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Patterns of Chemotherapy Administration in Patients With Intermediate-Grade Non-Hodgkin’s Lymphoma

Patterns of Chemotherapy Administration in Patients With Intermediate-Grade Non-Hodgkin’s Lymphoma

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 (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 HCl, vincristine [Oncovin], 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.[1] That article recommends dose reductions of at least 20% for
doxorubicin and 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.[10]

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.[11] 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.[12] 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

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