According to data presented at the American Society of Hematology (ASH) meeting and the San Antonio Breast Cancer Symposium, elderly cancer patients may be up to two times as likely as younger patients to receive chemotherapy doses below the levels demonstrated in previously published studies to provide the best chances for survival. Authors from both studies suggest that suboptimal chemotherapy dosing may help explain poorer response and survival outcomes in the elderly, and that neutropenia is a major contributor to reduced chemotherapy doses in the elderly.
The first set of data, presented at December’s ASH meeting, looked at the medical records of 1,761 patients with intermediate-grade non-Hodgkin’s lymphoma to analyze the relationship between age, side effects, and chemotherapy dose reductions. The second data analysis, presented at the San Antonio Breast Cancer Symposium, reviewed the medical charts of 20,799 breast cancer patients who received adjuvant chemotherapy to investigate physicians’ practice patterns and factors that contribute to chemotherapy dose variations.
"When elderly cancer patients receive full chemotherapy doses, their survival rates are as good as younger patients. These data suggest that doctors are not dosing older patients as optimally as they are younger patients," said Gary Lyman, MD, MPH, Albany Medical Center. "If we aggressively address the factors, such as neutropenia, that are causing elderly patients to receive suboptimal chemotherapy, we may have a positive impact on their long-term survival."
Elderly With Non-Hodgkin’s Lymphoma Underdosed
Researchers in the Lymphoma Service of Memorial Sloan-Kettering Cancer Center looked at the medical records of 1,761 intermediate-grade non-Hodgkin’s lymphoma patients (49% were ³ 65 years old) from 226 community oncology practices across the United States to determine the relationship between age, various clinical parameters, and chemotherapy regimen modifications. In the study, 1,514 patients (86%) were given CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin(Drug information on doxorubicin) HCl, vincristine [Oncovin], prednisone), which is the standard treatment, 141 patients (8%) received CNOP (cyclophosphamide, mitoxantrone(Drug information on mitoxantrone) [Novantrone], Oncovin, prednisone(Drug information on prednisone)), and 106 patients (6%) received CVP (cyclophosphamide, vincristine, prednisone).
The data reviewed demonstrated that older patients were more frequently prescribed the less aggressive regimens (CNOP and CVP) than CHOP (21% vs 7%, P < .001). Also, regardless of the regimen, older patients were 1.8 times more likely to begin therapy at a lower dose intensity, and two times more likely to experience dose reductions or delays than younger patients. Overall, 43% of elderly patients and 23% of younger patients received suboptimal dosing.
The study’s authors note that research with elderly patients has consistently shown that complete response to treatment is significantly higher in groups who receive full chemotherapy doses than in those who receive reduced doses. The authors further point out that while the myelotoxicity of CHOP and CHOP-like regimens may limit the ability to deliver the standard chemotherapy dose, dose delays or reductions may be decreased by using granulocyte colony-stimulating factor (G-CSF [Neupogen]), which stimulates the production of neutrophils.
"The variation in treatment between older and younger patients we found is significant because there seems to be a relationship between dose, complete response rates, and survival," said Andrew Zelenetz, MD, chief of the lymphoma service at Memorial Sloan-Kettering. "The analysis is also interesting since there is a growing opinion that proactive use of G-CSF should be standard practice among high-risk patients over 65 years who are expected to receive full-dose CHOP."
Contributors to Suboptimal Dosing
Researchers from Duke University, the University of Washington, and Albany Medical College reviewed the medical records of 20,799 patients with breast cancer from 1,243 oncology practices nationwide to determine practice patterns with respect to relative chemotherapy dose intensity over a course of conventional adjuvant breast cancer chemotherapy. The data review also looked at the frequency of treatment delays, chemotherapy dose reductions, and episodes of febrile neutropenia.
The data showed that more than 25% of all patients experienced reductions in chemotherapy dose, and 43% had a treatment delay. Patients aged 65 years and older had a greater number of dose reductions (31.1% vs 24.7%, P < .001) and treatment delays (50.4% vs 41.7%, P < .001).
The analysis revealed that several factors contributed to the variations in dosing, including side effects, type of regimen, and diagnosis. A patient’s diagnosis also had an impact on dose variations. Node-negative patients were more likely (45.9%) to receive a lower-than-standard chemotherapy dose, compared to patients with one to four positive nodes. The regimen used most commonly in the study was CMF (cyclophosphamide, methotrexate(Drug information on methotrexate), fluorouracil(Drug information on fluorouracil) [5-FU]), followed by CAF (cyclophosphamide, doxorubicin [Adriamycin], 5-FU) and AC (Adriamycin, cyclophosphamide(Drug information on cyclophosphamide)), with the most common reductions or delays occurring with CMF (22.2%) and CAF (24.4%).
The researchers evaluating these data are continuing their analysis with the goal of developing a risk model to help physicians manage and predict neutropenia. The model is expected to be completed in spring 2001.