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Anthony Dowling - One of the best experts on this subject based on the ideXlab platform.
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the utility of routine pre chemotherapy screening with cardiac gated blood pool scan for patients at low risk of Anthracycline Toxicity
Journal of Oncology Pharmacy Practice, 2018Co-Authors: Puey Ling Chia, K Chiang, R D Snyder, Anthony DowlingAbstract:Background Anthracycline-based chemotherapy is used in many malignancies. Current recommendations by several groups suggest cardiac monitoring prior to and during Anthracycline therapy. We aim to review the usefulness of baseline cardiac screening for left ventricular ejection fraction to assess if it had any impact on chemotherapy decisions in patients to be treated with Anthracycline-based regimens or any beneficial effect upon outcomes. Methods We conducted a retrospective three-year audit of cancer patients who underwent GBPS prior to Anthracycline (doxorubicin) chemotherapy. Subjects were identified via records from the Department of Nuclear Medicine. Pharmacy dispensing records identified those who received doxorubicin. Patient demographics, cancer type, cardiac risk factors, GBPS ejection fraction (EF), and cumulative Anthracycline dose were collected. Results From 1 August 2009 to 31 July 2012, 179 patients underwent GBPS pre-doxorubicin chemotherapy. The mean age was 59 years (range 21-89 years), with 51% being males. Only two patients (1.1%) had an abnormal EF < 50%, while 33 patients (18%) had an EF 51-59% and 144 patients (80%) had EF ≥ 60%. The two patients with reduced baseline EF still received Anthracycline-based chemotherapy. All 135 patients without any known cardiovascular risk factors had normal EFs. The total number of patients who received Anthracycline chemotherapy during the same period was 207. Thus 28 patients (13%) commenced Anthracycline without a prior GBPS. Conclusion Only 1.1% of the screened patients had EF < 50%. These two patients still received doxorubicin chemotherapy despite a compromised EF, as their treating clinicians believed that the benefits of chemotherapy outweighed the risk of potential cardiac Toxicity. Our audit questions the practice of routine cardiac evaluation pre-Anthracycline screening with GBPS. We propose that routine screening only be requested if cardiac risk factors are present.
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The utility of routine pre-chemotherapy screening with cardiac gated blood pool scan for patients at low risk of Anthracycline Toxicity.
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2017Co-Authors: Puey Ling Chia, K Chiang, Raymond Snyder, Anthony DowlingAbstract:Background Anthracycline-based chemotherapy is used in many malignancies. Current recommendations by several groups suggest cardiac monitoring prior to and during Anthracycline therapy. We aim to review the usefulness of baseline cardiac screening for left ventricular ejection fraction to assess if it had any impact on chemotherapy decisions in patients to be treated with Anthracycline-based regimens or any beneficial effect upon outcomes. Methods We conducted a retrospective three-year audit of cancer patients who underwent GBPS prior to Anthracycline (doxorubicin) chemotherapy. Subjects were identified via records from the Department of Nuclear Medicine. Pharmacy dispensing records identified those who received doxorubicin. Patient demographics, cancer type, cardiac risk factors, GBPS ejection fraction (EF), and cumulative Anthracycline dose were collected. Results From 1 August 2009 to 31 July 2012, 179 patients underwent GBPS pre-doxorubicin chemotherapy. The mean age was 59 years (range 21-89 years), with 51% being males. Only two patients (1.1%) had an abnormal EF
Edward Agura - One of the best experts on this subject based on the ideXlab platform.
