Comparison of the Management of Anemia in Patients with Solid Versus Hematological Malignancies Treated with Erythropoiesis Stimulating Agents (ESAs): Findings from the European Anemia Cancer Treatment (A.C.T.) Study

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=<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<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) <0.001 33455 (11011) 32354 (9418) 0.034 33680 (11757) 32309 (9638) 0.027 0.023 <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) <0.001 10.4 (1.2) 10.2 (1.5) 0.033 10.9 (1.4) 10.9 (1.7) n.s. 0.002 <0.001 <0.001 WHO/ECOG performance status 0.89 (0.73) 1.11 (0.87) <0.001 0.77 (0.71) 0.92 (0.71) 0.002 0.76 (0.75) 0.88 (0.76) 0.013 <0.001 <0.001 0.004 % pts on iron 32.3% 16.5% <0.001 22.6% 16.2% 0.006 22.4% 13.7% <0.001 <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   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 <0.001 <0.001 <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.

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Management of Anemia in Patients with Hematological Malignancies Treated with Erythropoiesis Stimulating Agents (ESAs): Findings from the European Anemia Cancer Treatment (A.C.T.) Study

Blood ◽

10.1182/blood.v112.11.4672.4672 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4672-4672

Author(s):

Heinz Ludwig ◽

Pierre Soubeyran ◽

Matti Aapro ◽

Carsten Bokemeyer ◽

Michael Muenzberg ◽

...

Keyword(s):

Dose Escalation ◽

Iron Supplementation ◽

Hematological Malignancies ◽

Performance Status ◽

Response Rates ◽

Treatment Patterns ◽

Target Range ◽

Ecog Performance Status ◽

Iv Iron ◽

Hematopoietic Response

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) <0.001 WHO/ECOG performance status 1.11 (0.84) 0.92 (0.71) 0.88 (0.76) <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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Management of Anemia in Lymphoma Patients Treated with Erythropoiesis Stimulating Agents (ESAs): Findings from the European Anemia Cancer Treatment (A.C.T.) Study

Blood ◽

10.1182/blood.v112.11.4706.4706 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4706-4706

Author(s):

Heinz Ludwig ◽

Carsten Bokemeyer ◽

Pierre Soubeyran ◽

Matti Aapro ◽

Michael Muenzberg ◽

...

Keyword(s):

Dose Escalation ◽

Iron Supplementation ◽

Performance Status ◽

Response Rates ◽

Treatment Patterns ◽

Target Range ◽

High Dose ◽

Ecog Performance Status ◽

Iv Iron ◽

Hematopoietic Response

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) <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.

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Management of Anemia in Multiple Myeloma Patients Treated with Erythropoiesis Stimulating Agents (ESAs): Findings from the European Anemia Cancer Treatment (A.C.T.) Study

Blood ◽

10.1182/blood.v112.11.4716.4716 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4716-4716

Author(s):

Heinz Ludwig ◽

Matti Aapro ◽

Carsten Bokemeyer ◽

Pierre Soubeyran ◽

Michael Muenzberg ◽

...

Keyword(s):

Multiple Myeloma ◽

Dose Escalation ◽

Iron Supplementation ◽

Performance Status ◽

Response Rates ◽

Treatment Patterns ◽

Target Range ◽

High Dose ◽

Iv Iron ◽

Hematopoietic Response

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) <0.001 WHO/ECOG (SD) performance status 1.17 (0.84) 0.87 (0.66) 0.86 (0.73) <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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Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (I-O) drugs.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.2506 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 2506-2506

Author(s):

Anthony W. Tolcher ◽

James Andrew Reeves ◽

Meredith McKean ◽

Bartosz Chmielowski ◽

Joseph Thaddeus Beck ◽

...

