Polypharmacy, Inappropriate Medication Use, and Drug Interactions in Older Korean Patients with Cancer Receiving First-Line Palliative Chemotherapy.

BACKGROUND: Polypharmacy is an important issue in the care of older patients with cancer, as it increases the risk of unfavorable outcomes. We estimated the prevalence of polypharmacy, potentially inappropriate medication (PIM) use, and drug-drug interactions (DDIs) in older patients with cancer in Korea and their associations with clinical outcomes. SUBJECTS, MATERIALS, AND METHODS: This was a secondary analysis of a prospective observational study of geriatric patients with cancer undergoing first-line palliative chemotherapy. Eligible patients were older adults (≥70 years) with histologically diagnosed solid cancer who were candidates for first-line palliative chemotherapy. All patients enrolled in this study received a geriatric assessment (GA) at baseline. We reviewed the daily medications taken by patients at the time of GA before starting chemotherapy. PIMs were assessed according to the 2015 Beers criteria, and DDIs were assessed by a clinical pharmacist using Lexi-comp Drug Interactions. We evaluated the association between polypharmacy and clinical outcomes including treatment-related toxicity, and hospitalization using logistic regression and Cox regression analyses. RESULTS: In total, 301 patients (median age 75 years; range, 70-93) were enrolled; the most common cancer types were colorectal cancer (28.9%) and lung cancer (24.6%). Mean number of daily medications was 4.7 (±3.1; range, 0-14). The prevalence of polypharmacy (≥5 medications) was 45.2% and that of excessive polypharmacy (≥10 medications) was 8.6%. PIM use was detected in 137 (45.5%) patients. Clinically significant DDIs were detected in 92 (30.6%) patients. Polypharmacy was significantly associated with hospitalization or emergency room (ER) visits (odds ratio: 1.73 [1.18-2.55], p < .01). Neither polypharmacy nor PIM use showed association with treatment-related toxicity. CONCLUSION: Polypharmacy, PIM use, and potential major DDIs were prevalent in Korean geriatric patients with cancer. Polypharmacy was associated with a higher risk of hospitalization or ER visits during the chemotherapy period. IMPLICATIONS FOR PRACTICE: This study, which included 301 older Korean patients with cancer, highlights the increased prevalence of polypharmacy in this population planning to receive palliative chemotherapy. The prevalence of polypharmacy and excessive polypharmacy was 45.2% and 8.6%, respectively. The prescription of potentially inappropriate medications (PIMs) was detected in 45.5% and clinically significant drug-drug interaction in 30.6% of patients. Given the association of polypharmacy with increased hospitalization or emergency room visits, this study points to the need for increased awareness and intervention to minimize polypharmacy in the geriatric cancer population undergoing chemotherapy. Moreover, specific criteria for establishing PIMs should be adopted for the treatment of older adults with cancer.

Interference with daily functioning by breakthrough pain in patients with cancer.

PURPOSE: To investigate the association between quality of life (QOL) and breakthrough cancer pain (BTCP) intensity in patients who met the commonly accepted definition of BTCP. METHODS: This study was a subset analysis of a South Korean multicenter, non-interventional, cross-sectional, nationwide survey. Participants were recruited from March 2016 to December 2017. BTCP was defined as a controlled background pain of less than a numeric rating scale (NRS) of 3 and any flare-up pain intensity. Pain intensity data were collected using the Brief Pain Inventory (BPI), which includes an interference assessment of the affective and physical domains. Patients were categorized by BTCP intensity into mild (NRS 1-3), moderate (4-6), and severe (7-10) groups. RESULTS: Of the 969 screened patients with cancer, 679 had ≤ NRS 3 background pain, of whom 438 completed the BPI. Of these 438 patients, 40, 204, and 194 were in the mild, moderate, and severe BTCP groups, respectively. The median NRS of BTCP was 6.0 (interquartile range = 5.0-8.0). Patients with moderate-severe BTCP had significantly higher interference with daily functioning (IDF) scores than did mild BTCP patients (3.3 vs. 5.7; p < 0.01). Both domains of IDF were significantly hampered proportionally by increased BTCP intensity (p < 0.001). The median total IDF scores of the no, moderate, and severe BTCP groups were 3.3, 5.0, and 6.9, respectively. Furthermore, IDF depended on BTCP intensity, duration, and frequency (p < 0.01) but not on pain type and cause. CONCLUSION: An increase in BTCP intensity is likely to result in IDF, regardless of the cause or type of BTCP.

