- © 2001 by American Society of Clinical Oncology
Patients Aged ≥ 70 Are at High Risk for Neutropenic Infection and Should Receive Hemopoietic Growth Factors When Treated With Moderately Toxic Chemotherapy
To the Editor:
We thank and congratulate your panel for a very thorough review of the utilization of hemopoietic growth factors and for the formulation of very practical guidelines.1 For completeness, we suggest that patients aged 70 and older who are receiving moderately toxic chemotherapy (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone [CHOP] or CHOP-like) be specifically mentioned as a special high-risk group recommended to receive primary prophylactic treatment with growth factors starting up front with the first course of chemotherapy. Our suggestion is based on the following considerations and data.
First, approximately 40% of all neoplasms occur in persons aged 70 and older, and this percentage is likely to increase with the simultaneous expansion of the older population and shrinkage of the younger population.2 Within the next 20 years, persons aged 70 and older will represent the majority of patients receiving chemotherapy.
Second, in nine studies of older individuals with large-cell non-Hodgkin’s lymphoma3-12 ( Tables 1 and 2⇓), the risk of life-threatening neutropenia was higher than 40% in all studies. The risk of neutropenic infections varied between 21% and 47%, and the risk of infectious death varied between 5% and 30%. The majority of deaths and serious infections occurred in the first course of chemotherapy, before secondary prophylaxis with growth factors could even be considered. In the study of Gomez et al,6 there were 51 deaths (20%) among 260 patients receiving chemotherapy; 36 deaths occurred during the first two courses of chemotherapy, and 63% of these were after the first course. Generally the seriousness of neutropenic infections is increased, and so is the duration of hospitalization in older individuals, involving a substantially increased cost per infection.13 Furthermore, hospitalization of older individuals is associated with increased risk of functional dependence that may increase the cost of treatment due to expensive home care and rehabilitation.14
Incidence of Life-Threatening Neutropenia, Neutropenic Infection, and Death in Older Individuals With Large-Cell Non-Hodgkin’s Lymphomas Treated With CHOP-Like Regimens
Third, in at least four studies, hemopoietic growth factors reduced the risk of neutropenia and neutropenic infection by 32% to 83% in older patients with large-cell non-Hodgkin’s lymphomas ( Table 2).4,7,11,15 In addition, in virtually all studies of acute myelogenous leukemia, the use of growth factors was associated with shortened hospitalization in older individuals, and in two studies it was associated with improved survival.16-18
Efficacy of Hemopoietic Growth Factors in Older Patients With Large-Cell Non-Hodgkin’s Lymphomas
Fourth, a number of studies showed that dose reduction or elimination of the anthracycline in the treatment of older patients with non-Hodgkin’s lymphoma is associated with a poorer outcome.8,19,20
Fifth, and finally, the National Comprehensive Cancer Network advisory panel for the guidelines for the management of older individuals has unanimously recommended that hemopoietic growth factors be used routinely in persons aged 70 and older who are receiving moderately toxic chemotherapy.21
References
Response
In Reply:
We appreciate the favorable response of Drs Balducci and Lyman to our article updating the American Society of Clinical Oncology’s (ASCO’s) hematopoietic growth factor guidelines. In addition, we fully concur with their suggestion that, in settings in which the risk of febrile neutropenia after chemotherapy exceeds 40%, primary prophylaxis with hematopoietic growth factors is now the standard of care. That setting clearly applies in those studies cited by Balducci and Lyman, which focussed on patients over age 70 receiving moderate-dose chemotherapy, primarily CHOP or CHOP-like regimens for non-Hodgkin’s lymphoma.
As noted in the 2000 update of the guidelines, such patients may fall under the category of “special circumstances” and would therefore be considered for primary prophylaxis with any chemotherapy regimen likely to cause myelosuppression, especially when administered with curative intent.1 This category of “special circumstances” is not meant to be restrictive, but rather to encourage clinical judgment by the treating oncologist who has the experience to recognize those individuals and chemotherapy regimens most likely to lead to life-threatening febrile neutropenia among his or her patient population.
Balducci and Lyman emphasize that the proportion of patients over age 70 is steadily increasing, and that the incidence of some tumors, such as non-Hodgkin’s lymphoma, is increasing as well. Coupled with the development of novel myelosuppressive agents and the tendency to diagnose and treat more such patients with curative intent than in past decades, it is evident that a steadily growing elderly population of cancer patients is at risk for febrile neutropenia and therefore would be excellent candidates for primary prophylaxis with hematopoietic growth factors, as recommended in the 2000 ASCO guidelines.
