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  • American Society of Hematology  (8)
  • 1
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 1512-1512
    Abstract: Abstract 1512 Introduction: The most comprehensive study on the prevalence and treatment of anemia in cancer patients in Europe (ECAS) dates from 2004. A reevaluation of treatment patterns for anemia in cancer patients (ACT, 2009) focused on patients treated with erythropoiesis-stimulating agents (ESAs). The study reported here aimed to assess current practice in the diagnosis and treatment of chemotherapy-induced anemia (CIA) as well as the role of iron therapy. Methods: Onco-hematologists in 5 European countries (France, Germany, UK, Spain, Switzerland; Jun - Oct 2009) completed forms asking for patient demographics, TNM stage of cancer, status of anemia, tests for diagnosis or confirmation of anemia, treatment, and if applicable details of iron therapy (used product, dosing regimen, reasons for prescription). Records of the last 5 CIA patients treated for anemia within the last 6 months were analyzed. Results are presented as mean [range] across countries. Results: 244 physicians (194 hospital-, 50 office-based) reported 1209 cases. Lymphoma (23%), myeloma (13%), lung (14%) and breast (12%) cancer were the most frequent cancer types. Metastatic disease was present in 66% of 662 patients with solid tumors. Tests to confirm anemia comprised mainly hemoglobin (Hb; 89% [85-95%]) and serum ferritin (48% [32-56%] ). Transferrin saturation (TSAT) was only tested in 13% [9-23%] of patients. In 11% of patients, Hb was the only test performed. At diagnosis, 71% [62-82%] presented with Hb ≤ 10 g/dL, the EMA/FDA recommended cut-off level for ESA treatment initiation. Ferritin ≤ 30 ng/mL, commonly used as an indicator of absolute iron deficiency, was seen in 17% [8-21%] of patients. However, 29% [18-80%] of patients tested for TSAT had levels ≤ 20%, indicating insufficient available iron for effective erythropoiesis. Anemia treatment included an ESA in 48% [13-81%] of patients. Although only 15% [9-22%] of patients had a Hb ≤ 8 g/dL at diagnosis, 54% [27-80%] received at least one blood transfusion in the 6 months prior to the survey. Iron treatment (oral or i.v.) was given in 23% [8-56%] of patients of whom, 62% received iron in combination with an ESA, 31% received iron in combination with red blood cell transfusion and 23% received iron alone; 35% in these three groups received i.v. iron. ‘Quick onset of action’ was stated as main reason for the use of i.v. iron in 35% of cases. Interestingly, the decision for oral iron treatment was justified by ‘Effective when used in combination’ in 31% of cases although clinical trials have shown that oral iron in contrast to i.v. iron does not add to the benefit of ESA therapy. Discussion: Despite pivotal trials showing the efficacy of i.v. iron supplementation in ESA-treated cancer patients and the potential to reduce required ESA doses or blood transfusions, the majority of anemic cancer patients are still treated with ESAs or blood transfusions alone. Only 23% receive iron therapy in routine practice. Compared to the patients who received anemia treatment in the 2004 ECAS study, this study reveals only moderately higher rates of iron treated patients (23 vs. 17%) whereas the frequency of blood transfusions is substantially higher (54 vs. 38%). Furthermore, only one third of iron treated patients receive i.v. iron despite of international guidelines recommending i.v. iron for the treatment of absolute and functional iron deficiency in cancer patients and oral iron has not been proven effective in these patients. This gap in the awareness about iron metabolism in specific patient populations is also reflected in the underuse of TSAT determination, a reliable