March 14, 2011 (Hollywood, Florida) — Guidance of the National Comprehensive Cancer Network (NCCN) on the use of myeloid growth factors did not change much from 2010 to 2011. However, one change — a revised footnote — had enough impact to occupy a large chunk of an hour-long talk that updated and reviewed the guideline at the NCCN 16th Annual Conference.
There is a "slight excess risk" of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) in patients treated with colony-stimulating factors (CSF) for the prevention of febrile neutropenia associated with chemotherapy, the footnote says.
The content of the footnote is derived from a systematic review of randomized clinical trials of cancer patients receiving chemotherapy with or without primary G (granulocyte)-CSF support. With G-CSF use, there was a nearly 2-fold relative risk increase (1.92) and an absolute risk increase of 0.41% for AML/MDS; the average length of follow-up was 2 years.
On the plus side of the systematic review's findings, there was a reduction in all-cause mortality in patients treated with G-CSF. Specifically, in patients who received G-CSF support, there was a decrease in all-cause mortality, with a relative risk reduction of 0.897 and an absolute risk reduction of 3.4%; the average follow-up was 5 years.
The chair of the NCCN's Myeloid Growth Factors Panel suggested that this risk and benefit of prophylaxis is acceptable and the favored usage.
"The leukemia risk is very small compared with the overall mortality benefit," Jeffrey Crawford, MD, from the Duke Cancer Institute in Durham, North Carolina, explained to the meeting audience.
Dr. Crawford told Medscape Medical News that the risk for leukemia in patients receiving G-CSF support was confounded by the fact that there was no dose reduction due to febrile neutropenia complications in such patients' chemotherapy; in other words, the growth factor "enabled" a full dose of chemotherapy. Still, "the leukemia increase is slight but real," he said.
In another change, the guideline now recommends that primary prophylaxis with G-CSF "be considered" in patients receiving cabazitaxel, the new chemotherapy for metastatic prostate cancer. "The published results for cabazitaxel have an 8% rate of febrile neutropenia and neutropenia deaths reported," reads the guideline.
Take This Home
Dr. Crawford said that his presentation had a number of take-home messages.
First, "febrile neutropenia is still the major cause of mortality from chemotherapy," he said. Nearly one tenth (9.5%) of all adult cancer patients who are hospitalized for febrile neutropenia due to chemotherapy will die of the complication. The percentage decreases if no comorbidities are present (2.6%), and increases if 1 (10.3%) or more comorbidities (≥24.1%) are present.
The risk for febrile neutropenia increases with the duration of severe neutropenia, said Dr. Crawford, who added that the risk increases by about 10% with each day of neutropenia.
Second, Dr. Crawford wanted audience members to know that the highest risk for febrile neutropenia occurs in the first cycle of chemotherapy. "Unlike other toxicities," he said, febrile neutropenia does not typically occur because of a cumulative effect of chemotherapy.
Dr. Crawford showed a slide detailing, by cancer type, the proportion of febrile neutropenia occurring in the first cycle. Chemotherapy for colorectal cancer had the highest proportion (80%), followed by small-cell lung cancer (71%) and breast cancer (58%). For most of the cancers highlighted, the percentage was in the mid-50s.
Managing Neutropenia
The management of chemotherapy-induced neutropenia is a strategy of either prevention or treatment; the latter is complicated by the fact that myeloid growth factors are of "limited benefit" when used after the problem develops.
Prevention can be achieved by chemotherapy dose reduction or delay, which is not desirable. "I always feel guilty about dose reducing," said Suzanne Cole, MD, a medical oncologist from Charlestown, West Virginia, who attended the NCCN meeting.
Prevention can also be attempted with antibiotics, which have been shown to reduce mortality in neutropenia patients. However, Dr. Crawford cautioned against the use of antibiotics for a number of reasons, including their causing antibiotic resistance. "The NCCN does not recommend routine use of prophylactic antibiotics," he said, adding that an estimated 20 patients must be treated to prevent 1 case of febrile neutropenia.
The best method of preventing neutropenia is with myeloid growth factors, suggested Dr. Crawford, including G-CSF (filgrastim, lenograstim), granulocyte-macrophage CSF (sargramostim, molgramostim), and pegfilgrastim (the longer-acting form of filgrastim).
