So Young Yoon

Validation of the Edmonton Symptom Assessment System in Korean Patients With Cancer

CONTEXT The Edmonton Symptom Assessment System (ESAS) is a brief, widely adopted, multidimensional questionnaire to evaluate patient-reported symptoms. OBJECTIVES To develop a Korean version of the ESAS (K-ESAS) and to perform a psychometric analysis in Korean patients with advanced cancer. METHODS We tested the K-ESAS in two pilot studies with 15 patients each. We assessed internal consistency, test-retest reliability, and concurrent validity in 163 Korean patients, who completed the K-ESAS along with the Korean versions of the M. D. Anderson Symptom Inventory (K-MDASI) and the Hospital Anxiety and Depression Scale (K-HADS) twice. A total of 38 patients completed the questionnaires again seven days later to assess responsiveness. RESULTS The K-ESAS scores had good internal consistency, with a Cronbachs alpha coefficient of 0.88, indicating that no questions had undue influence on the score. Pearson correlation coefficients for K-ESAS symptom scores between baseline and after two to four hours ranged from 0.72 (95% CI 0.64-0.79) to 0.87 (95% CI 0.82-0.90), indicating strong test-retest reliability. For concurrent validity, Pearson correlation coefficients between K-ESAS symptom scores and corresponding K-MDASI symptom scores ranged from 0.70 (95% CI 0.62-0.77) to 0.83 (95% CI 0.77-0.87), indicating good concurrent validity. For the K-HADS, concurrent validity was good for anxiety (r=0.73, 95% CI 0.65-0.79) but moderate for depression (r=0.4, 95% CI 0.26-0.52). For responsiveness, changes in K-ESAS scores after seven days were moderately correlated with changes in K-MDASI scores but weakly correlated with changes in K-HADS scores. CONCLUSION The K-ESAS is a valid and reliable tool for measuring multidimensional symptoms in Korean patients with cancer.

Serum prohepcidin levels in Helicobacter pylori infected patients with iron deficiency anemia.

Background/Aims Helicobacter pylori (H. pylori) infection appears to subvert the human iron regulatory mechanism and thus upregulates hepcidin, resulting in unexplained iron-deficiency anemia (IDA). We evaluated serum prohepcidin levels before and after eradication of H. pylori in IDA patients to assess whether it plays a role in IDA related to H. pylori infection. Methods Subjects diagnosed with unexplained IDA underwent upper gastrointestinal endoscopy and colonoscopy to confirm H. pylori infection and to exclude gastrointestinal bleeding. Blood was sampled before treatment to eradicate H. pylori and again 1 month later. Serum prohepcidin levels were measured using a commercial enzyme-linked immunosorbent assay kit. Results Serum prohepcidin levels decreased significantly after oral iron replacement combined with H. pylori eradication (p = 0.011). The reduction ratio of serum prohepcidin levels after the treatment did not differ among the combined oral iron replacement and H. pylori eradication groups, the H. pylori eradication only group, and the iron replacement only group (p = 0.894). Conclusions Serum prohepcidin levels decrease after both H. pylori eradication and oral iron administration, with improvement in IDA. Serum concentration of prohepcidin is related to the anemia status, rather than to the current status of H. pylori infection, in IDA patients.

An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer

Purpose Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). Materials and Methods Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). Results The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m2 (95.0%), and that of Genexol was 168.3±10.6 mg/m2 (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (pnon-inferiority=0.021, psuperiority=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. Conclusion Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.