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Report of a Phase II Study of Clofarabine and Cytarabine in De Novo and Relapsed and Refractory AML Patients and in Selected Elderly Patients at High Risk for Anthracycline Toxicity
The oncologist, 2011Co-Authors: Edward Agura, Barry Cooper, Houston Holmes, Estil Vance, Robert Brian Berryman, Christopher Maisel, Giovanna Saracino, Mirjana Tadic-ovcina, Joseph FayAbstract:Purpose. To determine the efficacy and safety of clofarabine and cytarabine (Ara-C) in adult patients with relapsedorrefractoryacutemyeloidleukemia(AML)andin elderly patients with untreated AML and heart disease. Patients and Methods. Patients with relapsed/refractory AML and older patients for whom there was a concern over Toxicity from additional Anthracyclines received 5 days of clofarabine, 40 mg/m 2 per day i.v. over 1 hour, followed 4 hours later by Ara-C, 1,000 mg/m 2 per day i.v. over 2 hours. Results. Thirty patients were enrolled. The median agewas67years(range,38–82years)and18(60%)had received at least one prior therapy. Eleven (37%) patients had a history of cardiovascular disease and were considered to be at high risk for Anthracycline Toxicity. High-risk cytogenetic abnormalities were present in 14 (47%) patients. The overall response rate (complete remission [CR] plus partial remission) was 53%, includingaCRin14patients(47%).Responseswereobserved in all cytogenetic risk groups and in patients who had received up to five prior therapies. The median diseasefree survival interval was 9.5 months. The 30-day mortality rate was 20% (de novo AML, 8%; relapsed/ refractory AML, 28%). Of the 14 patients achieving a CR, half were able to proceed to curative hematopoietic stem cell transplantation. Conclusions. Clofarabine in combination with Ara-C is effective in both untreated and previously treated patients with AML. In addition, it represents a useful remission induction strategy to serve as a bridge to transplantation in older patients with AML. The Oncologist 2011;16:197–206
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Phase II study of clofarabine and cytosine arabinoside in adult patients with relapsed AML and in elderly patients with untreated AML who are at high risk of Anthracycline Toxicity
Journal of Clinical Oncology, 2007Co-Authors: Edward Agura, Barry Cooper, Houston Holmes, Robert Brian Berryman, Christopher Maisel, Joseph W. Fay, Arturo Molina, L. Pineiro, E.a. VanceAbstract:7064 Purpose: To evaluate the efficacy/safety of a novel AML regimen in elderly patients with heart disease or in patients with a contraindication to ‘standard‘ Anthracycline-containing regimens. Patients and Methods: Phase II, open-label design. Eligible pts had elderly de-novo or relapsed AML or would not benefit from 7+3 or simlar therapy. Treatment was CLOF 40 mg/m2, Ara-C 1,000 mg/m2. (d1–5). Results: Patients were accrued and treated from April 2005 through Oct 2006. All pts signed IRB-approved consents. The median age was 67 years (range 38–82 years). Twenty (67%) subjects had received at least one prior cytoxic regimen (excluding 5-AZA). Significant cardiovascular (history of MI, bypass grafting, cardiomyopathy) was present in 43% (13/30) prior to therapy. Thirty pts were enrolled and all recieved at least one day of therapy. 1 pt died within 24 hours of starting treatment due to disease progression. Of the remaining, 29/30 received at least one complete cycle of therapy and 5 received 2 cycles. N...
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Phase II Study of Clofarabine and Cytosine Arabinoside in Adult Patients with Relapsed AML and in Elderly Patients with Untreated AML Who Are at High Risk of Anthracycline Toxicity.
