EORTC Cancer in the Elderly: Task Force Guidelines for the Use of Colony-Stimulating Factors in Elderly Patients with Cancer

Abstract & Commentary

Synopsis: This study outlines recent EORTC cancer guidelines in chemotherapy in the elderly.

Source: Repetto L, et al. Eur J Cancer. 2003;39: 2264-2272.

Advancing age is not, in itself, a contraindication to cancer chemotherapy, but many clinicians are reluctant to use chemotherapy in elderly patients. While myelosuppression is a common adverse consequence of the administration of many standard-dose chemotherapy regimens in both young and elderly patients with cancer, increasing age is associated with increasing hematological toxicity and is a significant independent predictor of the development of febrile neutropenia.1 This increased risk of myelosuppression may contribute to a reluctance to administer chemotherapy in the elderly patient population. Chemotherapy dose reduction or delay is often used to manage chemotherapy-induced neutropenia. This may have a negative effect on outcome. An alternative strategy is to use hematopoietic growth factors. It has been documented that elderly patients respond well to administered granulocyte-colony stimulating factor (G-CSF).2 G-CSF has been recommended to provide cost-effective support of the first and subsequent cycles of chemotherapy in patients who have an expected incidence of febrile neutropenia—40% of whom are at high risk of infection complications or for the avoidance of further episodes of febrile neutropenia following an initial occurrence.

The National Cancer Center Network (NCCN) has recommended that routine primary prophylactic growth factors should be used in patients aged 70 years who are receiving moderately myelotoxic chemotherapy of a comparable dose intensity to 21-day cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

The American Society of Clinical Oncology (ASCO) Committee on Guidelines for the use of Hematopoietic Growth Factors has concurred with the NCCN recommendation.3,4 The European Organization for Research and Treatment of Cancer (EORTC) has reviewed the existing published data and has derived evidence-based conclusions on the value of CSF administration in elderly patients.

Comment by Stuart M. Lichtman, MD, FACP

The task force did electronic searches using the MEDLINE database from 1992 to March 2002 using search terms relating to different tumor types, G-CSF or GM-CSF, with a median age of 60 years. Evidence levels used by ASCO were applied to the results of the literature search to classify the data. Seven tumor types were investigated: breast cancer, colorectal cancer, non-Hodgkin’s lymphoma, non-small-cell lung cancer, ovarian cancer, small-cell lung cancer, and urothelial cancer. A total of 330 references were identified, but greater than 90% were excluded during review. The major reasons for exclusions were median age younger than 60 years and a lack of direct comparison of growth factor vs non growth factor. In total, 30 papers provided evidence considered relevant by the EORTC panel. There were very few data for patients older than 70 years of age.

A metaanalysis of 8 randomized, controlled trials, not restricted to an elderly population, has confirmed the value of G-CSF in reducing the risk of febrile neutropenia, documented infection, and the need for dose-intensity reduction.5 The EORTC literature review highlighted a lack of well-designed clinical trials to assess the use of hematopoietic growth factors in elderly patients with cancer. The data retrieved allowed consideration of the use of prophylactic G-CSF in elderly patients with urothelial cancer, non-Hodgkin’s lymphoma and small-cell lung cancer. The available evidence endorses the use of prophylactic G-CSF 5 g/kg/d to support the administration of planned doses of chemotherapy on schedule in standard chemotherapy settings and reduce the incidence of chemotherapy induced neutropenia and its sequelae. Lack of available trial data does not allow similar conclusions to be drawn for the other malignancies, but it is likely that similar benefits would accrue from the use of prophylactic G-CSF. There is no evidence that the delivery of standard-dose chemotherapy on schedule improves outcome measures. There is evidence that dose-intensification can improve outcome in elderly patients with urothelial cancer, small-cell lung cancer, and non-Hodgkin’s lymphoma. Their research provided no data to support the use of prophylactic G-CSF to reduce the incidence of toxic death. There is no evidence that prophylactic G-CSF improves efficacy outcome measures, including response rates, progression-free survival, or overall survival in standard dose regimens.

The task force recommended the use of prophylactic G-CSF to support the administration of planned doses of chemotherapy on schedule and reduce the incidence of chemotherapy-induced neutropenia, febrile neutropenia, and infections in elderly patients receiving myelotoxic chemotherapy. Since febrile neutropenic events are more likely to occur during the first and second cycles of chemotherapy, prophylactic measures should be considered early in the course of treatment. They also propose primary prophylactic use of G-CSF for all elderly patients receiving curative myelotoxic chemotherapy (CHOP or CHOP-like) and a risk-adapted strategy with primary prophylactic G-CSF administration in high-risk patients, as suggested by the ASCO guidelines for all patients. Further prospective trials are urgently needed.

Dr. Lichtman is Associate Professor of Medicine NYU School of Medicine Division of Oncology; Don Monti Division of Medical Oncology North Shore University Hospital, Manhasset, NY.

References

1. Repetto L, Balducci L. Lancet Oncol. 2002;3:289-297.

2. Chatta GS, et al. J Am Geriatr Soc. 1994;42:77-81.

3. Balducci L, Yates J. Oncology (Huntingt). 2000;14: 221-227.

4. Balducci L, Lyman GH. J Clin Oncol. 2001;19: 1583-1585.

5. Lyman GH, et al. Am J Med. 2002;112:406-411.