Pilot Study of Heptaplatin, UFT-E and Leucovorin in Advanced Gastric Carcinoma

PURPOSE Heptaplatin (SKI-2053R, Sunpla ), a new platinum analogue which has a better toxicity profile than cisplatin, has been used with 5-fluorouracil (5-FU) continuous infusion for the treatment of advanced gastric carcinoma. However, continuous 5-FU infusion had a inconvenience to administration. The aim of this study was to evaluate the efficacy and toxicity of heptaplatin, UFT-E and leucovorin combination chemotherapy in advanced gastric cancer. MATERIALS AND METHODS A total of 22 patients was enrolled in this study at Kyung Hee University and Korea University from September 1999 to May 2001. Heptaplatin 400 mg/m2 was given as intravenous infusion for 1 hour at day 1. Oral UFT-E 360 mg/m2 and leucovorin 45 mg/day were administered for 21 consecutive days followed by a 7-day drug free interval. This schedule was repeated every 4 weeks. RESULTS The 22 enrolled patients received 81 courses of chemotherapy and the median number of course per patient was three with a range of one to six. Five of 21 patients achieved partial responses (23.8%; 95% confidence interval, 5.6% to 42%) without complete response. Out of the 5 responding patients, three had unresectable perigastric lymph-nodes, one patient had a ovarian metastasis, and one patient had a peritoneal metastasis respectively. Main toxicities were neutropenia and nausea/vomiting. Grade 3 and 4 neutropenia were observed in 4 patients (18%) and grade 3 nausea/vomiting were observed in 5 patients (22.7%). The median time to progression was 4 months (range, 0.5 to 13 months), and median survival duration was 7.5 months (range, 2.0 to 14 months). Median response duration was 5.0 months (range, 1.5 to 10 months). CONCLUSION A combination chemotherapy of heptaplatin, UFT-E and leucovorin has a comparable efficacy with those of previously reported heptaplatin and intravenous regimen of 5-FU and controllable toxicity in advanced gastric carcinoma. Further study with large patient population is warranted to determine the usefulness of this regimen.

Hepatic Metastases of Gastric Adenocarcinoma Showing Metabolic Remission on FDG-PET Despite an Increase in Size on CT

We report a gastric adenocarcinoma patient with liver metastases. The metastases showed progression on computed tomography (CT), but this was not true progression in terms of metabolic activity according to (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET). Discordance between size criteria and metabolic criteria has been reported in liver gastrointestinal stromal tumors, hepatomas, and renal cell carcinomas after dramatic responses with targeted therapies such as imatinib, sorafenib, and sunitinib (1-6). However, this discordance has been rarely reported in liver metastases of gastric adenocarcinoma when treated with conventional chemotherapy.

Acute cor pulmonale due to pulmonary tumor thrombotic microangiopathy in two patients with breast cancer

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Irinotecan Monotherapy Versus Irinotecan-Based Combination as Second-Line Chemotherapy in Advanced Gastric Cancer: A Meta-Analysis

Purpose A meta-analysis was conducted to examine the question of whether combination regimens are more effective than monotherapy as a second-line chemotherapy in advanced gastric cancer. Materials and Methods The MEDLINE and the EMBASE databases and the Cochrane Central Register for Controlled Trials were searched using appropriate keywords. Only randomized controlled trials were eligible. Results Taxane-based study is rare; thus, four irinotecan-based studies were finally included in the meta-analysis. Out of 661 patients, 331 patients were assigned to combination therapy and 330 to monotherapy. Cisplatin or fluoropyrimidine (S-1 or 5-fluorouracil) was used as a combination partner to irinotecan. The pooled hazard ratio (HR) for overall survival (OS) and for progression-free survival (PFS) was 0.938 (95% confidence interval [CI], 0.796 to 1.104; p=0.442) and 0.815 (95% CI, 0.693 to 0.958; p=0.013). In subgroup analysis according to previous exposure to a partner agent, the PFS benefit of combination was observed only in the partially exposed group (HR, 0.784; 95% CI, 0.628 to 0.980; p=0.032). Conclusion Second-line irinotecan-based combination was not associated with increased OS, but with PFS benefit, which seemed particularly significant for patients receiving combination with a new agent.

Successful allogeneic stem-cell transplantation in a patient with myelodysplastic syndrome with hemodialysis-dependent end-stage renal disease.

