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Background and Methods In 1981 the Clinical Trials Group of the National Cancer Institute of Canada completed a pilot study in patients with advanced-stage non-Hodgkin's lymphoma with aggressive tumor histology. That study demonstrated the potential efficacy of escalating the dose of doxorubicin used in a regimen of bleomycin, doxorubicin, cyclophosphamide, vincristine, and prednisone (BACOP). In the present study, we compared standard BACOP (s-BACOP) with BACOP that included escalated doses of doxorubicin (esc-BACOP) in 238 patients 16 to 70 years old with previously untreated, advanced-stage intermediate- or high-grade non-Hodgkin's lymphoma. During the first 28-day cycle all patients received doxorubicin in a dose of 25 mg per square meter of body-surface area on days 1 and 8. Patients randomly assigned to receive s-BACOP subsequently received five identical cycles, whereas those assigned to receive esc-BACOP received 40 mg of doxorubicin per square meter on days 1 and 8 of five subsequent cycles if granulocytopenia (<1000 cells per cubic millimeter) had not developed during the first cycle.
Results The 119 patients assigned to the esc-BACOP regimen received doxorubicin at a significantly higher mean weekly dose intensity (13.5 vs. 10.4 mg per square meter per week, P<0.001) and mean total dose (296 vs. 231 mg per square meter, P<0.001). Because of granulocytopenia during the first cycle of therapy, only 56 of these patients (47 percent) received the escalated doses of doxorubicin. During a median follow-up of 65 months, there were no differences between the s-BACOP and esc-BACOP groups in response rate, overall survival, or survival without disease progression. When the patients who actually received the escalated doses of doxorubicin were compared with the patients in the s-BACOP group in whom neutropenia did not develop during the first treatment cycle, no difference between their outcomes was observed. Toxicity was greater in the esc-BACOP group.
Conclusions In patients with advanced-stage intermediate- or high-grade non-Hodgkin's lymphoma, escalating the dose of doxorubicin in the BACOP regimen increases toxicity but does not improve the rate of response or survival.
Source Information
From the Hamilton Civic Hospitals and McMaster University, Hamilton, Ont. (R.M.M.); Princess Margaret Hospital and University of Toronto, Toronto (I.C.Q., M.K.G.); Nova Scotia Cancer Treatment and Research Foundation and Dalhousie University, Halifax, N.S. (J.R.S.); Ottawa Regional Cancer Centre (M.C.C.) and Ottawa Civic Hospital (B.F.B.), University of Ottawa, Ottawa, Ont.; London Regional Cancer Centre and University of Western Ontario, London, Ont. (V.H.C.B.); University of Manitoba and Manitoba Cancer Treatment and Research Foundation, Winnipeg, Man. (B.H.W.); National Cancer Institute of Canada Clinical Trials Group (A.M.S.) and Queen's University (L.E.S., B.Z.), Kingston, Ont.; and the Gildred Cancer Center-University of California, San Diego (W.M.H.). Conducted by the Clinical Trials Group (Joseph L. Pater, M.D., chairman) of the National Cancer Institute of Canada; participating investigators are listed in the Appendix.
Address reprint requests to Dr. Meyer at the McMaster Medical Unit, Henderson General Hospital, 711 Concession St., Hamilton, ON L8V 1C3, Canada.
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