A prospective, multicenter phase II study of continuous infusion of FLAG for patients older than 60 yr with resistant acute myeloid leukemia: a comparison with intensive younger patients' trial.

Relapsed or refractory acute myeloid leukemia (R/R AML) in elderly (≥60 yr old) patients were eligible. Induction chemotherapy consisted fludarabine and cytarabine (ARAC) as a 24-hr CI without idarubicin (C-FLAG), which was compared with the results of C-FLAG with idarubicin (CI-FLAG2) in younger patients' trial. A total of 33 and 68 patients were enrolled in C-FLAG and CI-FLAG2, respectively. CR, CRp, and CRi were achieved in 10 (30.3%), 3 (9.1%), and 2 (6.1%), respectively. When comparing outcomes between C-FLAG and CI-FLAG2, there were no difference in terms of CR rate (P = 0.572) and objective response rate (ORR; P = 0.899). Favorable predictors on ORR in C-FLAG were PB WBC ≤ 20K/uL at salvage (P = 0.024) and early evaluation peripheral BLAST = 0% (P = 0.013) on multivariate analysis. The overall survival of patients who achieve CR/CRp/CRi showed significantly prolonged survival compared with patients who did not in C-FLAG (P < 0.001) and was a favorable predictor of longer survival by multivariate analysis (P = 0.009). Median overall survival was 3.19 (95% CI, 2.05-4.33) months and similar with that of CI-FLAG2 (P = 0.841). Attenuated salvage regimen C-FLGA in elderly patients was as effective as more intensive younger patients' regimen CI-FLAG2 in terms of response and survival although elderly patients had more unfavorable clinical characteristics.

Comparable Allogeneic Hematopoietic Cell Transplantation Outcome of a Haplo-Identical Family Donor with an Alternative Donor in Adult Aplastic Anemia.

We performed a study on allogeneic hematopoietic cell transplantation (alloHCT) from an HLA-haplo-identical familial donor (haploFD) using a busulfan-fludarabine-antithymocyte globulin conditioning regimen for severe aplastic anemia (sAA) and hypoplastic myelodysplastic syndrome. For the comparison between a haploFD and an alternative donor (AD; matched unrelated or partially matched donor) for sAA in adults, we collected haploFD data retrospectively and prospectively. Forty-eight AD cases were selected for the comparison with 16 haploFD cases. All transplantation outcomes except for extensive chronic graft versus host disease (GvHD) were similar. The frequencies of hepatic sinusoidal obstruction syndrome (p = 1.000), acute GvHD (p = 0.769), grade 3/4 acute GvHD (p = 0.258), chronic GvHD (p = 0.173), extensive chronic GvHD (p = 0.099), primary neutrophil engraftment failure (p = 1.000), secondary graft failure (p = 1.000) and platelet engraftment failure (p = 0.505) were similar. Time to neutrophil engraftment was faster in haploFD (p = 0.003), while the cumulative incidence of platelet engraftment was similar (p = 0.505). Overall survival was also similar between AD and haploFD (p = 0.730). In conclusion, alloHCT from haploFD in sAA was comparable with alloHCT from AD, but extensive chronic GvHD seemed frequent in haploFD. Therefore alloHCT from haploFD could be an alternative approach for alloHCT from AD in adult sAA.

Efficacy and safety of deferasirox estimated by serum ferritin and labile plasma iron levels in patients with aplastic anemia, myelodysplastic syndrome, or acute myeloid leukemia with transfusional iron overload.

