Use of G-CSF Optimizes CHOP Dosing and Improves Outcome in Elderly Patients With Large-Cell Lymphoma

NEW YORK—The addition of G-CSF (Neupogen) to standard CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) may improve disease outcome in elderly patients with large-cell lymphoma by allowing optimal drug dosing, Gerard Donnelly, MD, said at the Fortieth Annual Meeting of the American Society of Hematology (ASH).

Although CHOP is the gold standard for large-cell lymphoma, elderly patients may not get the full benefits of the regimen because of dose-limiting hematologic toxicity.

Dr. Donnelly, a fellow in hematology-oncology at Memorial Sloan-Kettering Cancer Center, said that in elderly patients, CHOP doses are often reduced by 50% to 75% due to patient frailty or other complications. “With G-CSF, we can treat the disease more aggressively,” Dr. Donnelly commented.

The researchers worked with Dr. Carol Portlock at Memorial Sloan-Kettering Cancer Center to retrospectively identify 51 previously untreated large-cell lymphoma patients over 60 years of age who received CHOP plus G-CSF at Sloan-Kettering from 1991 to 1995.

Patients were ineligible for other protocols for a number of reasons, including age (20 patients), another malignancy (5 patients), and other co-morbidities (12 patients). All patients were negative for HIV infection.

The median age was 72 years (range, 61 to 85). Using the age-adjusted International Prognostic Index (IPI), 27 patients were judged low or low-intermediate risk; 13, high-intermediate risk; and 11, high risk.

G-CSF Dosing

Patients received CHOP at 3-week intervals (mean, 5.9 cycles per patient). The G-CSF dose was 5 µg/kg/day for 5 to 8 days. It was given after each CHOP cycle in 51% of patients and for the majority of cycles in 86% of patients.

There were a total of 50 treatment delays occurring in 28 patients, and 10 of these patients had two or more delays. There were no treatment delays in 23 patients.

The actual cyclophosphamide dose was 695.2 mg/m² (93% of the optimal dose). The patients received 47.8 mg/m² of doxorubicin (96% of the optimal dose).

The researchers analyzed patient outcomes according to the age-adjusted IPI, and then compared these data with the 5-year results from the IPI study of large-cell lymphoma patients (N Engl J Med 329:987-994, 1993).

Responses in Elderly

They found that their elderly patients who received G-CSF plus CHOP had complete response rates, 5-year actuarial relapse-free survival, and overall survival superior to those of the IPI patients over the age of 60 and comparable to those of the IPI patients under the age of 60.

Dr. Donnelly said that by adding G-CSF, the standard CHOP treatment could be given nearly at its optimal dosing level in these elderly patients with large-cell lymphoma.

“There are some limitations to the study, and there needs to be further investigation,” he commented, “especially in a prospective analysis.”