Interferon Plus Anthracycline-Based Regimen Effective in Intermediate-Grade NHL

CHICAGO—A new regimen that includes an anthracycline plus interferon-alfa-2b (Intron A) as induction chemotherapy of patients with low- or intermediate-grade non-Hodgkin’s lymphoma (NHL) appears to be as effective as CHOP, Sari Enschede, MD, of Rush Presbyterian-St. Luke Medical Center, said at an ASH poster session.

“For intermediate-grade NHL, this treatment is at least as effective as standard CHOP and may be more effective,” she said.(CHOP: cyclophosphamide, doxorubicin, vincristine, prednisone.)

The 68 patients in the phase II trial conducted at the Rush Cancer Institute were treated between January 1993 and September 1996. They received cyclophosphamide (750 mg/m²), mitoxantrone (Novantrone) (12 mg/m²), and teniposide (Vumon) (60 mg/m²) on day 1; prednisone (100 mg/d) on days 1 to 5; vincristine (1.4 mg/m²) and bleomycin (Blenoxane) (10 units/m²) on day 15; and interferon (5 × 10⁶ units/m2) on days 22 to 26 of a 28-day cycle (see Table).

The rationale for adding interferon is based on studies showing that administration of agents that slow tumor proliferation between courses of cytotoxic therapy can overcome regrowth resistance, Dr. Enschede said.

The median age of the patients was 52 years. Thirty-six had low-grade and 32 had intermediate-grade NHL. Most had stage III-IV NHL (81%), and the remaining 19% had stage I-II disease. The median IPI (International Prognostic Index) was 2.

Response Rates

Of the low-grade NHL patients, 67% had a complete response and 33% a partial response. Of those with intermediate-grade NHL, 59% had a complete response and 22% a partial response.

Overall and event-free survival was the same in the low-grade patients (about 65% at 4.2 years). For the intermediate-grade patients, overall survival was 81% and event-free survival was 56% at 4.3 years. Patients with advanced stage (III-IV) intermediate-grade disease were assessed independently and found to have an overall survival and event-free survival of 89% and 63%, respectively, at 4.3 years.

Compared with the results of the Intergroup trial by SWOG and ECOG that evaluated standard CHOP therapy (N Engl J Med, 1993), the intermediate-grade NHL patients on the new regimen seemed to fare better, she said.

The Intergroup trial patients with advanced intermediate-grade disease had an overall survival of 54% at 3 years and 30% at 12 years. Disease-free survival was 41% at 3 years.

Leukopenia was the main severe toxicity, and “this was related to the chemotherapy regimen on days 1 to 15, but not to the interferon,” Dr. Enschede said in an interview. However, severe infection was rare. There were no severe (grade 4) hematologic, flu-like, GI, and infectious toxicities from interferon during days 22 to 28 of the cycles.

She commented that although longer follow-up is needed for the low-grade NHL patients, the reseachers feel that the preliminary results show better efficacy in intermediate-grade disease. “We are still enrolling patients with both low-grade and intermediate-grade lymphomas,” she said.