BACKGROUND: Patients receiving red blood cell (RBC) transfusions are at risk of iron overload, which can cause significant organ damage and is an important cause of morbidity and mortality. STUDY DESIGN AND METHODS: This study was an open-label, single-arm, prospective clinical study to evaluate the efficacy and safety of deferasirox (DFX) in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML). Patients with serum ferritin levels of at least 1000 ng/mL and ongoing transfusion requirements were enrolled. DFX was administered for up to 1 year. A total of 100 patients were enrolled. RESULTS: Serum ferritin levels decreased significantly following treatment (from 2000 to 1650 ng/mL, p = 0.004). The median absolute reduction in serum ferritin levels was -65 ng/mL in AA (p = 0.037), -647 ng/mL in lower-risk MDS (MDS-LR; p = 0.007), and -552 ng/mL in higher-risk MDS (MDS-HR)/AML (p = 0.482). Mean labile plasma iron (LPI) levels decreased from 0.24 µmol/L at baseline to 0.03 µmol/L at 1 year in all patients (p = 0.036). The mean LPI reduction in each group was -0.17 µmol/L in AA, -0.21 µmol/L in MDS-LR, and -0.30 µmol/L in MDS-HR/AML. Gastrointestinal disorders were commonly observed among groups (16.0%). DFX was temporarily skipped for adverse events in seven patients (7.0%) and was permanently discontinued in 11 patients (11.0%). CONCLUSION: DFX reduced serum ferritin and LPI levels in patients with transfusional iron overload. Despite the relatively high percentage of gastrointestinal side effects, DFX was tolerable in all subgroups.

Efficacy of Helicobacter pylori eradication for the 1st line treatment of immune thrombocytopenia patients with moderate thrombocytopenia.

The practical usefulness of Helicobacter pylori eradication for immune thrombocytopenia (ITP) patients is still controversial. However, some ITP patients respond to H. pylori eradication. We conducted a multi-center, open label, prospective phase II study to define the efficacy and toxicities of H. pylori eradication as the first line treatment for persistent or chronic ITP patients with moderate thrombocytopenia. Patients with persistent or chronic ITP showing moderate thrombocytopenia (30 × 10(9)/L ≤ platelet count ≤ 70 × 10(9)/L) and positive C(13)-urea breath test (UBT) were selected. Medication consisted of lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg orally twice daily for a week. Complete response (CR) rate at 4 weeks, 3 months, 6 months, 12 months, and maximal response was 19.2, 50.0, 50.0, 26.9, and 65.4%, respectively. Overall response rate (ORR) at 4 weeks, 3 months, 6 months, 12 months, and maximal response was 19.2, 57.7, 65.4, 30.8, and 69.2%, respectively. Median maximal platelet count during the first 3 months was 110 × 10(9)/L (range, 40-274). Median time to CR was 8 weeks (95% CI = 5.429-10.571). Median time to ORR was 4 weeks (95% CI = 1.228-6.772). Only per-protocol population was a response predictor for ORR at 3 months (70.0%, p = 0.054) and maximal ORR (80.0%, p = 0.051), but not for CR at 3 months (60.0%, p = 0.160). Therefore, eradication of H. pylori is an effective and durable first line treatment for persistent or chronic ITP with moderate thrombocytopenia with high ORR and rapid onset in this study.

Long-term follow-up of imatinib plus combination chemotherapy in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia.

The effects of imatinib plus chemotherapy were assessed in 87 patients with newly diagnosed Philadelphia chromosome-positive (Ph(+) ) acute lymphoblastic leukemia (ALL). Imatinib was administered continuously, starting from the eighth day of remission induction chemotherapy, then through five courses of consolidation or until allogeneic hematopoietic cell transplantation (HCT). Patients who were not transplanted were maintained on imatinib for 2 years. Eighty-two patients (94.3%) achieved complete remission (CR). Among these 82 CR patients, 40 experienced recurrence of leukemia. The 5-year relapse free survival (RFS) rate and overall survival (OS) rates were 39.0% and 33.4%, respectively. In total, 56 patients underwent allogeneic HCT in first CR. The 5-year cumulative incidence of relapse and OS rate of them were 59.1% and 52.6%, respectively. Six of seven patients who were maintained on imatinib after completion of consolidation relapsed and the median time of RFS was 40.7 months. In total patient, cumulative molecular CR rate was 88.5% and median time of molecular CR duration was 13 months. Initial imatinib dose intensity was significantly associated with median CR duration (P < 0.0001), and overall survival (P = 0.002). During the initial phase of treatment of patients with Ph(+) ALL, it is important to maintain imatinib dose intensity.

