Patients with advanced Hodgkin’s disease-Ann Arbor stage IIB to IV-were randomized to treatment with either four
Patients with advanced Hodgkins diseaseAnn Arbor stage IIB to IVwere randomized to treatment with either four double cycles of standard COPP/ABVD (cyclophosphamide, Oncovin, procarbazine, and prednisone/Adriamycin, bleomycin, vinblastine, and dacarbazine) chemotherapy (control arm) or a dose- and time-intensified COPP/ABVD regimen supported by 7 days of granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine, Prokine]) following each chemotherapy (intensified arm).Between April 1992 and June 1996, 264 patients from 28 institutions were randomized and 238 cases were eligible and evaluable (119 in the standard regimen and 119 in the time- and dose-intensified regimen). Age ranged from 17 to 71 years (mean, 37 years) with a proportion of 64% male; 21% of the patients had stage IIB disease; 51%, stage III; and 28%, stage IV. A total of 182 patients (75%) completed all cycles, while 62 (25%) stopped or switched treatment earlier.
If dose intensity was calculated according to the Hryniuk method from the drugs actually given, considering all eight drugs, the ratios of dose intensity were as follows: cycle 1, 0.96 vs. 1.35; cycle 2, 0.91 vs 1.22; cycle 3, 0.90 vs 1.13; cycle 4, 0.92 vs 1.22. The dose intensity for the whole treatment was 0.93 (control) vs 1.24 (intensified arm; P < .0001).
Infectious complications occurred in 53% of the control group and 62% of the intensified group, with grade 3-4 infection in five vs nine patients, respectively. Other adverse events were equally distributed, with the exception of musculoskeletal pain, rash and skin disorders, and headache, which occurred more often in the intensified arm (9.4% vs 14.6%, 5.6% vs 8.4%, and 9.5% vs 24.4%, respectively).
Complete remissions were achieved in 65% vs 81% in the control vs intensified groups (P < .003 by chi-square test), partial responses in 25% vs 16%, and disease progression in 7.6% vs 1.7%. Survival data are still incomplete but so far are in line with the response rates.
CONCLUSION: These preliminary data show that an intensified GM-CSFsupported COPP/ABVD regimen can be administered with acceptable toxicity and improved response rate, which is a prerequisite for improved survival in Hodgkins disease.