Blood, 2006Co-Authors: Edward Agura, Barry Cooper, Houston Holmes, Christopher Maisel, R. Brian Berryman, Laura Brougher, Andrew De Leon, Joseph W. Fay, Arturo Molina, L. PineiroAbstract:PURPOSE: To evaluate the efficacy and safety of clofarabine, a novel deoxyadenosine analog, in adult patients with refractory or relapsed acute myeloid leukemia and in selected elderly patients with untreated AML and heart disease. PATIENTS AND METHODS: In a phase II, open-label trial, 23 patients with de-novo AML, AML evolved from MDS or relapsed AML received a 5 day regimen consisting of clofarabine 40 mg/m2 intravenously over 1 hour followed within 4 hours by Ara-C 1000 mg/m2. The median age was 68 years (range 39–79 years). Fifteen (65%) had received at least one prior cytotoxic regimen (excluding 5-AZA). Significant cardiovascular disease (history of myocardial infarction, bypass grafting, cardiomyopathy) was present in 52% (12/23) prior to therapy. RESULTS: 22/23 received at least one cycle of therapy and 5 received 2 cycles. One early death was due to disease progression. Grade 4 neutropenia developed in all patients. There were no cases of regimen-related cardiac Toxicity. Most patients had some degree of edema and third-spacing syndrome. Several developed a significant but reversible acral rash. 20 patients are evaluable for response. The histologic response rate (defined as marrow blasts
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phase ii study of clofarabine and cytosine arabinoside in adult patients with relapsed aml and in elderly patients with untreated aml who are at high risk of Anthracycline Toxicity
Blood, 2006Co-Authors: Edward Agura, Barry Cooper, Houston Holmes, Christopher Maisel, Laura Brougher, Andrew De Leon, Joseph W. Fay, Arturo Molina, Brian R Berryman, L. PineiroAbstract:PURPOSE: To evaluate the efficacy and safety of clofarabine, a novel deoxyadenosine analog, in adult patients with refractory or relapsed acute myeloid leukemia and in selected elderly patients with untreated AML and heart disease. PATIENTS AND METHODS: In a phase II, open-label trial, 23 patients with de-novo AML, AML evolved from MDS or relapsed AML received a 5 day regimen consisting of clofarabine 40 mg/m2 intravenously over 1 hour followed within 4 hours by Ara-C 1000 mg/m2. The median age was 68 years (range 39–79 years). Fifteen (65%) had received at least one prior cytotoxic regimen (excluding 5-AZA). Significant cardiovascular disease (history of myocardial infarction, bypass grafting, cardiomyopathy) was present in 52% (12/23) prior to therapy. RESULTS: 22/23 received at least one cycle of therapy and 5 received 2 cycles. One early death was due to disease progression. Grade 4 neutropenia developed in all patients. There were no cases of regimen-related cardiac Toxicity. Most patients had some degree of edema and third-spacing syndrome. Several developed a significant but reversible acral rash. 20 patients are evaluable for response. The histologic response rate (defined as marrow blasts <5%) is 60% (12/20) consisting of 10 (50%) complete remissions and 2 (10%) partial responses. Complete cytogenetic remissions occurred in 9 patients. Durable remissions and low Toxicity allowed some patients to proceed to nonablative allogeneic stem cell transplantation. CONCLUSION: Clofarabine (40mg/m2) and Ara-C (1000mg/m2) x 5 days is an active and well tolerated regimen in myeloid malignancies including “elderly AML”—a distinct entity usually associated with poor response rate and high treatment-related toxicities. Other drug combinations with clofarabine are being explored for use in allogeneic transplant regimens and with other high-risk patient groups.
Puey Ling Chia - One of the best experts on this subject based on the ideXlab platform.
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the utility of routine pre chemotherapy screening with cardiac gated blood pool scan for patients at low risk of Anthracycline Toxicity
Journal of Oncology Pharmacy Practice, 2018Co-Authors: Puey Ling Chia, K Chiang, R D Snyder, Anthony DowlingAbstract:Background Anthracycline-based chemotherapy is used in many malignancies. Current recommendations by several groups suggest cardiac monitoring prior to and during Anthracycline therapy. We aim to review the usefulness of baseline cardiac screening for left ventricular ejection fraction to assess if it had any impact on chemotherapy decisions in patients to be treated with Anthracycline-based regimens or any beneficial effect upon outcomes. Methods We conducted a retrospective three-year audit of cancer patients who underwent GBPS prior to Anthracycline (doxorubicin) chemotherapy. Subjects were identified via records from the Department of Nuclear Medicine. Pharmacy dispensing records identified those who received doxorubicin. Patient demographics, cancer type, cardiac risk factors, GBPS ejection fraction (EF), and cumulative Anthracycline dose were collected. Results From 1 August 2009 to 31 July 2012, 179 patients underwent GBPS pre-doxorubicin chemotherapy. The mean age was 59 years (range 21-89 years), with 51% being males. Only two patients (1.1%) had an abnormal EF < 50%, while 33 patients (18%) had an EF 51-59% and 144 patients (80%) had EF ≥ 60%. The two patients with reduced baseline EF still received Anthracycline-based chemotherapy. All 135 patients without any known cardiovascular risk factors had normal EFs. The total number of patients who received Anthracycline chemotherapy during the same period was 207. Thus 28 patients (13%) commenced Anthracycline without a prior GBPS. Conclusion Only 1.1% of the screened patients had EF < 50%. These two patients still received doxorubicin chemotherapy despite a compromised EF, as their treating clinicians believed that the benefits of chemotherapy outweighed the risk of potential cardiac Toxicity. Our audit questions the practice of routine cardiac evaluation pre-Anthracycline screening with GBPS. We propose that routine screening only be requested if cardiac risk factors are present.