High-dose etoposide plus granulocyte colony-stimulating factor as an effective chemomobilization regimen for autologous stem cell transplantation in patients with non-Hodgkin Lymphoma previously treated with CHOP-based chemotherapy: a study from the Consortium for Improving Survival of Lymphoma.

We conducted a multicenter retrospective study to compare the efficacy and toxicity of various chemomobilization regimens: high-dose (HD) cyclophosphamide, HD etoposide (VP-16), and platinum-based chemotherapies. We reviewed the experiences of 10 institutions with 103 non-Hodgkin lymphoma patients who had previously only been treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. The mobilization yields for each regimen were analyzed. HD VP-16 mobilized a significantly higher median number of CD34(+) cells (16.22 × 10(6) cells/kg) than HD cyclophosphamide (4.44 × 10(6) cells/kg) or platinum-based chemotherapies (6.08 × 10(6) cells/kg, P < .001). The rate of successful mobilization (CD34(+) cell count ≥ 5.0 × 10(6) cells/kg) was also significantly higher for HD VP-16 (86%) than for HD cyclophosphamide (45%) or platinum-based chemotherapies (61%, P = .004). The successful mobilization rate on day 1 of 72% for HD VP-16 was significantly higher than the rates for HD cyclophosphamide (13%) and platinum-based chemotherapies (26%, P < .001). In multivariate analysis, HD VP-16 was a significant predictor of successful mobilization (P = .014; odds ratio, 5.25; 95% confidence interval, 1.40 to 19.63). Neutropenic fever occurred in 67% of patients treated with HD VP-16. The incidence was similar for HD cyclophosphamide (58%, P = .454) but was significantly lower for platinum-based chemotherapies (12%, P < .001). However, fatal (grade ≥ 4) infection and treatment-related mortality were not observed in this study. In conclusion, the mobilization yield was significantly influenced by the chemomobilization regimen, and HD VP-16 was a highly effective mobilization regimen in patients with non-Hodgkin lymphoma.

Lenalidomide with dexamethasone treatment for relapsed/refractory myeloma patients in Korea-experience from 110 patients.

We conducted a retrospective analysis of lenalidomide with dexamethasone for patients with relapsed/refractory multiple myeloma (RRMM) who were treated within the Korean patient access program. Lenalidomide has been approved for RRMM for several years in Europe and North America, but has not been accessible to Asian patients in the past. Between 2008 and 2012, 110 patients from 20 hospitals were enrolled. The overall response rate (ORR) was 43.6 % with 15.4 % of very good partial response (VGPR) or better. The median time to progression (TTP) in this heavily pretreated patient population was 8.0 months, and median overall survival (OS) was 23 months. Hematologic toxicities, fatigue, anorexia, and constipation were the most common adverse events. The number of previous treatment lines, previous exposure to thalidomide, refractoriness to thalidomide and bortezomib, pretreatment white blood cell count (WBC), platelet count, t(14;16), and 17p deletion were significant prognostic factors for TTP, and creatinine clearance, refractoriness to thalidomide and bortezomib, performance status, platelet count, and 17p deletion were significant for OS in univariate analysis. In multivariate analysis, WBC and platelet count were significant prognostic factors for TTP and performance status for OS. For Korean myeloma patients, lenalidomide showed considerable efficacy, and toxicities were comparable to the data published in Europe and North America.

