Failure of intensive chemotherapy in poor prognosis non-Hodgkin's lymphoma

In an attempt to improve response and survival rates in patients with non-Hodgkin's lymphoma, a relatively intense six drug regimen MATCOP was developed comprising four-weekly cycles of methotrexate (100 mg/m2, IV, day 8), Adriamycin (30 mg/m2, IV, days 1,2), teniposide (75 mg/m2, IV, day 1), cyclophosphamide (300 mg/m2, po, days one to five), Oncovin (1.4 mg/m2, IV: maximum 2 mg, days 8, 15) and prednisolone (100 mg, po, days one to five). A randomised trial was conducted comparing MATCOP with the standard CHOP regimen, comprising three-weekly cycles of cyclophosphamide (750 mg/m2, IV, day 1), Adriamycin (50 mg/m2, IV, day 1), Oncovin (1.4 mg/m2 IV: maximum 2 mg, day 1) and prednisolone (100 mg, po, days two to six). Eighty patients with large cell lymphoma, diffuse mixed small cleaved and large cell lymphoma or diffuse small cleaved cell lymphoma were randomised, 47 to MATCOP and 33 to CHOP. MATCOP patients experienced increased granulocytopenia, thrombocytopenia (p less than 0.0001), mucositis (p = 0.002) and infections (p = 0.01) compared to CHOP patients. Complete response rates were similar: 66% for MATCOP patients and 61% for CHOP patients. There were no apparent differences in the time to relapse for patients achieving CR, the time to treatment failure or the overall survival time. Thus despite an increase in toxicity, the more intense regimen MATCOP failed to confer any therapeutic benefit compared with the standard CHOP regimen. Survival was not influenced but toxicity was increased by dose intensification.