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The utility of routine pre-chemotherapy screening with cardiac gated blood pool scan for patients at low risk of Anthracycline Toxicity.
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2017Co-Authors: Puey Ling Chia, K Chiang, Raymond Snyder, Anthony DowlingAbstract:Background Anthracycline-based chemotherapy is used in many malignancies. Current recommendations by several groups suggest cardiac monitoring prior to and during Anthracycline therapy. We aim to review the usefulness of baseline cardiac screening for left ventricular ejection fraction to assess if it had any impact on chemotherapy decisions in patients to be treated with Anthracycline-based regimens or any beneficial effect upon outcomes. Methods We conducted a retrospective three-year audit of cancer patients who underwent GBPS prior to Anthracycline (doxorubicin) chemotherapy. Subjects were identified via records from the Department of Nuclear Medicine. Pharmacy dispensing records identified those who received doxorubicin. Patient demographics, cancer type, cardiac risk factors, GBPS ejection fraction (EF), and cumulative Anthracycline dose were collected. Results From 1 August 2009 to 31 July 2012, 179 patients underwent GBPS pre-doxorubicin chemotherapy. The mean age was 59 years (range 21-89 years), with 51% being males. Only two patients (1.1%) had an abnormal EF
Christopher Maisel - One of the best experts on this subject based on the ideXlab platform.
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Report of a Phase II Study of Clofarabine and Cytarabine in De Novo and Relapsed and Refractory AML Patients and in Selected Elderly Patients at High Risk for Anthracycline Toxicity
The oncologist, 2011Co-Authors: Edward Agura, Barry Cooper, Houston Holmes, Estil Vance, Robert Brian Berryman, Christopher Maisel, Giovanna Saracino, Mirjana Tadic-ovcina, Joseph FayAbstract:Purpose. To determine the efficacy and safety of clofarabine and cytarabine (Ara-C) in adult patients with relapsedorrefractoryacutemyeloidleukemia(AML)andin elderly patients with untreated AML and heart disease. Patients and Methods. Patients with relapsed/refractory AML and older patients for whom there was a concern over Toxicity from additional Anthracyclines received 5 days of clofarabine, 40 mg/m 2 per day i.v. over 1 hour, followed 4 hours later by Ara-C, 1,000 mg/m 2 per day i.v. over 2 hours. Results. Thirty patients were enrolled. The median agewas67years(range,38–82years)and18(60%)had received at least one prior therapy. Eleven (37%) patients had a history of cardiovascular disease and were considered to be at high risk for Anthracycline Toxicity. High-risk cytogenetic abnormalities were present in 14 (47%) patients. The overall response rate (complete remission [CR] plus partial remission) was 53%, includingaCRin14patients(47%).Responseswereobserved in all cytogenetic risk groups and in patients who had received up to five prior therapies. The median diseasefree survival interval was 9.5 months. The 30-day mortality rate was 20% (de novo AML, 8%; relapsed/ refractory AML, 28%). Of the 14 patients achieving a CR, half were able to proceed to curative hematopoietic stem cell transplantation. Conclusions. Clofarabine in combination with Ara-C is effective in both untreated and previously treated patients with AML. In addition, it represents a useful remission induction strategy to serve as a bridge to transplantation in older patients with AML. The Oncologist 2011;16:197–206
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Phase II study of clofarabine and cytosine arabinoside in adult patients with relapsed AML and in elderly patients with untreated AML who are at high risk of Anthracycline Toxicity
Journal of Clinical Oncology, 2007Co-Authors: Edward Agura, Barry Cooper, Houston Holmes, Robert Brian Berryman, Christopher Maisel, Joseph W. Fay, Arturo Molina, L. Pineiro, E.a. VanceAbstract:7064 Purpose: To evaluate the efficacy/safety of a novel AML regimen in elderly patients with heart disease or in patients with a contraindication to ‘standard‘ Anthracycline-containing regimens. Patients and Methods: Phase II, open-label design. Eligible pts had elderly de-novo or relapsed AML or would not benefit from 7+3 or simlar therapy. Treatment was CLOF 40 mg/m2, Ara-C 1,000 mg/m2. (d1–5). Results: Patients were accrued and treated from April 2005 through Oct 2006. All pts signed IRB-approved consents. The median age was 67 years (range 38–82 years). Twenty (67%) subjects had received at least one prior cytoxic regimen (excluding 5-AZA). Significant cardiovascular (history of MI, bypass grafting, cardiomyopathy) was present in 43% (13/30) prior to therapy. Thirty pts were enrolled and all recieved at least one day of therapy. 1 pt died within 24 hours of starting treatment due to disease progression. Of the remaining, 29/30 received at least one complete cycle of therapy and 5 received 2 cycles. N...