and widely available marker of absolute and functional iron deficiency. Diagnosis of iron deficiency is still mainly based on ferritin although NCCN guidelines consider patients with ferritin levels up to 800 ng/mL as functionally iron deficient if TSAT is 〈 20%. This study confirms the need to increase awareness about the impact of cancer on iron metabolism and about evidence-based recommendations for i.v. iron supplementation. Disclosures: Beguin: Vifor Pharma: Honoraria, Membership on an Advisory Board. Aapro:Vifor Pharma: Honoraria, Membership on an Advisory Board. Bokemeyer:Vifor Pharma: Membership on an Advisory Board. Glaspy:Vifor Pharma: Membership on an Advisory Board. Hedenus:Vifor Pharma: Honoraria, Membership on an Advisory Board. Littlewood:Vifor Pharma: Honoraria, Membership on an Advisory Board. Ludwig:Vifor Pharma: Honoraria, Membership on an Advisory Board. Österborg:Vifor Pharma: Honoraria, Membership on an Advisory Board. Mitchell:Vifor Pharma: Employment.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 2
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 4715-4715
    Abstract: BACKGROUND. The A.C.T. study has shown that in Europe more cancer patients (pts) with anemia are being treated with ESAs than 7 years ago. ESAs are indicated in solid and hematological malignancies. Variability in treatment patterns, outcomes, and response rates in these tumor categories needs to be further explored. OBJECTIVE. To examine differences in anemia treatment patterns, outcomes, and response rates between patients with solid vs. hematological malignancies. DESIGN & PATIENTS. Multicenter, longitudinal retrospective study with 3 time points at approximately 1 month intervals; start of ESA treatment at visit 1. 307 centers in 13 European countries contributed 2192 pts (n=630 with hematological tumors; n=1562 with solid tumors) who were anemic (hemoglobin [Hb] 11g/dL) and treated with an ESA. MEASUREMENTS. Retrospective chart review. Variables reported here: age, chemotherapy regimen, Hb, WHO/ECOG performance status, ESA type, ESA dose incl. escalation, and iron supplementation. Response to ESA Rx: Hb rise≥1g/dl within 8 weeks, hematopoietic response (Hb rise≥2g/dl or Hb≥12g/dl achieved), Hb rise≥2g/dl, and Hb target range of 12.0–12.9g/dl achieved by visit 3. RESULTS. Pts ranged in age from 18 to 94 years (61.5 12.7) with no difference between groups (p=ns). 95.2% of pts were on chemotherapy, of which 92.9% on standard vs. 7.1% on high dose (solid 94.3% and 5.7% vs. hemato 89.1% and 10.9%, p=0.001); and 40.5% on platinum vs. 59.5% on nonplatinum (solid 49.1% and 50.9% vs. hemato 12.8% and 87.2%, p= & lt;0.001). Types of ESA included epoetin alfa (solid 23.2% vs. hemato 14.4%), epoetin beta (solid 41.7% vs. hemato 44.8%), darbepoetin alfa epoetin alfa (solid 34.6% vs. hemato 40.8%), and other epoetin alfa (solid 0.4% vs. hemato 0.0%; overall differences p & lt;0.001). Table 1. Visit 1 Visit 2 Visit 3 p p p Solid Hemato p Solid Hemato p Solid Hemato p (tumor type) (visit) (tumor type X visit) Mean (SD) ESA dose (IU/wk) 32601 (10037) 31067 (7247) & lt;0.001 33455 (11011) 32354 (9418) 0.034 33680 (11757) 32309 (9638) 0.027 0.023 & lt;0.001 n.s. Median ESAdose (IU/wk) 30000 30000 NA 30000 30000 NA 30000 30000 NA NA NA NA Mean (SD) Hb (g/dl) 9.6 (0.9) 9.3 (1.0) & lt;0.001 10.4 (1.2) 10.2 (1.5) 0.033 10.9 (1.4) 10.9 (1.7) n.s. 0.002 & lt;0.001 & lt;0.001 WHO/ECOG performance status 0.89 (0.73) 1.11 (0.87) & lt;0.001 0.77 (0.71) 0.92 (0.71) 0.002 0.76 (0.75) 0.88 (0.76) 0.013 & lt;0.001 & lt;0.001 0.004 % pts on iron 32.3% 16.5% & lt;0.001 22.6% 16.2% 0.006 22.4% 13.7% & lt;0.001 & lt;0.001 n.s. NA % pts on iron who are on IV iron 16.9% 24.5% n.s. 27.2% 34.5% n.s. 24.9% 32.7% n.s. n.s. n.s. NA % pts with & #x2028; ESA dose escalation 5.2% 6.5% n.s. 3.2% 2.5% n.s. n.s. n.s. NA