MYELOTOXICITY OF PEPTIDE RECEPTOR RADIONUCLIDE THERAPY OF NEUROENDOCRINE TUMORS: A DECADE OF EXPERIENCE
(Abstract release date: 05/19/16)
EHA Library. Kesavan M. 06/09/16; 134829; PB1929
Dr. Murali Kesavan
Contributions
Contributions
Abstract
Abstract: PB1929
Type: Publication Only
Background
Myelodysplastic syndrome (MDS) and acute leukemia (AL) have been associated with peptide receptor radionuclide therapy (PRRT) in heavily pre-treated patients with a prior history of exposure to alkylating agents. Commenced 15 years ago PRRT is now becoming established as first and second line therapy for gastrointestinal and pancreatic neuroendocrine tumors (GEPNETS). Current therapies gain only marginal, albeit statistically significant, increase in progression free survival (PFS) without meaningful objective responses and are accompanied by significant toxicity. With the incidence of GEPNETS rising in the Western world, myelotoxicity is now the most significant potential adverse event following PRRT.
Aims
This review of the literature, and our own decade of experience with lutetium-177-octreotate-capecitabine +/- temozolamide PRRT-chemotherapy of GEPNETS analyses the risk of both short and long-term hematotoxicity.
Methods
All of the literature on myelotoxicity in associated with PRRT of NETS reported in papers published over the past 15 years has been reviewed and compared with our own experience of lutetium-177 PRRT combined with octreotate-capecitabine-temozolomide radiosensitising chemotherapy. Relevant primary research concerning myelotoxicity and PRRT was identified using medical databases. Key articles published from 2000 onwards were obtained primarily from PubMed, Ovid and Cochrane databases. Specific focus was given to articles published in Cancer Biotherapy and Radiopharmaceuticals, European Journal of Nuclear Medicine and Molecular imaging, Neuroendocrinology, Journal of Clinical Oncology and Endocrine Related Cancer.
Results
Sixteen key articles involving primary research were identified; 12 articles relating to PRRT as monotherapy and 4 articles relating to PRRT in combination with chemotherapy and/or novel agents. A total of 2225 patients were treated (2104 treated with PRRT monotherapy and 121 with PRRT combination) all of whom had been exposed to prior therapies, including somatostatin analogs, alkylating agents, radiotherapy, prior PRRT and surgery with the majority having had exposure to greater than two prior lines of treatment. The average age of patients in these studies ranged from 53 to 64 years with median duration of follow up ranging from 6 to 62 months. Short-term myelotoxicity was observed in 221 patients (10%), occuring in 213 of 2104 patients treated with PRRT monotherapy and 8 of 121 patients treated with PRRT combination. Acute toxicity manifested as modest self-limited grade 3/4 toxicity (CTCAE or WHO) most often affecting platelets then WBC and lastly hemoglobin, and was commonly observed during the first cycle of treatment, with the lowest nadir predictive of time taken for recovery. Toxicity manifesting early was easily managed with dose modification or therapy cessation, and was ameliorated by appropriate patient selection based on age, prior therapies, comorbidities and adequate baseline myeloid function. Long-term toxicity in the form of MDS and AL was a rare stochastic event occurring in only 32 (1.4%) of all the patients treated with PRRT (24 cases of MDS, 6 cases of MDS with subsequent transformation to AL and 2 cases of AL alone). Where bone marrow biopsy was performed the majority of cases of MDS displayed complex cytogenetic abnormalities, consistent with secondary MDS following exposure to chemotherapy with alkylating agents or irradiation. The development of MDS was a risk factor for AL. No significant difference in relative risk of MDS/AL was noted between patients salvaged with PRRT monotherapy or PRRT combination (1.4% and 1.6% respectively). Factors associated with development of significant short and long-term myelotoxicity included age >70 years, impaired renal function, baseline cytopenias, prior number of therapies, prior chemotherapy (especially alkylating agents) and prior radiation therapy. The latter two factors were associated with a significant of development of MDS and AL.