The timing of the administration of prophylactic myeloid growth factors is key, he said. The guideline indicates that the prophylaxis should be administered within 24 to 72 hours of the end of a chemotherapy cycle.
Who should get prophylactic myeloid growth factor is clear and unclear, said Dr. Crawford. The NCCN recommends all patients at high risk — that is, with a greater than 20% chance of developing febrile neutropenia — receive the treatment.
The factors that influence risk are the type of cancer and chemotherapy, individual patient risk factors, and treatment intent. The NCCN guideline lists the disease settings and chemotherapy regimens with a high risk for febrile neutropenia, such as docetaxel and trastuzumab for breast cancer. However, although the list is long, it is not comprehensive, according to the NCCN.
"You don't need to think about it," said Dr. Crawford about using growth factors in high-risk patients. He also said that prophylactic CSF are warranted in the first and all subsequent cycles of chemotherapy.
More controversial is the use of growth factors in intermediate-risk patients. The guideline has a long list of intermediate-risk disease settings and chemotherapy regimens.
Individual risk factors such as age and performance status come into play more with intermediate-risk chemotherapy regimens, said Dr. Crawford.
One audience member at the meeting brought up the fact that the cost of pegfilgrastim discourages its use in many patients. However, after Dr. Crawford's presentation, Dr. Cole told Medscape Medical News that she feels differently about the use and cost of prophylactic myeloid growth factors.
"Using [pegfilgrastim] was not ingrained in me the way it should be," she said.
She explained that pegfilgrastim costs about $2200 a treatment at her institution. Febrile neutropenia, in contrast, usually results in at least a 3-day admission. The cost of a day in the hospital is about $2000. Thus, the economics favor the use in some cases, she suggested.
"This was the most valuable and interesting talk at the meeting so far," said Dr. Cole.
Dr. Crawford reports being a consultant to Amgen, GlaxoSmithKline, Johnson & Johnson, Medtronic, Aggenix AG, Chugai Pharmaceuticals, and Ono Pharmaceuticals; and receiving research support from Celgene, Facet Biotech, and Hoffman LaRoche.
National Comprehensive Cancer Network (NCCN) 16th Annual Conference. Presented March 12, 2011.
There is a "slight excess risk" of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) in patients treated with colony-stimulating factors (CSF) for the prevention of febrile neutropenia associated with chemotherapy, the footnote says.
The content of the footnote is derived from a systematic review of randomized clinical trials of cancer patients receiving chemotherapy with or without primary G (granulocyte)-CSF support. With G-CSF use, there was a nearly 2-fold relative risk increase (1.92) and an absolute risk increase of 0.41% for AML/MDS; the average length of follow-up was 2 years.
On the plus side of the systematic review's findings, there was a reduction in all-cause mortality in patients treated with G-CSF. Specifically, in patients who received G-CSF support, there was a decrease in all-cause mortality, with a relative risk reduction of 0.897 and an absolute risk reduction of 3.4%; the average follow-up was 5 years.
The chair of the NCCN's Myeloid Growth Factors Panel suggested that this risk and benefit of prophylaxis is acceptable and the favored usage.
"The leukemia risk is very small compared with the overall mortality benefit," Jeffrey Crawford, MD, from the Duke Cancer Institute in Durham, North Carolina, explained to the meeting audience.
Dr. Crawford told Medscape Medical News that the risk for leukemia in patients receiving G-CSF support was confounded by the fact that there was no dose reduction due to febrile neutropenia complications in such patients' chemotherapy; in other words, the growth factor "enabled" a full dose of chemotherapy. Still, "the leukemia increase is slight but real," he said.
In another change, the guideline now recommends that primary prophylaxis with G-CSF "be considered" in patients receiving cabazitaxel, the new chemotherapy for metastatic prostate cancer. "The published results for cabazitaxel have an 8% rate of febrile neutropenia and neutropenia deaths reported," reads the guideline.
Take This Home
Dr. Crawford said that his presentation had a number of take-home messages.
