Dr. Picozzi and colleagues have presented an analysis from the Oncology Practice Patterns Study that examined patterns of care for patients with intermediate-grade non-Hodgkin’s lymphoma. Patients in their study were treated off protocol in managed-care practices, by community oncologists or in the academic setting. More than 40% of patients received a chemotherapy regimen that did not contain an anthracycline or mitoxantrone(Drug information on mitoxantrone) (Novantrone), or chemotherapy doses that were significantly lower than optimal. The authors appear to have made every effort to validate information obtained from the data collection forms, and we can assume that their results reflect "real world" standards of practice. We are not told whether results differed for patients treated in academic vs private-practice settings, and it would be interesting to know if such differences exist.
As might be expected, more than 50% of chemotherapy dose delays and reductions for patients receiving CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin(Drug information on doxorubicin) HCl, vincristine [Oncovin], prednisone(Drug information on prednisone)) or CNOP (cyclophosphamide, mitoxantrone, vincristine, prednisone) were related to neutropenia. However, it is disturbing that the reasons for 10% of the dose delays and 21% of the dose reductions could not be identified in the medical record. There are no firm guidelines regarding dose modifications for CHOP chemotherapy, and it is not surprising that there are wide variations in how physicians alter chemotherapy dosage according to blood counts.
Considerations About Dose Reductions
The authors of this study reference the article by McKelvey et al from the Southwest Oncology Group (SWOG) as the standard for CHOP administration. That article recommends dose reductions of at least 20% for doxorubicin and cyclophosphamide(Drug information on cyclophosphamide) in patients whose white blood cell count falls below 1,500/mm³ or whose platelet count falls below 50,000/mm³ during the preceding cycle of therapy. Other articles detailing methods of CHOP chemotherapy administration simply refer to the original reports[2,3] or recommend different schedules for dose modifications.[4,5] Standard textbooks fail to present recommendations regarding chemotherapy dose reductions for neutropenic patients.[6-9] This lack of consensus on dose modifications is not surprising, however, in light of numerous variations in the CHOP regimen itself.
Dr. Picozzi and coauthors note that the main reason for initiating chemotherapy at reduced doses was advanced age. Elderly patients with aggressive non-Hodgkin’s lymphoma frequently have adverse prognostic factors at presentation. They may experience inferior outcomes because of increased toxicity from chemotherapy, higher relapse rates, or higher death rates from cardiovascular disease. Treatment-related deaths in elderly patients receiving CHOP chemotherapy may be associated with performance status, rather than chronologic age. Most experts would not recommend arbitrary dose reductions based on age alone. However, this analysis does not allow us to determine the precise reasons for initiating chemotherapy at a reduced dose, and it is possible that decisions to do so were correct for individual patients.
It is likely that concerns about doxorubicin-induced cardiotoxicity were also responsible for dose reductions in elderly patients and those with a history of cardiac disease. These characteristics are associated with a higher risk of cardiotoxicity. Nevertheless, it is unknown whether the risk of cardiac toxicity is greater than the increased risk of death from lymphoma in patients who receive attenuated doses of anthracylines because of asymptomatic cardiac disease or reductions in cardiac ejection fraction.
Growth Factors and Nonstandard Regimens