Keyword(s):

Metastatic Melanoma ◽

Solid Tumors ◽

Phase Ii ◽

Phase Ii Study ◽

Performance Status ◽

Nerve Sheath Tumor ◽

Advanced Solid Tumors ◽

Antitumor Effects ◽

Ecog Performance Status ◽

Multiple Tumor

2506 Background: Alrizomadlin (APG-115) restores TP53 function, activating p53-mediated apoptosis in tumor cells with wild-type TP53 and/or MDM2 amplification. Alrizomadlin also functions as a host immunomodulator and hence may restore antitumor activity in pts with cancers failing PD-1/PD-L1 blockade. Methods: This US multicenter trial assessed alrizomadlin combined with pembrolizumab in pts with unresectable/metastatic melanoma or advanced solid tumors that had failed I-O drugs; or pts with malignant peripheral nerve sheath tumor (MPNST), liposarcoma, or ATM mutant solid tumors that had failed any standard therapy. Eligible pts had ECOG performance status of 0-2 and no CNS metastases. The phase II study cohorts included pts with melanoma, NSCLC, solid tumor with ATM mutation, well-differentiated/dedifferentiated liposarcoma, urothelial carcinoma, and MPNST. Alrizomadlin was administered orally at 150 mg once every other day for 2 consecutive weeks with 1 week off and pembrolizumab at 200 mg via IV infusion for 30 minutes on Day 1 of a 21-day cycle. Results: As of December 25, 2020, 84 pts had been treated in 6 cohorts: melanoma (n = 26), NSCLC (n = 23), ATM mutation (n = 9), liposarcoma (n = 14), urothelial (n = 9), and MPNST (n = 3). In the PD-1/PD-L1 inhibitor-failed melanoma cohort, there was 1 confirmed partial response (PR) out of 5 pts with uveal melanoma, 2 PR (1 confirmed and 1 unconfirmed) of 5 pts with mucosal melanoma, and 1 confirmed PR of 11 pts with cutaneous melanoma. ORR in the melanoma cohort was 17.4% (4/23 evaluable pts), and the disease control rate was 60.9% (14/23). In the MPNST cohort, 1 of 3 pts had an unconfirmed ongoing PR. In I-O drug-failed NSCLC (n = 14 evaluable) and urothelial (n = 5 evaluable) cohorts, each reported 1 confirmed PR. Common treatment (alrizomadlin or pembrolizumab)-related adverse events (TRAEs) (≥ 10%) were nausea (63.1%), thrombocytopenia (36.9%), vomiting (33.3%), fatigue (31.0%), decreased appetite (27.4%), diarrhea (21.4%), neutropenia (15.4%), and anemia (11.9%). Grade ≥ 3 TRAEs (≥ 5%) included thrombocytopenia (20.2%), neutropenia (14.2%), and anemia (8.3%). Eleven pts discontinued treatment due to AEs: 5 were treatment related, including 2 grade 4 thrombocytopenia, and 1 each of grade 2 vomiting, grade 2 fatigue, and grade 2 posterior reversible encephalopathy syndrome (PRES). Three treatment-related SAEs were PRES, pyrexia, and asthenia. Conclusions: Alrizomadlin combined with pembrolizumab is well tolerated and may restore antitumor effects in pts with cancer resistant to or intolerant of I-O drugs, as suggested by preliminary antitumor activities in multiple tumor types. Internal study identifiers: APG-115-US-002; Keynote MK-3475-B66. Clinical trial information: NCT03611868.

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Safe use of Peripherally Inserted Central Catheters for chemotherapy of solid malignancies in adult patients: A 1-year monocentric, prospectively-assessed, unselected cohort of 482 patients

The Journal of Vascular Access ◽

10.1177/1129729820962905 ◽

2020 ◽

pp. 112972982096290

Author(s):

Alessio Piredda ◽

Davide Radice ◽

Claudia Zencovich ◽

Martina Cerri ◽

Lucia Aventino ◽

...