Despite the use of a reducedintensity conditioning regimen for recipients of allogeneic stem-cell transplantation (allo-SCT) with renal impairment, patients with end-stage renal disease (ESRD) who require dialysis have been excluded from allo-SCT because of high risk of transplant-related death. Therefore, only a few cases of allo-SCT in patients with nonmalignant hematologic disease who are on dialysis have been reported (1– 4), and no case of successful allo-SCT in malignant patients on dialysis has been reported, even in patients with myeloma-associated ESRD. The reason is that the risk of transplantrelated mortality in allo-SCT is expected to be much higher for malignant hematologic disease, compared with nonmalignant disease, even in patients with normal renal function. A 61-year-old man with ESRD caused by diabetic nephropathy was referred to the hematology department with pancytopenia requiring regular transfusional support every 2 weeks. He had been on hemodialysis (HD) for 5 years. Bone marrow examination revealed 7% blasts and three-lineage dysplasia, which led to a diagnosis of refractory anemia with excess blasts-1. The karyotype of bone marrow cells was 46XY. Based on the World Health Organization–adapted prognostic scoring system of myelodysplastic syndrome, he was in a high-risk group. The patient received six cycles of decitabine treatment; however, there was no response. He underwent alloSCT from a mismatched (one allele and one antigen-mismatched) unrelated donor. The conditioning regimens were fludarabine (15 mg/m/day for 5 days), melphalan (50 mg/m/day for 2 days), and total body irradiation (400 cGy). Antithymocyte globulin (1.25 mg/kg/day for 2 days) was given before transplantation for prophylaxis of acute graft-versushost disease (GvHD). Doses of fludarabine and melphalan were adjusted based on previous experimental reports (5–7). During the conditioning period, daily HD was performed for volume control. The stem-cell source was granulocyte colony stimulating factor-mobilized peripheral blood stem cells. The amount of infused CD34-positive cells was 8.99 10 54 /kg and that of CD3-positive cells was 37 10 54 /kg. Tacrolimus and mycophenolate mofetil were used for GvHD prophylaxis. For prevention of infection, acyclovir, micafungin, and sulfamethoxazole/trimethoprim were prescribed. The engraftment was successful. Neutrophil and platelet count showed recovery at day 12 posttransplant, and donor chimerism measured using polymerase chain reaction (PCR) analysis of short tandem repeat sequences in bone marrow cells at day 22 posttransplant revealed 100% of donor type. However, the posttransplant clinical course was complicated. On the 12th day posttransplant, sinusoidal obstruction syndrome developed and total bilirubin level was increased up to 8.1 mg/dL. Mycophenolate mofetil was discontinued, and recombinant tissue plasminogen activator was administered. The sinusoidal obstruction syndrome was resolved with a 4-day treatment of recombinant tissue plasminogen activator. From day 15 posttransplant, grade III gut GvHD developed; however, it was resolved with methyl prednisolone treatment. After discharge, he was admitted to the hospital three times because of recurrent diarrhea. The gut GvHD was steroidrespondent but dependent at the first two admissions; however, it became steroid-resistant at the third admission. Only after treatment with antithymocyte globulin, the steroid-resistant GvHD was resolved. Two weeks after resolution of diarrhea, fever and pancytopenia developed. Bone marrow biopsy revealed active hemophagocytosis, and quantitative PCR for Epstein-Barr virus (EBV) indicated a high load of EBV DNA in bone marrow cells. PCR for short tandem repeat was 100% of donor type in bone marrow cells.Immunosuppressant was tapered off for EBV-associated hemophagocytosis, and the complete blood count showed a slow recovery. He is still alive and disease free without transfusional support, maintaining full donor chimerism. This is the first reported case of successful allo-SCT of a dialysis patient with malignant hematologic disease. Overor underdosing of conditioning regimens may result in the death of those patients owing to unacceptable regimen-related toxicity or engraftment failure. This case indicates that dose-adjusted fludarabine, melphalan, and total body irradiation are sufficient and tolerable preparative regimens for allo-SCT in patients with hematologic malignant disease with ESRD requiring HD. All drugs used in treatment of the patient should be dialyzable or both metabolized and excreted by organs other than kidney because serum level of those drugs can be lowered with dialysis or spontaneously in the case of drug toxicity. Another considerable risk in posttransplant patients on HD is the high risk of infection. Because the immunity of HD patients is depressed, compared with normal individuals (8, 9), posttransplant infection risk for HD patients can be higher than that of patients with normal renal function. Because the risk of posttransplant complications may be high and treatment of these patients is extremely difficult, as described above, allo-SCT for those patients should be