Conclusion
Early therapy with PRRT-containing regimens improves outcomes, minimizes myelotoxicity and renders the risk of MDS and AL negligible.
Session topic: E-poster
Keyword(s): Cancer, Hematotoxicity, MDS/AML, Radioimmunotherapy
Type: Publication Only
Background
Myelodysplastic syndrome (MDS) and acute leukemia (AL) have been associated with peptide receptor radionuclide therapy (PRRT) in heavily pre-treated patients with a prior history of exposure to alkylating agents. Commenced 15 years ago PRRT is now becoming established as first and second line therapy for gastrointestinal and pancreatic neuroendocrine tumors (GEPNETS). Current therapies gain only marginal, albeit statistically significant, increase in progression free survival (PFS) without meaningful objective responses and are accompanied by significant toxicity. With the incidence of GEPNETS rising in the Western world, myelotoxicity is now the most significant potential adverse event following PRRT.
Aims
This review of the literature, and our own decade of experience with lutetium-177-octreotate-capecitabine +/- temozolamide PRRT-chemotherapy of GEPNETS analyses the risk of both short and long-term hematotoxicity.
Methods
All of the literature on myelotoxicity in associated with PRRT of NETS reported in papers published over the past 15 years has been reviewed and compared with our own experience of lutetium-177 PRRT combined with octreotate-capecitabine-temozolomide radiosensitising chemotherapy. Relevant primary research concerning myelotoxicity and PRRT was identified using medical databases. Key articles published from 2000 onwards were obtained primarily from PubMed, Ovid and Cochrane databases. Specific focus was given to articles published in Cancer Biotherapy and Radiopharmaceuticals, European Journal of Nuclear Medicine and Molecular imaging, Neuroendocrinology, Journal of Clinical Oncology and Endocrine Related Cancer.
Results
Sixteen key articles involving primary research were identified; 12 articles relating to PRRT as monotherapy and 4 articles relating to PRRT in combination with chemotherapy and/or novel agents. A total of 2225 patients were treated (2104 treated with PRRT monotherapy and 121 with PRRT combination) all of whom had been exposed to prior therapies, including somatostatin analogs, alkylating agents, radiotherapy, prior PRRT and surgery with the majority having had exposure to greater than two prior lines of treatment. The average age of patients in these studies ranged from 53 to 64 years with median duration of follow up ranging from 6 to 62 months. Short-term myelotoxicity was observed in 221 patients (10%), occuring in 213 of 2104 patients treated with PRRT monotherapy and 8 of 121 patients treated with PRRT combination. Acute toxicity manifested as modest self-limited grade 3/4 toxicity (CTCAE or WHO) most often affecting platelets then WBC and lastly hemoglobin, and was commonly observed during the first cycle of treatment, with the lowest nadir predictive of time taken for recovery. Toxicity manifesting early was easily managed with dose modification or therapy cessation, and was ameliorated by appropriate patient selection based on age, prior therapies, comorbidities and adequate baseline myeloid function. Long-term toxicity in the form of MDS and AL was a rare stochastic event occurring in only 32 (1.4%) of all the patients treated with PRRT (24 cases of MDS, 6 cases of MDS with subsequent transformation to AL and 2 cases of AL alone). Where bone marrow biopsy was performed the majority of cases of MDS displayed complex cytogenetic abnormalities, consistent with secondary MDS following exposure to chemotherapy with alkylating agents or irradiation. The development of MDS was a risk factor for AL. No significant difference in relative risk of MDS/AL was noted between patients salvaged with PRRT monotherapy or PRRT combination (1.4% and 1.6% respectively). Factors associated with development of significant short and long-term myelotoxicity included age >70 years, impaired renal function, baseline cytopenias, prior number of therapies, prior chemotherapy (especially alkylating agents) and prior radiation therapy. The latter two factors were associated with a significant of development of MDS and AL.
Conclusion
Early therapy with PRRT-containing regimens improves outcomes, minimizes myelotoxicity and renders the risk of MDS and AL negligible.
