Toxicity of Bortezomib: Is There An Influence of Application Rates of Doxorubicin and Dexamethason Administration?a Clinical Monitoring

Abstract

Background: Bortezomib has shown significant anti-tumor activity in multiple myeloma. There are varied protocols including bortezomib, doxorubicin and dexamethason with different application rates. We observed in a retrospective analysis a wide range of toxicity, so that we have to modified our standard approach. The purpose of our analysis was to assess the frequency of toxicity and their alteration after changing the protocol. Patients and methods: Eleven patients were treated for two 28-day cycles using our standard protocol. Bortezomib was given at 1.3 mg/m2 (days 1,4,8,11) and dexamethason at 40 mg (days 1–4, 9–12, 17–20) as well as doxorubicin at 9 mg/m2 (days 1–4). Seven patients received a third modified cycle composed of Bortezomib at 1.3 mg/m2 (days 1,4,8,11), dexamethason at 40 mg days 1–4 and doxorubicin at 20 mg/m2 days 1 and 4. Results: One patient had unergone prior autologous transplantation, the other ten patients (90%) were newly diagnosed. All patients reported moderate peripheral neuropathic pain during the first two cycles. Eight patients (72%) developed severe adverse effects, twenty-five percent during the first cycle and seventy-five percent after the second one. The age of the affected patients range from 65 to 77 years (average age 70.5 years), the mean age of the unaffected is 64.7 years (54 to 72 years). Grade 3–4 toxic effects included infections (100%), neutropenia (25%), acute renal insufficiency (25%) and pulmonary edema (1 patient). Within the group of infections a pneumonia were diagnosed in six patients (75%), herpes zoster in two patients (25%) and an erysipelas in one patient. Two patients (25%) with pneumonia are died from a septic-toxic shock. The seven patients receiving the modiefied third cycle were without any grade 3–4 toxicity. Conclusions: The age seems to have an influence on adverse effects (p=0.19) but there is a high significant benefit concerning the toxicity of bortezomib depending on application rates of doxorubicin and dexamethason.