenia, which reached grade 3/4 in 17 patients (38.5%), and grade 3 or 4 thrombocytopenia in five patients (9.4%). Conclusion: The combination of epirubicin, cisplatin, and UFT moderated by leucovorin showed modest anti-tumor activity with relatively tolerable toxicities. However, a randomized phase III trial based on this regimen is warranted to clarify its survival benefit in patients with advanced HCC.

Mitomycin‐C, 5‐fluorouracil, and leucovorin as a salvage therapy in patients with metastatic colorectal adenocarcinoma

Aim:u2003 There is no further treatment option for metastatic colon patients who are refractory to standard chemotherapy and to whom novel biological agents are not available. We evaluated the outcomes of mitomycin‐C, 5‐fluorouracil (5‐FU) and leucovorin in patients with metastatic colon cancer previously treated with oxaliplatin/5‐FU/leucovorin and irinotecan/5‐FU/leucovorin.

A randomized phase II trial of ridaforolimus, dalotuzumab, and exemestane compared with ridaforolimus and exemestane in patients with advanced breast cancer

PurposeTo evaluate whether adding humanized monoclonal insulin growth factor-1 receptor (IGF-1R) antibody (dalotuzumab) to mammalian target of rapamycin (mTOR) inhibitor (ridaforolimus) plus aromatase inhibitor (exemestane) improves outcomes in patients with estrogen receptor (ER)-positive advanced/metastatic breast cancer.MethodsThis randomized, open-label, phase II trial enrolled 80 postmenopausal women with high-proliferation (Ki67 index stainingxa0≥15%), ER-positive breast cancer that progressed after a non-steroidal aromatase inhibitor (NCT01605396). Randomly assigned patients were given oral ridaforolimus 10xa0mg QD 5xa0×/week, intravenous dalotuzumab 10xa0mg/kg/week, and oral exemestane 25xa0mg/day (R/D/E, nxa0=xa040), or ridaforolimus 30xa0mg QD 5xa0×/week and exemestane 25xa0mg/day (R/E; nxa0=xa040). Primary end point was progression-free survival (PFS).ResultsMedian PFS was 23.3xa0weeks for R/D/E versus 31.9xa0weeks for R/E (hazard ratio 1.18; 80% CI 0.81–1.72; Pxa0=xa00.565). Grade 3–5 adverse events were reported in 67.5% of patients in the R/E arm and 59.0% in the R/D/E arm. Stomatitis (95.0 vs. 76.9%; Pxa0=xa00.021) and pneumonitis (22.5 vs. 5.1%; Pxa0=xa00.027) occurred more frequently in the R/E than the R/D/E arm; hyperglycemia (27.5 vs. 28.2%) occurred at a similar rate.ConclusionsR/D/E did not improve PFS compared with R/E. Because the PFS reported for R/E was similar to that reported for everolimus plus exemestane in patients with advanced breast cancer, it is possible that lower-dose ridaforolimus in the R/D/E arm (from overlapping toxicities with IGF1R inhibitor) contributed to lack of improved PFS.

Capecitabine monotherapy as salvage treatment after failure of chemotherapy containing oxaliplatin and irinotecan in patients with metastatic colorectal cancer

Aim:u2003 There has been limited data on capecitabine monotherapy in metastatic colorectal cancer (CRC) patients who were previously treated with both oxaliplatin/5‐fluorouracil(FU)/leucovorin (FOLFOX) and irinotecan/5‐FU/leucovorin (FOLFIRI).

Prevalence of iron deficiency anemia in community-dwelling older persons as measured by the transferrin receptor-ferritin index

community-dwelling older adults using the sTfR-F index. We conducted the anemia survey in three urban districts (Guro, Yangcheon and Gwanak) located in the southwestern part of Seoul in 2002. In this survey, a total of 1,254 subjects over the age of 60 years were selected from a cross-sectional study, the results of which have been published previously [2] . In brief, all the subjects lived in their own homes and were fully ambulatory with unlimited activities of daily living. Informed consent was obtained from all subjects, and then a complete medical history was taken and laboratory testing including a complete blood cell count with a reticulocyte count and iron profi les was performed. Anemia was defi ned according to the World Health Organization criteria, i.e. a hemoglobin level of ! 13 g/dl in men and ! 12 g/dl in women. In case of anemia, we performed the sTfR assay using a commercial kit based on a polyclonal antibody in a sandwich enzyme immunoassay (R&D Systems, Minneapolis, Minn., USA). According to the manufacturer, the central 95th percentile of the reference distribution of the sTfR concentration is 8.7–28.1 nmol/l. We then calculated the sTfR-F index (ratio of sTfR and log ferritin level). All the sTfR assays were performed in duplicate. IDA was considered present if the subject had anemia and the sTfR-F index was 1 1.5. Anemia is the most common hematologic problem encountered in older adults, and its prevalence increases with age [1, 2] . The common causes of anemia among older persons are anemia of chronic disease, iron defi ciency caused by gastrointestinal bleeding, cobalamin defi ciency, folate defi ciency and the myelodysplasia. Among these causes, the diagnosis of iron defi ciency anemia (IDA) is important because proper iron therapy can improve the symptoms, and treatment may help indicate an occult gastrointestinal pathology such as malignancy [3, 4] . There are few reports regarding the prevalence of IDA in older persons, and epidemiologic studies on East Asian populations are scarce. Moreover, the results of such studies have been variable according to the diagnostic criteria used. Previously published reports have used serum ferritin levels to diagnose IDA, but the cutoff levels were different in the various studies. The interpretation of the serum ferritin level in older adults is sometimes complicated because its level increases with age and with concomitant chronic illnesses [5, 6] . Therefore, we measured the soluble transferrin receptor (sTfR), which is not infl uenced by ageing or chronic diseases [7, 8] , and we calculated the ratio of sTfR to the log ferritin level (sTfR-F index) to make the test more specifi c. An index value of