The relationship between the success rate of empirical antifungal therapy with intravenous itraconazole and clinical parameters, including plasma levels of itraconazole, in immunocompromised patients receiving itraconazole oral solution as prophylaxis: a multicenter, prospective, open-label, observational study in Korea.

To identify the role of therapeutic drug monitoring of itraconazole (ITZ) in the setting of empirical antifungal therapy with intravenous (IV) ITZ, we performed a multicenter, prospective study in patients with hematological malignancies who had received antifungal prophylaxis with ITZ oral solution (OS). We evaluated the plasma levels of ITZ and hydroxy (OH) ITZ both before initiation of IV ITZ and on days 5-7 of IV ITZ. A total of 181 patients showed an overall success rate of 68.0 %. Prolonged baseline neutropenia and accompanying cardiovascular comorbidity were significantly associated with poor outcomes of the empirical antifungal therapy (P = 0.005 and P = 0.001, respectively). A significantly higher trough plasma level of OH ITZ per body weight was found in the patients who achieved success with empirical antifungal therapy (P = 0.036). There were no significant correlations between plasma concentrations of ITZ/OH ITZ (baseline or trough levels) and toxicities. Seven patients had a discontinuation of ITZ therapy due to toxicity. This study demonstrated that IV ITZ as empirical antifungal therapy was effective and therapeutic drug monitoring was helpful to estimate the outcome of empirical antifungal therapy in patients receiving antifungal prophylaxis with ITZ OS. To predict the outcome of empirical antifungal therapy with IV ITZ, we should evaluate baseline clinical characteristics and also perform the therapeutic drug monitoring of both ITZ and OH ITZ.

Prospective, multicenter, phase II study on reducing the dosage of idarubicin and FLAG for patients younger than 65 years with resistant acute myeloid leukemia: a comparison with a higher dosage trial.

We previously assessed continuous infusion (CI) of fludarabine and cytarabine plus idarubicin (CI-FLAG1) for patients under 65 years of age with resistant acute myeloid leukemia. Induction chemotherapy consisted of idarubicin (IDA) plus fludarabine and cytarabine (ARAC) as a 24-hour CI. In response to induction, 31.6% of patients achieved complete remission (CR) and in 68.4% the treatment failed. We concluded that CI-FLAG1 carried a high risk of toxicity and reduced CI-FLAG doses were recommended. Therefore, we revised the protocol (CI-FLAG2) by reducing the dose of IDA and ARAC. In total, 38 and 68 patients were enrolled into CI-FLAG1 and CI-FLAG2, respectively. When comparing outcomes between CI-FLAG1 and CI-FLAG2, there were no differences in terms of the CR rate (p = 0.306) and the overall response rate (ORR; p = 0.206). The treatment failure patterns were different between CI-FLAG1 and CI-FLAG2. The median overall survival showed only a trend towards longer survival in CI-FLAG2 (p = 0.074). Among intermediate-risk patients, there were high response rates favoring CI-FLAG2 in terms of the CR rate (p = 0.108), the ORR (p = 0.031), and overall survival (p = 0.033). This represented a relatively improved response rate compared to our previous study. There was decreased aplasia with dose reductions at the expense of increased resistance. A reduced dose of CI-FLAG might be most beneficial for intermediate-risk groups.

Success rate and risk factors for failure of empirical antifungal therapy with itraconazole in patients with hematological malignancies: a multicenter, prospective, open-label, observational study in Korea.

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462).

Efficacy of saam acupuncture treatment on improvement of immune cell numbers in cancer patients: a pilot study.