Phase II Trial of Gemcitabine, UFT-E, Leucovorin Combination Chemotherapy in Advanced Pancreatic Adenocarcinoma.

PURPOSE To evaluate the efficacy and toxicity of a Gemcitabine, UFT-E, Leucovorin combination chemotherapy in the treatment of advanced pancreatic adenocarcinoma. PATIENTS AND METHODS Patients <=70 years, with no prior chemotherapy and with bidimensionally measurable advanced pancreatic adenocarcinoma, ECOG performance status <=2, and adequate bone marrow, kidney, and liver function were eligible for this trial. Eligibility criteria for clinical benefit assessment were pain with at least a daily analgesic consumption of two nonsteroidal anti-inflammatory drugs or a Karnofsky performance status between 50 and 70. Treatment consisted of 1,000 mg/m2 of Gemcitabine on days 1, 8 and 15, repeated every 4 weeks, with UFT-E administered orally 500 mg-700 mg by body surface area (BSA). Leucovorin was administered 45 mg/day orally. Dosages of UFT-E and Leucovorin were divided and administered three times per day from day 1 to day 21. After 7 days of rest, UFT-E and Leucovorin were administered repeatedly. RESULTS Twenty-three patients were enrolled between April 1999 to April 2000. Eighty two cycles (median, four cycles) were delivered to all patients. The objective response rate was 15.8% in 19 assessable patients and 13.0% in the intent-to-treat population. Twelve patients (57.9%) displayed stable disease. Grade 3 or 4 neutropenia occurred in 30.4% of patients, nausea/vomiting in 8.3%, diarrhea in 4.3%, and mucositis in 4.3%. The median time to progression was 8 months. The median survival was 8 months in the assessable population and 6 months in the intent-to-treat population Clinical benefit was achieved in 11 (57.9%) of 19 assessable patients. CONCLUSION Gemcitabine, UFT-E, Leucovorin combination chemotherapy is a well-tolerated and safe regimen in cases of advanced pancreatic adenocarcinoma. Although the response rate is low, it shows a survival benefit and clinical benefit and deserves further evaluation in a phase III trial.

A pilot study of daunorubicin-augmented hyper-CVAD induction chemotherapy for adults with acute lymphoblastic leukemia

Induction of complete remission (CR) is imperative for long-term survival in adult acute lymphoblastic leukemia (ALL) patients regardless of transplantation eligibility. Hyper-CVAD chemotherapy is a widely-used frontline remission induction regimen for these patients. We conducted a pilot trial of frontline remission induction using daunorubicin-augmented hyper-CVAD regimen (hyper-CVDD) in adult ALL patients (n = 15). The CR rate after this modified regimen was 100% (n = 15). Twelve patients were able to proceed to allogeneic hematopoietic cell transplantation, two patients died before transplantation due to infection, and the remaining one who was ineligible for transplant due to her age received an additional five courses of consolidation chemotherapy. Overall survival (OS) and event-free survival (EFS) of the study patients was 61.0 and 47.5% at 3 years. OS and relapse-free survival of transplanted patients was 66.8 and 55.0% at 3 years. This pilot trial demonstrates the favorable efficacy of the hyper-CVDD chemotherapy as a frontline remission induction regimen. Further clinical trials using this regimen are warranted.