Session topic: E-poster
Keyword(s): Cancer, Hematotoxicity, MDS/AML, Radioimmunotherapy
Abstract: PB1929
Type: Publication Only
Background
Myelodysplastic syndrome (MDS) and acute leukemia (AL) have been associated with peptide receptor radionuclide therapy (PRRT) in heavily pre-treated patients with a prior history of exposure to alkylating agents. Commenced 15 years ago PRRT is now becoming established as first and second line therapy for gastrointestinal and pancreatic neuroendocrine tumors (GEPNETS). Current therapies gain only marginal, albeit statistically significant, increase in progression free survival (PFS) without meaningful objective responses and are accompanied by significant toxicity. With the incidence of GEPNETS rising in the Western world, myelotoxicity is now the most significant potential adverse event following PRRT.
Aims
This review of the literature, and our own decade of experience with lutetium-177-octreotate-capecitabine +/- temozolamide PRRT-chemotherapy of GEPNETS analyses the risk of both short and long-term hematotoxicity.
Methods
All of the literature on myelotoxicity in associated with PRRT of NETS reported in papers published over the past 15 years has been reviewed and compared with our own experience of lutetium-177 PRRT combined with octreotate-capecitabine-temozolomide radiosensitising chemotherapy. Relevant primary research concerning myelotoxicity and PRRT was identified using medical databases. Key articles published from 2000 onwards were obtained primarily from PubMed, Ovid and Cochrane databases. Specific focus was given to articles published in Cancer Biotherapy and Radiopharmaceuticals, European Journal of Nuclear Medicine and Molecular imaging, Neuroendocrinology, Journal of Clinical Oncology and Endocrine Related Cancer.
Results
Sixteen key articles involving primary research were identified; 12 articles relating to PRRT as monotherapy and 4 articles relating to PRRT in combination with chemotherapy and/or novel agents. A total of 2225 patients were treated (2104 treated with PRRT monotherapy and 121 with PRRT combination) all of whom had been exposed to prior therapies, including somatostatin analogs, alkylating agents, radiotherapy, prior PRRT and surgery with the majority having had exposure to greater than two prior lines of treatment. The average age of patients in these studies ranged from 53 to 64 years with median duration of follow up ranging from 6 to 62 months. Short-term myelotoxicity was observed in 221 patients (10%), occuring in 213 of 2104 patients treated with PRRT monotherapy and 8 of 121 patients treated with PRRT combination. Acute toxicity manifested as modest self-limited grade 3/4 toxicity (CTCAE or WHO) most often affecting platelets then WBC and lastly hemoglobin, and was commonly observed during the first cycle of treatment, with the lowest nadir predictive of time taken for recovery. Toxicity manifesting early was easily managed with dose modification or therapy cessation, and was ameliorated by appropriate patient selection based on age, prior therapies, comorbidities and adequate baseline myeloid function. Long-term toxicity in the form of MDS and AL was a rare stochastic event occurring in only 32 (1.4%) of all the patients treated with PRRT (24 cases of MDS, 6 cases of MDS with subsequent transformation to AL and 2 cases of AL alone). Where bone marrow biopsy was performed the majority of cases of MDS displayed complex cytogenetic abnormalities, consistent with secondary MDS following exposure to chemotherapy with alkylating agents or irradiation. The development of MDS was a risk factor for AL. No significant difference in relative risk of MDS/AL was noted between patients salvaged with PRRT monotherapy or PRRT combination (1.4% and 1.6% respectively). Factors associated with development of significant short and long-term myelotoxicity included age >70 years, impaired renal function, baseline cytopenias, prior number of therapies, prior chemotherapy (especially alkylating agents) and prior radiation therapy. The latter two factors were associated with a significant of development of MDS and AL.
Conclusion
Early therapy with PRRT-containing regimens improves outcomes, minimizes myelotoxicity and renders the risk of MDS and AL negligible.