Table 2. Hb ↑ ≥1g/dL Hb ↑ ≥1g/dL within 8 wks Hematopoietic response Hb ↑ ≥2g/dL Hb target 12–12.9g/dL Solid Hemato Solid Hemato Solid Hemato Solid Hemato Solid Hemato % of pts 63.0% 70.0% 53.4% 64.4% 35.5% 47.5% 29.8% 43.3% 17.9% 21.1% p 0.002 & lt;0.001 & lt;0.001 & lt;0.001 n.s. CONCLUSIONS. Slight increase in mean ESA dose between tumor types and across visits was not in accordance with the stable median ESA dose. Hb increased from visit 1 from visit 3 for all pts, but more so for pts with hematological malignancy, who moreover started out at lower Hb levels. Performance status increased in parallel with Hb, but more so for hematological patients. Hb levels were found to be an interaction of tumor type and time. A concomitant pattern was observed for performance status. Iron supplementation with esp. IV iron was consistently low, however with more hematological pts receiving esp. IV iron. Dose escalation rates were low, perhaps reflecting that this be an individualized patient decision. Response rates for pts with hematological malignancies were consistently higher than those for solid tumors, except for reaching Hb target of 12–12.9 g/dl. Hematological pts tended to have ESA Rx initiated at lower Hb levels thus showing more room for Hb improvement and therefore greater likelihood to fall in various responder categories. Overall, an increase of 1g/dl is achievable for the majority of pts. Adding time constraints, increasing the threshold level to ≥2g/dl, and/or setting an evidence-based target range of 12–12.9g/dl is associated with lower response rates in both groups, with slight advantage for hematological patients within caution above. ESAs are effective and safe in the management of cancer-related anemia for pts with hematological malignancies and solid tumors.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 3
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 1150-1150
    Abstract: EORTC/ASCO guidelines recommend primary prophylaxis (PP) with granulocyte colony stimulating factor (G-CSF) when the risk of chemotherapy (CT)-induced febrile neutropenia (FN) is ≥20%. Without G-CSF prophylaxis, FN risk in patients with non-Hodgkin’s lymphoma (NHL) receiving CHOP is up to 50%, and over 50% of FN occurs in cycle 1. Physicians often delay/reduce dose to manage neutropenia, potentially compromising CT efficacy. We identified 3 prospective clinical trials that assessed PP of neutropenia with pegfilgrastim (Neulasta®) 6 mg once per cycle in NHL patients receiving CHOP or CHOP-like regimens ± rituximab. In a retrospective integrated analysis, data from the 3 trials were combined to evaluate the efficacy and safety of PP with pegfilgrastim in a large NHL population. The primary outcome measure was the proportion of patients developing FN. In all, 280 patients started the first cycle of CT, of whom 275 (98%) received pegfilgrastim as PP and were included in the present analyses. The proportion of patients experiencing FN over all cycles was relatively low (15%), and approximately half of FN cases occurred during cycle 1 (Table). WHO grade 3/4 hematological toxicities occurred in the following proportions of patients: white blood cell count (WBC) & lt;2.0×109/L, 63%; absolute neutrophil count (ANC) & lt;1.0×109/L, 67%; hemoglobin & lt;8.0 g/dL, 8%; and platelets & lt;50×109/L, 21%. Grade 4 WBC & lt;1.0×109/L and ANC & lt;0.5×109/L were observed in 39% and 55% of patients. Fifteen percent of patients were hospitalized due to a neutropenic event and 11% were hospitalized due to FN. Anti-infectives were prescribed for 59% of patients. Across all CT cycles, relative dose intensity (RDI) ≥85% was achieved by 88% of patients and RDI ≥90% by 83% of patients. Pegfilgrastim was also effective as PP against FN in the subgroup aged ≥65 years (n=167), who are more