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Phase II Study of Clofarabine and Cytosine Arabinoside in Adult Patients with Relapsed AML and in Elderly Patients with Untreated AML Who Are at High Risk of Anthracycline Toxicity.
Blood, 2006Co-Authors: Edward Agura, Barry Cooper, Houston Holmes, Christopher Maisel, R. Brian Berryman, Laura Brougher, Andrew De Leon, Joseph W. Fay, Arturo Molina, L. PineiroAbstract:PURPOSE: To evaluate the efficacy and safety of clofarabine, a novel deoxyadenosine analog, in adult patients with refractory or relapsed acute myeloid leukemia and in selected elderly patients with untreated AML and heart disease. PATIENTS AND METHODS: In a phase II, open-label trial, 23 patients with de-novo AML, AML evolved from MDS or relapsed AML received a 5 day regimen consisting of clofarabine 40 mg/m2 intravenously over 1 hour followed within 4 hours by Ara-C 1000 mg/m2. The median age was 68 years (range 39–79 years). Fifteen (65%) had received at least one prior cytotoxic regimen (excluding 5-AZA). Significant cardiovascular disease (history of myocardial infarction, bypass grafting, cardiomyopathy) was present in 52% (12/23) prior to therapy. RESULTS: 22/23 received at least one cycle of therapy and 5 received 2 cycles. One early death was due to disease progression. Grade 4 neutropenia developed in all patients. There were no cases of regimen-related cardiac Toxicity. Most patients had some degree of edema and third-spacing syndrome. Several developed a significant but reversible acral rash. 20 patients are evaluable for response. The histologic response rate (defined as marrow blasts
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phase ii study of clofarabine and cytosine arabinoside in adult patients with relapsed aml and in elderly patients with untreated aml who are at high risk of Anthracycline Toxicity
Blood, 2006Co-Authors: Edward Agura, Barry Cooper, Houston Holmes, Christopher Maisel, Laura Brougher, Andrew De Leon, Joseph W. Fay, Arturo Molina, Brian R Berryman, L. PineiroAbstract:PURPOSE: To evaluate the efficacy and safety of clofarabine, a novel deoxyadenosine analog, in adult patients with refractory or relapsed acute myeloid leukemia and in selected elderly patients with untreated AML and heart disease. PATIENTS AND METHODS: In a phase II, open-label trial, 23 patients with de-novo AML, AML evolved from MDS or relapsed AML received a 5 day regimen consisting of clofarabine 40 mg/m2 intravenously over 1 hour followed within 4 hours by Ara-C 1000 mg/m2. The median age was 68 years (range 39–79 years). Fifteen (65%) had received at least one prior cytotoxic regimen (excluding 5-AZA). Significant cardiovascular disease (history of myocardial infarction, bypass grafting, cardiomyopathy) was present in 52% (12/23) prior to therapy. RESULTS: 22/23 received at least one cycle of therapy and 5 received 2 cycles. One early death was due to disease progression. Grade 4 neutropenia developed in all patients. There were no cases of regimen-related cardiac Toxicity. Most patients had some degree of edema and third-spacing syndrome. Several developed a significant but reversible acral rash. 20 patients are evaluable for response. The histologic response rate (defined as marrow blasts <5%) is 60% (12/20) consisting of 10 (50%) complete remissions and 2 (10%) partial responses. Complete cytogenetic remissions occurred in 9 patients. Durable remissions and low Toxicity allowed some patients to proceed to nonablative allogeneic stem cell transplantation. CONCLUSION: Clofarabine (40mg/m2) and Ara-C (1000mg/m2) x 5 days is an active and well tolerated regimen in myeloid malignancies including “elderly AML”—a distinct entity usually associated with poor response rate and high treatment-related toxicities. Other drug combinations with clofarabine are being explored for use in allogeneic transplant regimens and with other high-risk patient groups.
