In Phase I, patients will receive a combination of PS-341 (Velcade) and R115777 (Zarnestra) to determine the dose limiting toxicity (DLT). Once DLT is determined, patients in Phase II will be receive the maximum tolerated dose (MTD) to complete 8 cycles of therapy. Treatment will continue if there is evidence of continued response for 8 cycles. Patients will receive follow up to include normal laboratory evaluations at least every 3 months and a skeletal survey will be performed at least every 6 months.