susceptible to neutropenia. FN occurred in 17% of these patients (vs 12% of those aged & lt;65 years). Hospitalization due to neutropenic events and FN occurred in 19% and 14% of patients ≥65 years old compared with 9% and 6% of those aged & lt;65 years. To conclude, in this population, PP of FN with pegfilgrastim was associated with a relatively low occurrence of FN (15%) and a high proportion of patients achieving RDI ≥90%. These data support the use of pegfilgrastim 6 mg as PP against FN and neutropenic complications in NHL patients receiving CHOP-like CT, particularly the elderly for whom risk of FN and hospitalization is greatest. These findings support current ASCO/EORTC guideline recommendations. Patients starting each cycle, n (%) Patients with, n (%) [95% CI] FN RDI ≥90% *Data from one study only Cycle 1 275 (100) 20 (7) [4, 10] 250 (91) [88, 94] Cycle 2 259 (94) 7 (3) [1, 5] 225 (87) [83, 91] Cycle 3 244 (89) 7 (3) [1, 5] 202 (83) [78, 88] Cycle 4 221 (80) 8 (4) [1, 6] 174 (79) [73, 84] Cycle 5 173 (63) 2 (1) [0, 3] 132 (76) [70, 83] Cycle 6 158 (57) 5 (3) [0, 6] 132 (84) [78, 89] Cycle 7* 23 (13) 0 18 (78) [61, 95] Cycle 8* 19 (11) 0 15 (79) [61, 97] All cycles 275 (100) 41 (15) [11, 19] 228 (83) [78, 87]
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 4
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 4706-4706
    Abstract: BACKGROUND. The A.C.T. study has shown that in Europe more cancer patients (pts) with anemia are being treated with ESAs than 7 years ago. ESAs are indicated for lymphoma. Variability in treatment patterns, outcomes, and response rates in daily clinical practice need to be further investigated. OBJECTIVE. To examine anemia treatment patterns, outcomes, and response rates in the subsample of A.C.T. patients with lymphoma. DESIGN & PATIENTS. Multicenter, longitudinal retrospective study with at least 3 time points at approximately 1 month intervals, with visit 1 coinciding with start of ESA treatment. 128 centers in 13 European countries contributed 324 multiple myeloma pts who were anemic (hemoglobin [Hb] 11g/dL) and treated with an ESA (14.8% of total European sample). MEASUREMENTS. All data collected through retrospective chart review. Key variables reported here: age, chemotherapy regimen, Hb, WHO/ECOG performance status, ESA type, ESA dose incl. escalation, and iron supplementation. Response to ESA Rx: Hb rise ≥1g/dL, Hb rise ≥1g/dL within 8 weeks, hematopoietic response (Hb rise ≥2g/dL or Hb≥12g/dL achieved), Hb rise ≥2g/dL, and Hb target range of 12.0–12.9g/dL achieved by visit 3. RESULTS. Pts ranged in age from 18 to 92 years (58.4±17.6). 96.1% of pts were on chemotherapy, of which 83.4% on standard vs. 16.6% on high dose; and 17.8% on platinum vs. 82.2% on nonplatinum. Types of ESA prescribed included epoetin alfa (13.0%), epoetin beta (43.5%), darbepoetin alfa (43.5%). Results are summarized in Table 1. No severe adverse events were reported. Table 1 Treatment patterns and outcomes Visit 1 Visit 2 Visit 3 P Mean (SD) ESA dose (IU/week) 31851 (6912) 33844 (10296) 33610 (10199) 0.002 Median ESA dose (IU/week) 30000 30000 30000 n.s. Mean (SD) Hb (g/dL) 9.3 (1.0) 10.2 (1.4) 10.9 (1.7) & lt;0.001 WHO/ECOG performance status 1.04 (0.83) 0.98 (0.75) 0.90 (0.79) 0.002 % pts on iron 19.2% 18.1% 15.2% n.s. % pts on iron who are on IV iron 16.4% 23.3% 20.0% n.s. % pts with ESA dose escalation 8.4% 2.5% n.s. Response rates Hb↑≥1g/dL Hb↑≥1g/dL within 8wks Hematopoietic response Hb↑≥2g/dL 12–12.9g/dL % pts 67.9% 60.8% 44.4% 39.8% 20.7% CONCLUSIONS. The slight increase in ESA dose was not in accordance with the stable median ESA dose across the three visits. Hb increased from visit 1 from visit 3 with a concomitant rise in performance status. Iron supplementation with, in particular, IV iron was consistently low. Dose escalation rates were low, perhaps reflecting that this be an individualized patient decision. An increase in Hb of 1g/dL over the course of treatment is an attainable goal in two-thirds of lymphoma pts with anemia. Adding time constraints, increasing the threshold level to 2g/dL, and/or setting an evidence-based target range of 12–12.9g/dL is associated with lower response rates. In lymphoma pts, the therapeutic Hb goal to be achieved may need to be determined under consideration of multiple factors, however the general effectiveness of ESAs in this population is evident.