Use of the hypoxic cell sensitizer etanidazole (SR-2508) with intravenous melphalan and prednisone in the treatment of multiple myeloma: a pharmacokinetic study.
OBJECTIVE
A study was undertaken adding the alkylating agent sensitizer etanidazole to intravenous melphalan and oral prednisone for patients with multiple myeloma. This study explored the toxicity profile of these agents when given together and assessed the ability to attain adequate serum levels of etanidazole to permit sensitization to occur.


METHODS
Etanidazole was administered intravenously in two doses of 3 g/m2 and 5 g/m2 90 min apart immediately prior to the administration of intravenous melphalan and oral prednisone for three consecutive cycles (total dose 24 g/m2). Patients received three additional cycles without etanidazole, allowing a comparison of hematologic toxicity from melphalan with and without etanidazole.


RESULTS
Hematologic toxicity was moderate (Grade 3 or 4), but severity was similar during cycles with and without etanidazole. Only one patient developed a Grade 1 peripheral neuropathy questionably related to etanidazole. Most patients had etanidazole levels of > or = 70 ug/ml for 7 h, a level felt to be necessary for sensitization to occur.


CONCLUSIONS
Etanidazole, administered as described, results in adequate serum levels for potential alkylating agent sensitization, without significant toxicity.
Shulman
L N
LN
Hematology-Oncology Division, Brigham and Women's Hospital, Boston, MA 02115.
Buswell
L
L
Kalish
L A
LA
Coleman
C N
CN
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017341:Etanidazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D008558:Melphalan / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011241:Prednisone / Q000008:administration & dosage
D017341:Etanidazole; D008558:Melphalan; D011241:Prednisone