Keyword(s):

Hematological Malignancies ◽

Blood Stream Infection ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Adult Patients ◽

Time Interval ◽

Ecog Performance Status ◽

Peripherally Inserted Central Catheters ◽

Central Catheters ◽

Unselected Cohort

Introduction: Aim of this study was to analyze the overall complication and failure rates of Peripherally Inserted Central Catheters (PICCs), in a 1-year consecutive unselected cohort of 482 adult patients, affected by non-hematological malignancies undergoing chemotherapy. Methods: Adult outpatients (aged 18–75 years), with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, bearing solid tumors and candidates for intravenous chemotherapy were eligible for the study. Exclusion criteria were active infections, coagulopathy (defined as platelet count <50,000/μL and/or prothrombin time more than 18 s), life expectancy <6 months, or inability to give written informed consent. Devices were all implanted in an outpatients’ hospital facility, following predefined evidence-based institutional guidelines and protocols by a PICC-dedicated team at the European Institute of Oncology in Milan, Italy, during the 12-month period from January 1 to December 31, 2019. Results: Five-hundred PICCs were implanted in a cohort of 482 patients during the time interval of this study. Thirty devices were overall removed (6.2%), 23 as a consequence of a complication occurred, and seven inadvertently. The inserted PICCs accounted for a total of 49,718 catheter days in situ, median duration was 85.5 days [interquartile range (IQR): 56–146]. Overall there were 42 (8.7%) complications, corresponding to 0.84 catheter-adverse events (CAE)/1000 PICC-days (95% CI: 0.61–1.14). There were N = 13 (2.7%) thromboses, N = 11 (2.3%) irreversible occlusions, N = 7 (1.5%) accidental removals, N = 5 (1.0%) infections [two Catheter Related Blood Stream Infection (CRBSI) and three exit site/local infection], N = 3 (0.6%) ruptures and N = 3 (0.6%) primary or secondary malpositions. Conclusion: This large prospective study supports the increasing use of PICCs in adult oncology outpatients treated in specialized centers with chemotherapy for non-hematological malignancies. In this clinical setting, PICC failure occurred in 6% only of the inserted devices.

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R-CHOP in the Treatment of DLBCL: Single Institution Experience from North India.

Blood ◽

10.1182/blood.v106.11.4773.4773 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4773-4773

Author(s):

Ashok K. Vaid ◽

Sachin Gupta ◽

Dinesh C. Doval ◽

Vineet Talwar ◽

Rajeev Gupta ◽

...

Keyword(s):

Performance Status ◽

B Cell Lymphoma ◽

Response Rates ◽

North India ◽

Base Line ◽

Extranodal Involvement ◽

Ecog Performance Status ◽

Chop Regimen ◽

Bulky Disease ◽

2D Echocardiography

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of NHL. Different chemotherapy regimens tested in the past showed RR of appx 80% with no improvement in prognosis & OS. CHOP regimen has been the standard treatment for these patients (pts). Rituximab has improved response rates & survival in CD20 positive lymphoma pts, especially elderly (GELA trial: CR 73% vs. 63%). We retrospectively evaluated pts of DLBCL treated with R-CHOP regimen between April 2001 & June 2005. All pts had biopsy and IHC of lymph node/extranodal site, & CT scan of neck, chest, abdomen; BM biopsies; CBC, serum chemistries; 2D echocardiography/MUGA scans. All pts received Rituximab (375mg/m2) & CHOP 3 weekly for a maximum of 8 cycles. Pts who received at least 1 & 3 cycles of R-CHOP were evaluable for toxicity and response respectively. In total, 36 pts were included for analysis. The median age was 53 years, 10/36 pts (27.8%) were >60 years. 25/36 were male (69.4%). ECOG performance status: 0–1 in 30/36, and 2–4 in 6/36. 11/36 had B-symptoms, 16/36 had high LDH, 6/36 had bulky disease. Extranodal involvement was present in 19/36; 10/36 had ≥2 sites of extranodal involvement. Lymph nodal swelling was most common presentation in 24/36 (66.7%), followed by pain 10/36 (27.8%), weight loss 9/36 (25%), fever 7/36 (19.4%), skin nodules 3/36 (8.3%). Extranodal sites were: bone marrow 5/36, bone 4/36, skin 3/36, GIT 3/36, pleural effusion 2/36, lungs 2/36, other soft tissue 2/36, and parotid, nasopharynx, orbit, adrenal, testes, kidneys-1 each. Gallium scan at base line, done in 12/36, was positive in 11 pts (91%). Stage distribution was as follows: stage-I none, stage-II 10/36 (27.8%), stage-III 13/36 (36.1%), stage-IV 13/36 (36.1%). IPI scoring was-low risk 13/36 (36.1), low intermediate 9/36 (25.0%), high intermediate 13/36 (36.1) & high risk 1/36 (2.8%). A total of 199 cycles of R-CHOP were administered with a median of 6 cycles per patient. Of the 33 pts evaluable for response, 22 achieved CR (66.7%), 9 PR (27.3%), 1 each SD & PD. There were 2 treatment related mortalities. Toxicities were: grade III/IV neutropenia in 12/36 (33.3%), thrombocytopenia 4/36 (11.1%), peripheral neuropathy 2/36 (5.6%). Mild hypersensitivity to Rituximab was seen in 2/36 (5.6%) pts. Only 1 patient had cardiac toxicity in form of CHF. Our study showed response rates (94%) and toxicity profile similar to what has been reported in other studies with R-CHOP. The follow-up is too short to evaluate survival rates. Keywords: DLBCL, Rituximab, CHOP.