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 5
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 4672-4672
    Abstract: BACKGROUND. The A.C.T. study has shown that in Europe more cancer patients (pts) with anemia are being treated with ESAs than 7 years ago. ESAs are indicated for hematological malignancies. Variability in treatment patterns, outcomes, and response rates in daily clinical practice need to be further investigated. OBJECTIVE. To examine anemia treatment patterns, outcomes, and response rates in the subsample of A.C.T. patients with hematological malignancies. DESIGN & PATIENTS. Multicenter, longitudinal retrospective study with at least 3 time points at approximately 1 month intervals, with visit 1 coinciding with start of ESA treatment. 152 centers in 13 European countries contributed 630 pts with hematological malignancies who were anemic (hemoglobin [Hb] ≤11g/dL) and treated with an ESA (14.8% of total European sample). MEASUREMENTS. All data collected through retrospective chart review. Key variables reported here: age, chemotherapy regimen, Hb, WHO/ECOG performance status, ESA type, ESA dose incl. escalation, and iron supplementation. Response to ESA Rx: Hb rise ≥1g/dL, Hb rise ≥1g/dL within 8 weeks, hematopoietic response (Hb rise ≥2g/dL or Hb ≥12g/dL achieved), Hb rise ≥2g/dL, and Hb target range of 12.0–12.9g/dL achieved by visit 3. RESULTS. Pts ranged in age from 18 to 92 years (62.4±15.3). 94.4% of pts were on chemotherapy, of which 89.1% on standard vs. 10.9% on high dose; and 12.8% on platinum vs. 87.2% on nonplatinum. Types of ESA prescribed included epoetin alfa (14.4%), epoetin beta (44.8%), darbepoetin alfa (40.8%). Results are summarized in Table 1.No severe adverse events were reported. Table 1 Treatment Patterns & Outcomes Visit 1 Visit 2 Visit 3 P Mean (SD) ESA dose (IU/wk) 31067 (7247) 32354 (9418) 32309 (9638) 0.001 Median ESA dose (IU/wk) 30000 30000 30000 n.s. Mean (SD) Hb (g/dL) 9.3 (1.0) 10.2 (1.5) 10.9 (1.7) & lt;0.001 WHO/ECOG performance status 1.11 (0.84) 0.92 (0.71) 0.88 (0.76) & lt;0.001 % pts on iron 16.5% 16.2% 13.7% n.s. % pts on iron who are on IV iron 24.5% 34.5% 32.7% n.s. % pts with ESA dose escalation 6.5% 2.5% 0.028 Response Rates Hb↑≥1g/dL Hb↑≥1g/dL within 8 wks Hematopoietic response Hb↑≥2g/dL Hb 12-12.9 g/dL 70% 64.4% 47.5% 43.3% 21.1% CONCLUSIONS. The slight increase in ESA dose was not in accordance with the stable median ESA dose across the three visits. Hb increased from visit 1 from visit 3 with a concomitant rise in performance status. Iron supplementation with, in particular, IV iron was consistently low. Dose escalation rates were low, perhaps reflecting that this be an individualized patient decision. An increase in Hb of 1g/dL over the course of treatment is an attainable goal in over two-thirds of pts with hematological malignancies who are anemic. Adding time constraints, increasing the threshold level to 2g/dL, and/or setting an evidence-based target range of 12–12.9g/dL is associated with lower response rates. In pts with hematological malignancies, the therapeutic Hb goal to be achieved may need to be determined under consideration of multiple factors, however the general effectiveness of ESAs in this population is evident.