First, "febrile neutropenia is still the major cause of mortality from chemotherapy," he said. Nearly one tenth (9.5%) of all adult cancer patients who are hospitalized for febrile neutropenia due to chemotherapy will die of the complication. The percentage decreases if no comorbidities are present (2.6%), and increases if 1 (10.3%) or more comorbidities (≥24.1%) are present.
The risk for febrile neutropenia increases with the duration of severe neutropenia, said Dr. Crawford, who added that the risk increases by about 10% with each day of neutropenia.
Second, Dr. Crawford wanted audience members to know that the highest risk for febrile neutropenia occurs in the first cycle of chemotherapy. "Unlike other toxicities," he said, febrile neutropenia does not typically occur because of a cumulative effect of chemotherapy.
Dr. Crawford showed a slide detailing, by cancer type, the proportion of febrile neutropenia occurring in the first cycle. Chemotherapy for colorectal cancer had the highest proportion (80%), followed by small-cell lung cancer (71%) and breast cancer (58%). For most of the cancers highlighted, the percentage was in the mid-50s.
Managing Neutropenia
The management of chemotherapy-induced neutropenia is a strategy of either prevention or treatment; the latter is complicated by the fact that myeloid growth factors are of "limited benefit" when used after the problem develops.
Prevention can be achieved by chemotherapy dose reduction or delay, which is not desirable. "I always feel guilty about dose reducing," said Suzanne Cole, MD, a medical oncologist from Charlestown, West Virginia, who attended the NCCN meeting.
Prevention can also be attempted with antibiotics, which have been shown to reduce mortality in neutropenia patients. However, Dr. Crawford cautioned against the use of antibiotics for a number of reasons, including their causing antibiotic resistance. "The NCCN does not recommend routine use of prophylactic antibiotics," he said, adding that an estimated 20 patients must be treated to prevent 1 case of febrile neutropenia.
The best method of preventing neutropenia is with myeloid growth factors, suggested Dr. Crawford, including G-CSF (filgrastim, lenograstim), granulocyte-macrophage CSF (sargramostim, molgramostim), and pegfilgrastim (the longer-acting form of filgrastim).
The timing of the administration of prophylactic myeloid growth factors is key, he said. The guideline indicates that the prophylaxis should be administered within 24 to 72 hours of the end of a chemotherapy cycle.
Who should get prophylactic myeloid growth factor is clear and unclear, said Dr. Crawford. The NCCN recommends all patients at high risk — that is, with a greater than 20% chance of developing febrile neutropenia — receive the treatment.
The factors that influence risk are the type of cancer and chemotherapy, individual patient risk factors, and treatment intent. The NCCN guideline lists the disease settings and chemotherapy regimens with a high risk for febrile neutropenia, such as docetaxel and trastuzumab for breast cancer. However, although the list is long, it is not comprehensive, according to the NCCN.
"You don't need to think about it," said Dr. Crawford about using growth factors in high-risk patients. He also said that prophylactic CSF are warranted in the first and all subsequent cycles of chemotherapy.
More controversial is the use of growth factors in intermediate-risk patients. The guideline has a long list of intermediate-risk disease settings and chemotherapy regimens.
Individual risk factors such as age and performance status come into play more with intermediate-risk chemotherapy regimens, said Dr. Crawford.
One audience member at the meeting brought up the fact that the cost of pegfilgrastim discourages its use in many patients. However, after Dr. Crawford's presentation, Dr. Cole told Medscape Medical News that she feels differently about the use and cost of prophylactic myeloid growth factors.
"Using [pegfilgrastim] was not ingrained in me the way it should be," she said.
She explained that pegfilgrastim costs about $2200 a treatment at her institution. Febrile neutropenia, in contrast, usually results in at least a 3-day admission. The cost of a day in the hospital is about $2000. Thus, the economics favor the use in some cases, she suggested.
"This was the most valuable and interesting talk at the meeting so far," said Dr. Cole.
Dr. Crawford reports being a consultant to Amgen, GlaxoSmithKline, Johnson & Johnson, Medtronic, Aggenix AG, Chugai Pharmaceuticals, and Ono Pharmaceuticals; and receiving research support from Celgene, Facet Biotech, and Hoffman LaRoche.
National Comprehensive Cancer Network (NCCN) 16th Annual Conference. Presented March 12, 2011.
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