OBJECTIVE: To collect preliminary data on the effects of Saam acupuncture with regard to the immunity in cancer patients. METHODS: Ten cancer patients were analyzed for improvements in immunity. Acupuncture was applied at the 5 acupuncture points, Jingqu (LU 8), Zutonggu (BL 66), Yanggu (SI 5), Yangchi (TE 4), and Zhongwan (CV 12) for 2 weeks with 4 sessions. We assessed the effect of Korean Saam acupuncture on the immune system in cancer patients by measuring particular blood cell subsets, including CD3+, CD4+, CD8+, CD19+, and CD56+ cells, as well as total white blood cell count, absolute neutrophil count, and fatigue score. The measurement was performed before and after acupuncture and at a 2-week follow-up. RESULTS: There was a statistically significant increase in the number of CD3+ (P = 0.023) and CD8+ cells (P < 0.001) and T-cell subsets, as well as a decrease in the fatigue severity scale (FSS) score (P = 0.001) after Saam acupuncture using the 5 acupoints. CONCLUSION: Acupuncture may improve the immune system by increasing the counts of a few immune cells and relieve fatigue in cancer patients by decreasing FSS scores. Although this was a non-controlled study, it constitutes preliminary research investigating the potential effects of Saam acupuncture in increasing the counts of several immune cells in cancer patients.

A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia.

We conducted a phase 3 randomized trial comparing 2 different doses of daunorubicin as induction chemotherapy in young adults (60 years of age or younger) with acute myeloid leukemia (AML). Of 383 patients who were analyzed, 189 received standard-dose daunorubicin (SD-DN, 45 mg/m² per day times 3 days) and 194 received high-dose daunorubicin (HD-DN, 90 mg/m² per day times 3 days) in addition to cytarabine (200 mg/m² per day times 7 days) to induce complete remission (CR). The CR rates were 72.0% in the SD-DN arm and 82.5% in the HD-DN arm (P = .014). At a median follow-up of 52.6 months, overall (OS) and event-free (EFS) survival were higher in the HD-DN arm than in the SD-DN arm (OS, 46.8% vs 34.6%, P = .030; EFS, 40.8% vs 28.4%, P = .030). Differences in CR rate and both OS and EFS remained significant after adjusting for other variables (CR, hazard ratio [HR], 1.802, P = .024; OS, HR, 0.739, P = .032; EFS, HR, 0.774, P = .048). The survival benefits of HD-DN therapy were evident principally in patients with intermediate-risk cytogenetic features. The toxicity profiles were similar in the 2 arms. In conclusion, HD-DN improved both the CR rate and survival duration compared with SD-DN in young adults with AML. This study is registered at www.clinicaltrials.gov as #NCT00474006.

Escalated daunorubicin dosing as an induction treatment for Philadelphia-negative adult acute lymphoblastic leukemia.

The dose intensity of daunorubicin (DNR) delivered during the induction period represented the major prognostic factor for the outcome of adult acute lymphoblastic leukemia (ALL). The aim of this study was to determine the survival or toxicity of escalated doses of DNR in induction treatment of adult patients with acute lymphoblastic leukemia who are at least 15 years of age. For induction chemotherapy, all patients were given 90 mg/m(2)/day of DNR by continuous intravenous (IV) infusion over 24 h daily on days 1-3, 2 mg of vincristine IV push on days 1 and 8, and 60 mg/m(2)/day of prednisolone per oral (PO) on days 1-14 in conjunction with 4,000 units/m(2)/day of L-asparaginase intramuscular or subcutaneous on days 17-28. The median patient age was 32 years (range, 15-69). Complete remission (CR) was achieved in 169 (88.5 %) patients, while 4 died before CR was reached. Additionally, 11 patients died from leukemia progression, 4 had refractory disease, and 3 had follow-up loss. The median follow-up time was 697 days (range, 12-2,270). The 3-year cumulative incidence of relapse was 49.3 %. The probabilities of disease-free survival and overall survival at 3 years were 46.1 and 43.1 %, respectively. The dose of DNR was 100 % of the target dose, and there were no additional specific toxicities. The results show that escalated doses of DNR in induction chemotherapy are similar with the standard dose in response and toxicities. Our study indicates that a more effective regimen or better chemotherapy agents are needed to improve the CR rate and prolong survival in Philadelphia-negative adult ALL.

Noninterventional observational study using high-dose controlled-release oxycodone (CR oxycodone) for cancer pain management in outpatient clinics.