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    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 6
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 2949-2949
    Abstract: Cyclophosphamide (CTX), a commonly used alkylating agent in the treatment of hematological malignancies and solid tumor diseases, is a prodrug metabolized to its active metabolite primarily via CYP2B6 with minor contribution of CYP3A4. CTX is also converted to neurotoxic and inactive metabolites mainly via CYP3A4. NEPA is a unique fixed-dose antiemetic combination of netupitant (NETU), a highly-selective NK1 receptor antagonist (RA) and palonosetron (PALO), a pharmacologically distinct 5-HT3 RA. Superiority of NEPA over PALO in preventing chemotherapy-induced nausea and vomiting was recently demonstrated in solid tumors. Although no significant drug-drug interactions between NETU, a moderate CYP3A4 inhibitor, and CTX are expected, NEPA has the potential to impact CTX metabolism and CTX-related toxicities. Methods This multinational, randomized, double-blind, parallel group study evaluated the efficacy and safety of a single oral dose of NEPA (NETU 300 mg + PALO 0.50 mg) versus a single oral 0.50 mg dose of PALO in chemotherapy-naïve patients receiving moderately emetogenic (anthracycline-CTX) chemotherapy for solid tumors during cycle 1 and during a multicycle extension, in the adjuvant, neoadjuvant or metastatic setting. All patients also received oral dexamethasone (DEX) on Day 1 (12 mg in the NEPA arm and 20 mg in the PALO arm). The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) in the delayed (25-120 hr) phase. Overall safety was assessed through reporting of adverse events. Results 1450 and 1286 patients were included in the safety population for cycle 1 and the multicycle extension, respectively; 76% of all patients completed cycle 4. Treatment groups were comparable with the overall population being female (98%) and white (80%), with a mean age of 54 years. The median CTX total dose in both groups was 1000 mg. Overall, the percentage of patients with at least one treatment-emergent adverse event (AE) was slightly higher for NEPA compared with PALO in cycle 1 but similar during the multicycle extension. The most commonly reported AEs were neutropenia, alopecia, and leukopenia, all known complications associated with CTX and anthracyclines. Frequencies of these AEs were comparable between treatment groups (36% vs 37%; 24% vs 23%; 22% vs 22%, respectively for NEPA vs PALO during the multicycle extension). All other AEs were reported by 〈 11% of patients and the type, frequency, and severity of AEs were comparable between groups throughout the study. The proportion of patients experiencing serious AEs or those leading to discontinuation was low and similar in both groups. Conclusion There was no indication in this large study of increased adverse events in patients receiving NEPA compared with those who received PALO after single or repeated cycles of CTX and anthracycline chemotherapy. As a convenient, fixed-dose dual-pathway antiemetic drug combination, NEPA has potential utility in hematologic malignancies and solid tumors. Disclosures: Schwartzberg: Helsinn Healthcare, SA: Consultancy, Honoraria; Eisai Inc: Consultancy, Honoraria. Rizzi:Helsinn Healthcare, SA: Employment. Rossi:Helsinn Healthcare, SA: Employment. Palmas:Helsinn Healthcare, SA: Employment. Karthaus:Helsinn Healthcare, SA: Consultancy. Aapro:Helsinn Healthcare, SA: Consultancy, Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 7
