Phase II trial of temsirolimus in patients with relapsed or refractory multiple myeloma.
In a phase II trial, 16 patients with relapsed refractory multiple myeloma received temsirolimus 25mg I.V. weekly until progression. One partial response and 5 minor responses were observed for a total response rate of 38%. The median time to progression was 138 days. Grade 3-4 toxicity included fatigue (n=3), neutropenia (n=2), thrombocytopenia (n=2), interstitial pneumonitis (n=1), stomatitis (n=1) and diarrhea (n=1). Clinical activity was associated with a higher area under the curve (AUC) and maximal reduction in phosphorylated p70(S6)K and 4EBP1 in peripheral blood mononuclear cells. At the dose and schedule used, temsirolimus had low single agent activity. Investigation of alternate dosing schedules and use in combinations is indicated.
Farag
Sherif S
SS
Departments of Internal Medicine and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, United States. ssfarag@iupui.edu
Zhang
Shuhong
S
Jansak
Buffy S
BS
Wang
Xiaojing
X
Kraut
Eric
E
Chan
Kenneth
K
Dancey
Janet E
JE
Grever
Michael R
MR
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D012008:Recurrence; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000970:Antineoplastic Agents; C401859:temsirolimus; D020123:Sirolimus