PURPOSE: Efficacy, safety, and quality of life (QoL) for patients receiving larger doses of controlled-release oxycodone (CR oxycodone) in outpatient clinics are evaluated. METHODS: The use of high-dose CR oxycodone and adjuvant drugs for pain management, pain intensity, parameters associated with quality of life, and adverse effects in cancer patients treated with high-dose CR oxycodone (≥80 mg/day) was prospectively observed for 8 weeks. Data from 486 cancer patients receiving high-dose CR oxycodone were collected from 44 hospitals during the period from February 2009 to March 2010. RESULTS: Three hundred eighteen of the total 486 patients treated with high-dose CR oxycodone were followed up for 8 weeks. Pain intensity significantly improved from a mean numeric rating scale (NRS) 5.49 to NRS 4.33 (P < 0.0001). Dosage of CR oxycodone increased from a mean of 130.0 to a mean of 174.9 (P < 0.0001). QoL including activity, walking, and sleeping significantly improved after 8 weeks. At baseline, 138 complained of adverse effects, of which constipation (30.2%) was the most common followed by dry mouth (8.8%) and dizziness (8.2%). After 8 weeks, 128 patients complained of adverse effects such as constipation (27.0%), nausea (5.7%), dry mouth (5.7%), and dizziness (5.0%). After 8 weeks of high-dose CR oxycodone, adverse effects did not increase. CONCLUSION: This study suggests that over an 8-week period, the use of high-dose CR oxycodone for cancer pain management is efficient, safe, and tolerable in outpatient clinics.

VEGFA and VEGFR2 genetic polymorphisms and survival in patients with diffuse large B cell lymphoma.

We evaluated the impact of functional polymorphisms in the vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor 2 (VEGFR2) genes on the survival of patients with diffuse large B cell lymphoma (DLBCL). Five potentially functional polymorphisms in the VEGFA (rs699947, rs2010963 and rs3025039) and VEGFR2 (rs1870377 and rs2305948) genes were assessed in 494 DLBCL patients treated with rituximab plus CHOP chemotherapy. The associations of genotype and haplotype with overall survival (OS) and progression-free survival (PFS) were analyzed. Of the five polymorphisms, VEGFR2 rs1870377T>A was significantly associated with both OS and PFS; in the dominant model, patients with the AA + TA genotypes had significantly better OS (P = 0.002) and PFS (P = 0.004) than those with the TT genotype. The association between significantly better OS and the AA + TA genotypes was observed separately in patients with low (0-2; P = 0.035) and high (3-5; P = 0.043) International Prognostic Index scores. Multivariate analysis showed that, relative to the AA + TA genotypes, the TT genotype was an independent prognostic factor for poor OS (HR, 1.71; 95% CI, 1.21-2.43; P = 0.002) and PFS (HR, 1.57; 1.13-2.17; P = 0.004). Other independent significant predictors of survival in patients with DLBCL were International Prognostic Index score, age > 60 years, lactate dehydrogenase concentration >normal, extranodal disease >1 and presence of B symptoms. The VEGFR2 rs1870377 polymorphism might affect survival in patients with DLBCL, suggesting that angiogenesis might be related to poor survival in these patients.

A phase II trial of erlotinib in combination with gemcitabine and capecitabine in previously untreated metastatic/recurrent pancreatic cancer: combined analysis with translational research.

BACKGROUND: To confirm the efficacy and toxicity of Erlotinib in combination with Gemcitabine and Capecitabine when used as a first-line therapy in metastatic/recurrent pancreatic cancer (PC). METHODS: Locally advanced PC was excluded. Erlotinib was given at a dose of 100 mg daily from D1 to D28. 1000 mg/m(2) of gemcitabine was given on D1,8,15 and 1660 mg/m(2)/day of capecitabine was given from D1 to 21, repeated every 4 weeks. Response was assessed every 8 weeks. RESULTS: A total of 47 patients were enrolled. Response rate and disease control rate was 32.6% (95% CI, 18.6-46.6%) and 83.7% (95% CI, 72.7-94.7%) respectively. The PFS was 6.5 months (95% CI, 3.4-9.7) and OS was 12.0 months (95% CI, 8.6-15.9). The Gr 3/4 toxicities were: neutropenia (6.8%), thrombocytopenia (3.2%), anemia (1.6%). nausea (1.6%), vomiting (1.6%), anorexia (5.3%), rash (2.4%). The EGFR expression was associated with shorter OS and ERCC2 expression was associated with longer PFS and OS. PFS and OS were not different according to K-RAS mutation or polymorphism of RRM1 and CDA. CONCLUSIONS: Erlotinib, gemcitabine and capecitabine combination showed promising efficacy and good tolerability in metastatic PC. This efficacy was observed irrespective of K-RAS mutation, and EGFR expression was poor prognostic factor for OS.