Houston Holmes - One of the best experts on this subject based on the ideXlab platform.
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Report of a Phase II Study of Clofarabine and Cytarabine in De Novo and Relapsed and Refractory AML Patients and in Selected Elderly Patients at High Risk for Anthracycline Toxicity
The oncologist, 2011Co-Authors: Edward Agura, Barry Cooper, Houston Holmes, Estil Vance, Robert Brian Berryman, Christopher Maisel, Giovanna Saracino, Mirjana Tadic-ovcina, Joseph FayAbstract:Purpose. To determine the efficacy and safety of clofarabine and cytarabine (Ara-C) in adult patients with relapsedorrefractoryacutemyeloidleukemia(AML)andin elderly patients with untreated AML and heart disease. Patients and Methods. Patients with relapsed/refractory AML and older patients for whom there was a concern over Toxicity from additional Anthracyclines received 5 days of clofarabine, 40 mg/m 2 per day i.v. over 1 hour, followed 4 hours later by Ara-C, 1,000 mg/m 2 per day i.v. over 2 hours. Results. Thirty patients were enrolled. The median agewas67years(range,38–82years)and18(60%)had received at least one prior therapy. Eleven (37%) patients had a history of cardiovascular disease and were considered to be at high risk for Anthracycline Toxicity. High-risk cytogenetic abnormalities were present in 14 (47%) patients. The overall response rate (complete remission [CR] plus partial remission) was 53%, includingaCRin14patients(47%).Responseswereobserved in all cytogenetic risk groups and in patients who had received up to five prior therapies. The median diseasefree survival interval was 9.5 months. The 30-day mortality rate was 20% (de novo AML, 8%; relapsed/ refractory AML, 28%). Of the 14 patients achieving a CR, half were able to proceed to curative hematopoietic stem cell transplantation. Conclusions. Clofarabine in combination with Ara-C is effective in both untreated and previously treated patients with AML. In addition, it represents a useful remission induction strategy to serve as a bridge to transplantation in older patients with AML. The Oncologist 2011;16:197–206
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Phase II study of clofarabine and cytosine arabinoside in adult patients with relapsed AML and in elderly patients with untreated AML who are at high risk of Anthracycline Toxicity
Journal of Clinical Oncology, 2007Co-Authors: Edward Agura, Barry Cooper, Houston Holmes, Robert Brian Berryman, Christopher Maisel, Joseph W. Fay, Arturo Molina, L. Pineiro, E.a. VanceAbstract:7064 Purpose: To evaluate the efficacy/safety of a novel AML regimen in elderly patients with heart disease or in patients with a contraindication to ‘standard‘ Anthracycline-containing regimens. Patients and Methods: Phase II, open-label design. Eligible pts had elderly de-novo or relapsed AML or would not benefit from 7+3 or simlar therapy. Treatment was CLOF 40 mg/m2, Ara-C 1,000 mg/m2. (d1–5). Results: Patients were accrued and treated from April 2005 through Oct 2006. All pts signed IRB-approved consents. The median age was 67 years (range 38–82 years). Twenty (67%) subjects had received at least one prior cytoxic regimen (excluding 5-AZA). Significant cardiovascular (history of MI, bypass grafting, cardiomyopathy) was present in 43% (13/30) prior to therapy. Thirty pts were enrolled and all recieved at least one day of therapy. 1 pt died within 24 hours of starting treatment due to disease progression. Of the remaining, 29/30 received at least one complete cycle of therapy and 5 received 2 cycles. N...
