Clinically, we are studying drug resistance in relapsed and refractory lymphomas and breast cancer. In Hodgkin's and non-Hodgkin's lymphomas, multi-drug resistance (mdr-1) is a possible mechanism of clinical drug resistance. Eligible patients undergo multiple tumor biopsies to assay for several drug resistance mechanisms and receive EPOCH chemotherapy, a regimen which was developed to overcome mdr-1. Patients who do not achieve a complete remission also receive R-verapamil, a blocker of mdr-1, in a Phase I/II setting. We are also studying the toxicity and efficacy of infusional taxol in relapsed and refractory breast cancer and lymphomas. Patients undergo multiple tissue biopsies for assessment of drug resistance mechanism including mdr-1, total cellular tubulin and tubulin mutations. A subset of relapsed patients are eligible to receive high-dose chemotherapy with ifosfamide, CBDCA and etoposide with autologous bone marrow rescue. These patients receive interleukin-1 (IL-1), which may modulate sensitivity to chemotherapy and protect stem cells. A Phase I/II trial is ongoing to study both the myelo-protective and cytotoxic properties of IL-1.