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Final results of a prospective, observational study of the effectiveness of darbepoetin alfa administered every three weeks for the treatment of chemotherapy-induced anaemia in elderly patients

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e20654 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e20654-e20654

Author(s):

G. Esquerdo ◽

M. Doménech ◽

J. C. Bermejo ◽

P. López ◽

C. Pedro ◽

...

Keyword(s):

Darbepoetin Alfa ◽

Performance Status ◽

Specific Treatment ◽

Red Blood Cell Transfusion ◽

Fixed Dose ◽

Ecog Performance Status ◽

Myeloid Malignancies ◽

Treatment Data ◽

Practice Methods ◽

Hematopoietic Response

e20654 Background: Cancer incidence is increasing in elderly but specific treatment data in this population is not often available. The objectives of this study were to evaluate the effectiveness and safety of darbepoetin alfa (DA) administered once every 3 weeks (Q3W) for the treatment of chemotherapy-induced anaemia (CIA) in elderly within routine clinical practice. Methods: Prospective, observational, single-arm, multicentre study performed in 28 centres across Spain. Eligible patients (pts):≥65 years, anaemic (haemoglobin [Hb] 11 g/dl), with non-myeloid malignancies, and scheduled to receive ≥9 weeks (wks) of chemotherapy. Pts were treated with a fixed dose of DA 500 μg Q3W and treatment stopped if Hb levels exceeded 13g/dl. Primary endpoint was hematopoietic response (Hb increase ≥2g/dl or Hb ≥12g/dl without transfusions in the previous 28 days). Secondary endpoints included percentage of pts achieving target Hb (>11g/dl from wk 5 till end of treatment without red blood cell transfusion within 28 days), changes in the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) scale and the incidence of adverse reactions. Results: Data were prospectively collected from 153 pts: women (56.86%), mean (SD) age 73.43 (5.77) years, ECOG Performance Status 0–1 (65.36%) with solid tumors (66.67%) and lymphoproliferative malignancies (33.33%) and stage III/IV (63.40%). Most pts (90.20%) had baseline Hb levels between 9–11g/dL. DA was administered for a median of 9.0 wks (range: 1–22.57). The Kaplan-Meier percentage (KM; 95% CI) of pts who achieved hematopoietic response was 69.70% (56.06–83.34) and 72.22% (57.5–86.94) for pts who achieved target Hb (>11g/dL). FACT-F median score at baseline was 29.00 and 33.00 at the end of the study. Only one (0.7%) non-serious adverse reaction (cutaneous eruption) was reported. Conclusions: These results suggest that DA given at 500 μg Q3W to elderly pts with non-myeloid malignancies is an effective and well-tolerated treatment for CIA. [Table: see text]

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A phase I trial of bexarotene and docetaxel in patients with advanced solid tumors

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.13085 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 13085-13085

Author(s):

M. J. Pishvaian ◽

K. Firozvi ◽

J. J. Hwang ◽

J. L. Marshall ◽

P. Ramzi ◽

...