A randomized comparison of cyclophosphamide vs. reduced dose cyclophosphamide plus fludarabine for allogeneic hematopoietic cell transplantation in patients with aplastic anemia and hypoplastic myelodysplastic syndrome.

Recently, a less toxic regimen comprising reduced cyclophosphamide (Cy), fludarabine, and anti-thymocyte globulin (ATG) (Cy-Flu-ATG) was used to condition high-risk patients scheduled for allogeneic hematopoietic cell transplantation (alloHSCT) instead of standard Cy-ATG in patients with severe aplastic anemia (AA). We performed a randomized phase III study to compare the regimen-related toxicities (RRTs) of two different conditioning regimens: Cy-ATG vs. Cy-Flu-ATG. Patients in the Cy-ATG arm received Cy at 200 mg/kg. Those in the Cy-Flu-ATG arm received fludarabine (Flu) at 150 mg/m(2) and Cy at 100 mg/kg. A total of 83 patients (40 in the Cy-ATG and 43 in the Cy-Flu-ATG) were enrolled. Seventy-nine patients had AA and four had MDS. All predefined RRTs were significantly lower in patients of the Cy-Flu-ATG arm (23.3 vs. 55.0 %; p = 0.003). Infection with identified causative organism and sinusoidal obstruction syndrome, hematuria, febrile episodes, and death from any cause tended to be more frequent in Cy-ATG arm but did not differ significantly between arms. There was no difference in neutrophil engraftment failure (2.5 vs. 2.33 %; p = 0.959), acute graft-versus-host disease (GvHD) (15.0 vs. 23.3 %; p = 0.388), and chronic GvHD (16.7 vs. 16.2 %; p = 0.961) between Cy-ATG and Cy-Flu-ATG arms. The 4-year survival rate did not differ between the Cy-ATG and Cy-Flu-ATG arms. Preconditioning with Cy-Flu-ATG was superior to that afforded by Cy-ATG in terms of reducing RRT levels without increasing engraftment failure.

Comparable analysis of outcomes for allogeneic peripheral blood stem cell transplantation from matched related and matched unrelated donors in acute myeloid leukemia.

This study compared the results of allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated and related donors in 142 consecutive patients with acute myeloid leukemia (AML). The cumulative incidence of acute graft-versus-host disease (GVHD) was 37.6% in the related PBSCT group and 53.7% in the unrelated PBSCT group. The cumulative incidence of extensive chronic GVHD was also higher in the unrelated PBSCT group (19.5%) than in the related PBSCT group (8.9%). The overall survival rate at 4 years was 62.4 ± 5.4 and 53.8 ± 1.2% (p = 0.535) in the related and unrelated PBSCT group, respectively. In a multivariate analysis, unrelated PBSCT was identified as a risk factor for the development of extensive chronic GVHD (hazard ratio = 3.019, p = 0.027). Unfavorable cytogenetics and the disease status at the time of transplantation were found to be related to overall survival. In the case of high-risk AML, the survival rate and relapse incidence were significantly better in the matched unrelated PBSCT group (p = 0.047 and 0.039, respectively). In conclusion, the allogeneic PBSCT outcomes for AML were comparable in the matched related and matched unrelated groups. Nonetheless, for high-risk AML patients, matched unrelated PBSCT was found to be preferable to matched related PBSCT.