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 4716-4716
    Abstract: BACKGROUND. The A.C.T. study has shown that in Europe more cancer patients (pts) with anemia are being treated with ESAs than 7 years ago. ESAs are indicated for multiple myeloma. Variability in treatment patterns, outcomes, and response rates in daily clinical practice need to be further investigated. OBJECTIVE. To examine anemia treatment patterns, outcomes, and response rates in the subsample of A.C.T. patients with multiple myeloma. DESIGN & PATIENTS. Multicenter, longitudinal retrospective study with at least 3 time points at approximately 1 month intervals, with visit 1 coinciding with start of ESA treatment. 111 centers in 10 European countries contributed 306 multiple myeloma pts who were anemic (hemoglobin [Hb] ≤11g/dL) and treated with an ESA (14.0% of total European sample). MEASUREMENTS. All data collected through retrospective chart review. Key variables reported here: age, chemotherapy regimen, Hb, WHO/ECOG performance status, ESA type, ESA dose incl. escalation, and iron supplementation. Response to ESA Rx: Hb rise ≥1g/dL, Hb rise ≥1g/dL within 8 weeks, hematopoietic response (Hb rise ≥2g/dL or Hb≥12g/dL achieved), Hb rise ≥2g/dL, and Hb target range of 12.0–12.9g/dL achieved by visit 3. RESULTS. Pts ranged in age from 26 to 91 years (66.6 11.0). 92.5% of pts were on chemotherapy, of which 94.6% on standard vs. 5.4% on high dose; and 6.7% on platinum vs. 93.3% on nonplatinum. Types of ESA prescribed included epoetin alfa (16.0%), epoetin beta (46.1%), darbepoetin alfa (37.9%). Results are summarized in Table 1. No severe adverse events were reported. Table 1. Treatment patterns & outcomes Visit 1 Visit 2 Visit 3 p Mean (SD) ESA dose (IU/wk) 30237 (7509) 30676 (8012) 30760 (8698) n.s. Median ESA dose (IU/wk) 30000 30000 30000 n.s. Mean (SD) Hb (g/dl) 9.2 (1.0) 10.3 (1.5) 11.0 (1.7) & lt;0.001 WHO/ECOG (SD) performance status 1.17 (0.84) 0.87 (0.66) 0.86 (0.73) & lt;0.001 % pts on iron 13.7% 9.2% 7.8% n.s. % pts on iron who are on IV iron 36.6% 46.4% 45.8% n.s. % pts with ESA dose escalation 4.4% 2.5% n.s. Response Rates Hb↑≥ 1g/dl Hb↑≥1g/dl within 8wks Hematopoietic response Hb↑≥ 2g/dl 12– 12.9g/dl % pts 72.2% 68.5% 50.7% 47.1% 21.6% CONCLUSIONS. Mean and median dose did not change over time. Hb increased from visit 1 from visit 3 with a concomitant rise in performance status. Iron supplementation with, in particular, IV iron was consistently low. Dose escalation rates were low, perhaps reflecting that this be an individualized patient decision. An increase in Hb of ≥1g/dL over the course of treatment is an attainable goal in almost three-quarters of multiple myeloma pts with anemia. Adding time constraints, increasing the threshold level to ≥ 2g/dL, and/or setting an evidence-based target range of 12–12.9g/dL is associated with lower response rates. In multiple myeloma pts, the therapeutic Hb goal to be achieved may need to be determined under consideration of multiple factors, however the general effectiveness of ESAs in this population is evident.
