Are Older Lymphoma and Breast Cancer Patients Undertreated?

According to data presented at the American Society ofHematology (ASH) meeting and the San Antonio Breast Cancer Symposium, elderlycancer patients may be up to two times as likely as younger patients to receivechemotherapy doses below the levels demonstrated in previously published studiesto provide the best chances for survival. Authors from both studies suggest thatsuboptimal chemotherapy dosing may help explain poorer response and survivaloutcomes in the elderly, and that neutropenia is a major contributor to reducedchemotherapy 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-gradenon-Hodgkin’s lymphoma to analyze the relationship between age, side effects,and chemotherapy dose reductions. The second data analysis, presented at the SanAntonio Breast Cancer Symposium, reviewed the medical charts of 20,799 breastcancer patients who received adjuvant chemotherapy to investigate physicians’practice patterns and factors that contribute to chemotherapy dose variations.

"When elderly cancer patients receive full chemotherapydoses, their survival rates are as good as younger patients. These data suggestthat doctors are not dosing older patients as optimally as they are youngerpatients," said Gary Lyman, MD, MPH, Albany Medical Center. "If weaggressively address the factors, such as neutropenia, that are causing elderlypatients to receive suboptimal chemotherapy, we may have a positive impact ontheir long-term survival."

Elderly With Non-Hodgkin’sLymphoma Underdosed

Researchers in the Lymphoma Service of Memorial Sloan-KetteringCancer Center looked at the medical records of 1,761 intermediate-gradenon-Hodgkin’s lymphoma patients (49% were ³ 65 years old) from 226 communityoncology practices across the United States to determine the relationshipbetween age, various clinical parameters, and chemotherapy regimenmodifications. In the study, 1,514 patients (86%) were given CHOP(cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin],prednisone), which is the standard treatment, 141 patients (8%) received CNOP(cyclophosphamide, mitoxantrone [Novantrone], Oncovin, prednisone), and 106patients (6%) received CVP (cyclophosphamide, vincristine, prednisone).

The data reviewed demonstrated that older patients were morefrequently prescribed the less aggressive regimens (CNOP and CVP) than CHOP (21%vs 7%, P < .001). Also, regardless of the regimen, older patientswere 1.8 times more likely to begin therapy at a lower dose intensity, and twotimes more likely to experience dose reductions or delays than younger patients.Overall, 43% of elderly patients and 23% of younger patients received suboptimaldosing.

The study’s authors note that research with elderly patientshas consistently shown that complete response to treatment is significantlyhigher in groups who receive full chemotherapy doses than in those who receivereduced doses. The authors further point out that while the myelotoxicity ofCHOP and CHOP-like regimens may limit the ability to deliver the standardchemotherapy dose, dose delays or reductions may be decreased by usinggranulocyte colony-stimulating factor (G-CSF [Neupogen]), which stimulates theproduction of neutrophils.

"The variation in treatment between older and youngerpatients we found is significant because there seems to be a relationshipbetween dose, complete response rates, and survival," said Andrew Zelenetz,MD, chief of the lymphoma service at Memorial Sloan-Kettering. "Theanalysis is also interesting since there is a growing opinion that proactive useof G-CSF should be standard practice among high-risk patients over 65 years whoare 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 withbreast cancer from 1,243 oncology practices nationwide to determine practicepatterns with respect to relative chemotherapy dose intensity over a course ofconventional adjuvant breast cancer chemotherapy. The data review also looked atthe frequency of treatment delays, chemotherapy dose reductions, and episodes offebrile neutropenia.

The data showed that more than 25% of all patients experiencedreductions in chemotherapy dose, and 43% had a treatment delay. Patients aged 65years 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 thevariations in dosing, including side effects, type of regimen, and diagnosis. Apatient’s diagnosis also had an impact on dose variations. Node-negativepatients were more likely (45.9%) to receive a lower-than-standard chemotherapydose, compared to patients with one to four positive nodes. The regimen usedmost commonly in the study was CMF (cyclophosphamide, methotrexate, fluorouracil[5-FU]), followed by CAF (cyclophosphamide, doxorubicin [Adriamycin], 5-FU) andAC (Adriamycin, cyclophosphamide), with the most common reductions or delaysoccurring with CMF (22.2%) and CAF (24.4%).

The researchers evaluating these data are continuing theiranalysis with the goal of developing a risk model to help physicians manage andpredict neutropenia. The model is expected to be completed in spring 2001.