Session topic: E-poster
Keyword(s): Cancer, Hematotoxicity, MDS/AML, Radioimmunotherapy
Type: Publication Only
Background
Myelodysplastic syndrome (MDS) and acute leukemia (AL) have been associated with peptide receptor radionuclide therapy (PRRT) in heavily pre-treated patients with a prior history of exposure to alkylating agents. Commenced 15 years ago PRRT is now becoming established as first and second line therapy for gastrointestinal and pancreatic neuroendocrine tumors (GEPNETS). Current therapies gain only marginal, albeit statistically significant, increase in progression free survival (PFS) without meaningful objective responses and are accompanied by significant toxicity. With the incidence of GEPNETS rising in the Western world, myelotoxicity is now the most significant potential adverse event following PRRT.
Aims
This review of the literature, and our own decade of experience with lutetium-177-octreotate-capecitabine +/- temozolamide PRRT-chemotherapy of GEPNETS analyses the risk of both short and long-term hematotoxicity.
Methods
All of the literature on myelotoxicity in associated with PRRT of NETS reported in papers published over the past 15 years has been reviewed and compared with our own experience of lutetium-177 PRRT combined with octreotate-capecitabine-temozolomide radiosensitising chemotherapy. Relevant primary research concerning myelotoxicity and PRRT was identified using medical databases. Key articles published from 2000 onwards were obtained primarily from PubMed, Ovid and Cochrane databases. Specific focus was given to articles published in Cancer Biotherapy and Radiopharmaceuticals, European Journal of Nuclear Medicine and Molecular imaging, Neuroendocrinology, Journal of Clinical Oncology and Endocrine Related Cancer.
Results
Sixteen key articles involving primary research were identified; 12 articles relating to PRRT as monotherapy and 4 articles relating to PRRT in combination with chemotherapy and/or novel agents. A total of 2225 patients were treated (2104 treated with PRRT monotherapy and 121 with PRRT combination) all of whom had been exposed to prior therapies, including somatostatin analogs, alkylating agents, radiotherapy, prior PRRT and surgery with the majority having had exposure to greater than two prior lines of treatment. The average age of patients in these studies ranged from 53 to 64 years with median duration of follow up ranging from 6 to 62 months. Short-term myelotoxicity was observed in 221 patients (10%), occuring in 213 of 2104 patients treated with PRRT monotherapy and 8 of 121 patients treated with PRRT combination. Acute toxicity manifested as modest self-limited grade 3/4 toxicity (CTCAE or WHO) most often affecting platelets then WBC and lastly hemoglobin, and was commonly observed during the first cycle of treatment, with the lowest nadir predictive of time taken for recovery. Toxicity manifesting early was easily managed with dose modification or therapy cessation, and was ameliorated by appropriate patient selection based on age, prior therapies, comorbidities and adequate baseline myeloid function. Long-term toxicity in the form of MDS and AL was a rare stochastic event occurring in only 32 (1.4%) of all the patients treated with PRRT (24 cases of MDS, 6 cases of MDS with subsequent transformation to AL and 2 cases of AL alone). Where bone marrow biopsy was performed the majority of cases of MDS displayed complex cytogenetic abnormalities, consistent with secondary MDS following exposure to chemotherapy with alkylating agents or irradiation. The development of MDS was a risk factor for AL. No significant difference in relative risk of MDS/AL was noted between patients salvaged with PRRT monotherapy or PRRT combination (1.4% and 1.6% respectively). Factors associated with development of significant short and long-term myelotoxicity included age >70 years, impaired renal function, baseline cytopenias, prior number of therapies, prior chemotherapy (especially alkylating agents) and prior radiation therapy. The latter two factors were associated with a significant of development of MDS and AL.
Conclusion
Early therapy with PRRT-containing regimens improves outcomes, minimizes myelotoxicity and renders the risk of MDS and AL negligible.
Session topic: E-poster
Keyword(s): Cancer, Hematotoxicity, MDS/AML, Radioimmunotherapy
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