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    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 8
    Online Resource
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    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 4821-4821
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4821-4821
    Abstract: Background: Cardiotoxicity is a well-known risk associated with anthracyclines, a widely prescribed class of chemotherapeutic agents. While the cumulative dose represents the greatest risk factor, concomitant use of other chemotherapy, such as cyclophosphamide can also contribute to this risk. As supportive care agents may be necessary to manage side effects associated with anthracycline treatment, it is critical that these agents do not contribute to the potential for cardiac adverse effects. NEPA is a unique fixed-dose antiemetic combination of netupitant (NETU), a new highly-selective NK1 receptor antagonist (RA) and palonosetron (PALO), an established pharmacologically distinct 5-HT3RA with a clean cardiac safety profile (Morganroth, ESMO 2007). Superiority of NEPA over oral PALO in preventing chemotherapy-induced nausea and vomiting associated with anthracycline-cyclophosphamide (AC) chemotherapy was recently demonstrated in a large multicycle study in solid tumors (Aapro, ASCO 2014). Because AC is also part of treatment utilized for hematologic malignancies, such as the CHOP combination, an evaluation of the cardiac safety of NEPA in this study is relevant to the hematology setting. Methods: This multinational, randomized, double-blind, parallel group study compared a single oral dose of NEPA (NETU 300 mg + PALO 0.50 mg) versus a single oral 0.50 mg dose of PALO in chemotherapy-naïve patients receiving AC chemotherapy for solid tumors during cycle 1 and during a multicycle extension. All patients also received oral dexamethasone on Day 1 (12 mg in the NEPA arm and 20 mg in the PALO arm). Cardiac safety was evaluated by cardiac adverse events, ECG changes, cardiac troponin levels (a biomarker used for early detection of cardiotoxicity) and left ventricular ejection fraction (LVEF, by ECHO). Results: 1450 and 1286 patients were included in the safety population for cycle 1 (n = 725 each group) and the multicycle extension (n = 635 NEPA, 651 PALO), respectively; 76% of all patients completed at least 4 cycles. Treatment groups were comparable with the majority of patients being female (98%) and white (80%), with a mean age of 54 years. The percentage of patients with at least one treatment-emergent adverse event (AE) classified as a cardiac disorder was similar for both groups in cycle 1 (2.6% NEPA vs. 2.1% PALO) and during the multicycle extension (5.0% vs. 4.6%). Overall, four AEs (n = 1 NEPA, n = 3 PALO) were classified as serious while none were considered related to study treatment. The percent of patients with treatment-emergent ECG abnormalities was comparable between groups. In cycle 1, the most frequently reported abnormalities were flat T waves (12.6% and 12.1% for NEPA and PALO, respectively). ST depression was the same in both groups (6.5%). The mean changes in QTcF were small and similar between groups and returned to baseline at 120 hours. The percentage of patients with increases from baseline of 〉 60 ms in QTcF were 0.7% and 1.1% for NEPA and PALO, respectively. This pattern for ECG abnormalities and QTcF changes was similar in the multicycle extension with no differences seen between groups. Similar proportions of patients had high troponin levels (ie, 〉 0.12 ng/mL) in cycle 1 (0.1% NEPA vs. 0.3% PALO) and in the multicycle extension (3.4% NEPA vs. 2.9% PALO). Of these, 0.4% NEPA and 0.7% PALO had troponin values greater than 0.50 ng/mL. In the majority of cases, the high values developed in cycles 5 and 6. Mean LVEF changes from screening to end of study were negligible and comparable between groups. Conclusions: In this large study of 1450 patients, there was no indication of increased cardiac safety concerns with the NEPA combination relative to PALO after single or repeated cycles of anthracycline-based chemotherapy. Consequently, clinicians can utilize this highly effective convenient, fixed-dose antiemetic drug combination with the knowledge that NEPA is not expected to contribute to the potential for cardiotoxicity seen with anthracyclines or other chemotherapies. Disclosures Karthaus: Helsinn Healthcare: Honoraria. Off Label Use: NEPA is a combination antiemetic currently under FDA review. Aapro:Helsinn Healthcare: Consultancy, Honoraria. Rizzi:Helsinn Healthcare: Employment. Palmas:Helsinn Healthcare: Employment.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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