Sequential Chemotherapy and Late Intensification for Malignant Lymphomas of Aggressive Histologic Type FERNANDO CABANILLAS, M.D. MICHAEL A. BURGESS, M.D. GERALD P. BODEY, M.D. EMIL J. FREIREICH, M.D. Houston, zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Te xas From the Department of Developmental Thera- peutics, University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor In- stitute, Houston, Texas. Requests for reprints should be addressed to Dr. Fernando Cabanillas, Department of Developmental Therapeutics, University of Texas System Cancer Center, Texas Medical Center, 6723 Bertner Avenue, Houston, Texas 77030. Manuscript accepted May 26, 1962. Fifty-six patients with malignant iymphoma of aggressive histologic type (51 large ceil, three diffuse undifferentiated, and two nodular mixed) were treated with three non-cross-resistant combination chemotherapy regimens that were introduced sequentially according to the response to therapy. The objective was to increase the complete remission rate by changing the chemotherapy regimen early if the patient did not attain a complete remission after three courses of treatment. Late intensification was also used with the aim of prolonging the duration of complete remission. The overall com- plete remission rate obtained with this approach was 82 percent (100 percent in stages I to iii and 88 percent in stage IV). The pro- jected survival at four years is 71 percent (93 percent for stages I to iii and 55 percent for stage IV). Eighty percent of patients with complete remission are projected to have continued remission at four years. Compared with previous experience with Adriamycin- based combination regimens, these results represent an improve- ment in remission and survival parameters. The most significant gains occurred in the prolongation of survival of patients witti stages I to ill disease and in the improved duration of complete remission of patients with stage IV disease. Toxicity included 15 documented infections among 320 courses of therapy, four cases of congestive heart failure, one case of bieomycin lung toxicity, and two cases of liver dysfunction. This multiple combination regimen represents an improvement over previous results utilizing Adriamycin-based combination chemotherapy. The sensitivity of the malignant iymphomas to a number of chemo- therapy agents has led to the use of drug combinations that have substantially improved the prognosis of these disorders during the last decade. The recent introduction of drugs such as Adriamycin and bleomycin has also been partly responsible for these advances. De- spite these achievements, the proportion of patients with advanced lymphoma of aggressive histologic type that can be cured is in the range of only 25 to 50 percent [l-8]. The remaining patients are not cured because of two major obstacles: (1) failure to achieve complete remission in approximately one third of the patients, (2) relapse from complete remission in approximately one fourth to one half of the patients. In 1977, we designed a protocol aimed at improving the complete remission rate and decreasing the relapse rate. In order to accomplish the first objective, we proposed to administer three courses of combination chemotherapy (CHOP) and if complete re- mission was not achieved, as determined by restaging procedures, the treatment regimen was changed to a second combination. Finally, 362 March 1983 The American Journal of Medicine Volume 74