The CHOP (cyclophosphamide, doxorubicin(Drug information on doxorubicin), Oncovin, and prednisone(Drug information on prednisone)) regimen has been the standard approach to patients with advanced-stage intermediate-grade non-Hodgkins lymphoma (NHL) for more than 20 years.A randomized comparison between CHOP, m-BACOD (methotrexate, bleomycin, Adriamycin, cyclophosphamide(Drug information on cyclophosphamide), Oncovin, and dexamethasone(Drug information on dexamethasone)),
ProMACE/CytaBOM (prednisone, methotrexate(Drug information on methotrexate), Adriamycin, cyclophosphamide, etoposide, cytarabine(Drug information on cytarabine), bleomycin(Drug information on bleomycin), and Oncovin), and MACOP-B (methotrexate, Adriamycin, cyclophosphamide, Oncovin, prednisone, and bleomycin) failed to show any advantage for the more intensive regimens. Moreover, CHOP was less expensive and had a lower mortality than the other programs (Fisher et al: N Engl J Med 328:1002-1006, 1993). Nevertheless, only 30% to 40% of patients are cured with this regimen.
Using the International Prognostic Index (IPI), Shipp et al determined that the likelihood of cure correlates with a number of clinical factors: age, stage, lactic dehydrogenase (LDH) level, performance status, and number of extranodal sites (Shipp et al: N Engl J Med 329:987-994, 1993). They found that patients ³ 60 years of age have a particularly poor outlook with aggressive chemotherapy regimens, such as CHOP. Their poor outcome may be related, in part, to a lower delivered dose of chemotherapy.
Zinzani et al reported the favorable experience of the Italian Cooperative Study Group (abstract #2567) using VNCOP-B (vincristine, Novantrone, cyclophosphamide, etoposide(Drug information on etoposide), bleomycin, and prednisone) as initial treatment in elderly patients with high-grade NHL.
Single-arm studies of chemotherapy regimens, no matter how promising, should be interpreted with caution, as subsequent randomized trials have uniformly failed to confirm these leads. The practice of developing regimens based on minor modifications of dose and schedule of conventional agents should be discouraged. More innovative strategies are obviously needed.
Bruce D. Cheson, MD