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Phase II Study of Clofarabine and Cytosine Arabinoside in Adult Patients with Relapsed AML and in Elderly Patients with Untreated AML Who Are at High Risk of Anthracycline Toxicity.
Blood, 2006Co-Authors: Edward Agura, Barry Cooper, Houston Holmes, Christopher Maisel, R. Brian Berryman, Laura Brougher, Andrew De Leon, Joseph W. Fay, Arturo Molina, L. PineiroAbstract:PURPOSE: To evaluate the efficacy and safety of clofarabine, a novel deoxyadenosine analog, in adult patients with refractory or relapsed acute myeloid leukemia and in selected elderly patients with untreated AML and heart disease. PATIENTS AND METHODS: In a phase II, open-label trial, 23 patients with de-novo AML, AML evolved from MDS or relapsed AML received a 5 day regimen consisting of clofarabine 40 mg/m2 intravenously over 1 hour followed within 4 hours by Ara-C 1000 mg/m2. The median age was 68 years (range 39–79 years). Fifteen (65%) had received at least one prior cytotoxic regimen (excluding 5-AZA). Significant cardiovascular disease (history of myocardial infarction, bypass grafting, cardiomyopathy) was present in 52% (12/23) prior to therapy. RESULTS: 22/23 received at least one cycle of therapy and 5 received 2 cycles. One early death was due to disease progression. Grade 4 neutropenia developed in all patients. There were no cases of regimen-related cardiac Toxicity. Most patients had some degree of edema and third-spacing syndrome. Several developed a significant but reversible acral rash. 20 patients are evaluable for response. The histologic response rate (defined as marrow blasts
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phase ii study of clofarabine and cytosine arabinoside in adult patients with relapsed aml and in elderly patients with untreated aml who are at high risk of Anthracycline Toxicity
Blood, 2006Co-Authors: Edward Agura, Barry Cooper, Houston Holmes, Christopher Maisel, Laura Brougher, Andrew De Leon, Joseph W. Fay, Arturo Molina, Brian R Berryman, L. PineiroAbstract:PURPOSE: To evaluate the efficacy and safety of clofarabine, a novel deoxyadenosine analog, in adult patients with refractory or relapsed acute myeloid leukemia and in selected elderly patients with untreated AML and heart disease. PATIENTS AND METHODS: In a phase II, open-label trial, 23 patients with de-novo AML, AML evolved from MDS or relapsed AML received a 5 day regimen consisting of clofarabine 40 mg/m2 intravenously over 1 hour followed within 4 hours by Ara-C 1000 mg/m2. The median age was 68 years (range 39–79 years). Fifteen (65%) had received at least one prior cytotoxic regimen (excluding 5-AZA). Significant cardiovascular disease (history of myocardial infarction, bypass grafting, cardiomyopathy) was present in 52% (12/23) prior to therapy. RESULTS: 22/23 received at least one cycle of therapy and 5 received 2 cycles. One early death was due to disease progression. Grade 4 neutropenia developed in all patients. There were no cases of regimen-related cardiac Toxicity. Most patients had some degree of edema and third-spacing syndrome. Several developed a significant but reversible acral rash. 20 patients are evaluable for response. The histologic response rate (defined as marrow blasts <5%) is 60% (12/20) consisting of 10 (50%) complete remissions and 2 (10%) partial responses. Complete cytogenetic remissions occurred in 9 patients. Durable remissions and low Toxicity allowed some patients to proceed to nonablative allogeneic stem cell transplantation. CONCLUSION: Clofarabine (40mg/m2) and Ara-C (1000mg/m2) x 5 days is an active and well tolerated regimen in myeloid malignancies including “elderly AML”—a distinct entity usually associated with poor response rate and high treatment-related toxicities. Other drug combinations with clofarabine are being explored for use in allogeneic transplant regimens and with other high-risk patient groups.