Combined modality clinical trials for favorable B-cell neoplasms: lonidamine plus whole body hyperthermia and/or total body irradiation.

Favorable B-cell neoplasms provide an excellent clinical model to evaluate the use of systemic multimodality therapy as an approach to the problem of tumor cell heterogeneity. Inherent in this concept is the use of multiple antineoplastic agents to produce supra-additive cytotoxicity without sacrificing therapeutic index. The results of three completed clinical studies and complementary laboratory investigations are reviewed to illustrate an innovative approach to the nodular lymphomas and chronic lymphocytic leukemia. The clinical trials summarized include: A) the combination of 41.8 degrees C whole body hyperthermia (WBH) and the chemotherapeutic drug lonidamine; B) the use of total body irradiation (TBI) (12.5 cGy twice a week, every other week--total planned dose 150 cGy) and daily oral lonidamine; C) the juxtapositioning of TBI (with the same fraction schema) and 41.8 degrees C WBH x 75 min--initiated 10 min after TBI. Also presented is the laboratory rationale and early clinical results for combining lonidamine, TBI, and WBH.