Keyword(s):

Phase I ◽

Solid Tumors ◽

Phase I Trial ◽

Performance Status ◽

Fixed Dose ◽

Ecog Performance Status ◽

Radiation Recall ◽

Serum Triglycerides ◽

Experienced Grade ◽

Grade Iii

13085 Background: Retinoids have been used to treat a wide variety of malignancies. Bexarotene is a synthetic retinoid that binds preferentially to the RXR subclass of retinoid receptors. In the initial phase I trial of bexarotene, a subset of patients with non-small cell lung cancer (NSCLC) had prolonged stabilization of disease and survival. In vitro evidence suggests that the effects of retinoids may be enhanced when used in conjunction with taxanes. This is a phase I trial designed to determine the maximum tolerated dose of docetaxel in combination with a fixed dose of bexarotene. Methods: Patients with pathologically confirmed solid tumors for whom no standard therapies exist, who have an ECOG performance status ≤2, adequate organ function and normal serum triglycerides were eligible. Each cycle was 4 weeks long. Oral bexarotene was given at 400 mg/m2 daily. Docetaxel was given weekly for 3 out of 4 weeks at two dose levels, 25 or 30 mg/m2, for up to 6 cycles. For patients exhibiting disease stabilization or response, treatment with bexarotene was continued until disease progression. Restaging studies were performed after every 2 cycles. Results: To date 10 patients have been enrolled, half of whom had NSCLC - 7 male, mean age = 61 (range 37–73), 100% PS = 0 or 1. 29 cycles were completed (range 1 to 8). 7 patients have been treated at 25 mg/m2 and 3 at 30 mg/m2 of docetaxel. Hypothyroidism, hypertriglyceridemia, and fatigue were common but generally mild. Two patients experienced grade III fatigue, and 1 each experienced grade III hypertriglyceridemia, neutropenia, and cough. There were no grade IV toxicities. Two patients were taken off study because of non-fatal radiation recall pneumonitis that was controlled with steroids. In this heavily pretreated population, of 8 patients assessable for response, 5 had stable disease for at least 2 cycles. One patient with NSCLC had a partial response that persisted for 6 cycles. Conclusions: Bexarotene and docetaxel (at a minimum of 25 mg/m2) can be safely coadministered. Care should be taken in patients who have been previously irradiated. Enrolment and dose escalation for the phase I trial is still ongoing. A phase II trial of the combination as second line therapy in NSCLC is planned. [Table: see text]

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Phase I study of the novel pro-drug MIV-818 in patients with hepatocellular carcinoma, intra-hepatic cholangiocarcinoma or liver metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.309 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 309-309

Author(s):

T.R. Jeffry Evans ◽

Eric Van Cutsem ◽

Hans Prenen ◽

Mark R. Middleton ◽

Debashis Sarker ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Dna Damage ◽

Liver Metastases ◽

Solid Tumors ◽

Dose Escalation ◽

Performance Status ◽

Ecog Performance Status ◽

Phase Ib ◽

Starting Dose ◽

Liver Biopsies

309 Background: MIV-818 is an orally administered troxacitabine (TRX)-based nucleotide prodrug. It is highly metabolized by human hepatocytes, directing high levels of the chain-terminating nucleotide tri-phosphate to the liver, while minimizing exposure to other organs. The tri-phosphate is incorporated into DNA during replication, which leads to DNA double strand breaks, DNA damage responses, and cytotoxicity. Methods: Patients (pts), ≥18 years, ECOG performance status < 1, adequate organ function, with treatment-refractory hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA) or liver metastases (LM) from solid tumors were enrolled. In phase Ia, MIV-818 monotherapy was administered in an intra-patient dose-escalation design with doses of 3-70mg for 3-5 days in cycles of 21 days. Phase Ib is an inter-patient dose escalation in a 3+3 cohort design and is currently ongoing. Treatment is given until disease progression or unacceptable toxicity. The primary objective is to assess safety and tolerability and, for phase Ia, also to establish the starting dose for phase Ib. Key secondary objective was to evaluate the overall response rate based on RECIST v1.1. The pharmacokinetics of MIV-818 and its metabolites were evaluated, and on-treatment liver biopsies were collected to assess the pharmacokinetics and the pharmacodynamic effects of MIV-818. Results: Nine patients (7M; 2F), ECOG performance status 0 (n=3) or 1 (n=6), median age = 57 years (range: 50-84) with HCC (2 pts), iCCA (1) or LM (6) from solid tumors (mainly GI tract), previously treated with median 2 (1-5) lines of therapy, were included in phase Ia. Patients were dosed up to 60 mg 5 days/week. The most common treatment related AEs were those in the hematological system: neutropenia grade (gr) 1-4, neutropenic sepsis gr 4; thrombocytopenia gr 1-2, anemia gr 1-2. Elevated bilirubin gr 1-3 and liver enzymes gr 3 were also reported. Most of the AEs were reversible. Five pts discontinued due to AE and 4 pts discontinued due to progressive disease outside the liver after 2-4 cycles. Starting dose of phase Ib was determined to be 40mg 5 days/week. Tumor biopsies showed evidence of selective DNA damage in tumor tissue, including in hypoxic regions, with minimal or no impact of MIV-818 observed in healthy liver tissue. Conclusions: MIV-818 had an acceptable safety and tolerability profile. Biomarker data of liver biopsies demonstrated a selective effect of MIV-818 on cancer cells. Updated safety and efficacy data from phase Ib will be presented at the meeting. (NCT03781934). Clinical trial information: 2018-000995-14.

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Impact of the G8 score on the outcome of a cohort of elderly patients with solid or hematological malignancies.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.12038 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 12038-12038

Author(s):

Federica Biello ◽

Alessia Mennitto ◽

Abdurraouf Mahmoud ◽

Francesca Platini ◽

Daniela Ferrante ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Elderly Patients ◽

Solid Tumors ◽

Hematological Malignancies ◽

Screening Tool ◽

Tumor Type ◽

Risk Of Death ◽

Increased Risk ◽

G8 Screening Tool

12038 Background: Elderly cancer patients may have important benefits from innovative treatments. However, they are often barred from clinical trials because of highly selective eligibility criteria, or due to biased and subjective physician standpoints including reluctance to invite elderly patients and fear of excessive toxicity. Indeed, geriatric assessment has been increasingly recognized as predictive and prognostic instrument to detect frailty in older adults with cancer. In this perspective, the G8 score is a simple and reproducible instrument to identify elderly patients who should undergo full geriatric evaluation. The aim of our study was to evaluate the impact of frailty assessment by the G8 screening tool on the outcome of onco-hematological patients. Methods: Between January 2017 and December 2020 the G8 screening tool was administered to patients, aged >65 years, referred to our center for solid and hematological malignancies. G8 score was assessed at the time of first access. The primary endpoint was overall survival. Multivariate analysis was performed according to G8 score, age, tumor type, stage and treatment. Results: In the observation period, 430 patients were screened for frailty by G8; median age was 77 years (65-92); of these, 331 (77%) had a G8 score <14. Pts with solid tumors were 310 (72%), 175 (57%) of whom had metastatic diseases; 227 (73%) had a G8 score <14. Pts with hematological malignancies were 120 (28%), 100 (83%) of whom had a G8 score <14. Systemic therapy was administered to 336 patients (78%). At a median follow up of 7.2 months (range 1 to 52) 101 pts (24%) were dead. Median overall survival (mOS) was 27 months (1-52+).Patients with solid tumors, classified as frail by a G8 score <14 had a 3-fold risk of death compared with those with G8 > 14 (OR 3.26, CI 95 1.5-7.2, p = 0.003). Conversely, this increased risk was not observed in hematological malignancies (OR 1.4, CI 95 0.4-4.6, p = 0.57). By multivariate analysis, G8 score was associated with a worse prognosis only in patients with solid tumors. Conclusions: Our analysis suggest that elderly frail patients with solid tumors have a significantly increased risk of death as compared to elderly fit patients. Conversely, no impact of frailty, as assessed by a G8 score < 14, was evident in elderly patients with hematological malignancies.

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