TY - JOUR
T1 - Tanespimycin monotherapy in relapsed multiple myeloma
T2 - Results of a phase 1 dose-escalation study
AU - Richardson, Paul G.
AU - Chanan-Khan, Asher A.
AU - Alsina, Melissa
AU - Albitar, Maher
AU - Berman, David
AU - Messina, Marianne
AU - Mitsiades, Constantine S.
AU - Anderson, Kenneth C.
PY - 2010/8
Y1 - 2010/8
N2 - Tanespimycin, a heat shock protein 90 (HSP90) inhibitor, induces apoptosis in drug-sensitive and -resistant MM cell lines and in tumour cells from patients with relapsed MM. In this phase 1 dose-escalation study, the safety, plasma pharmacokinetics, and biological/antitumour activity of tanespimycin were evaluated in heavily pretreated patients with relapsed/refractory MM. Tanespimycin (150-525 mg/m2) was given on days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles. Non-haematological AEs included diarrhoea (59%), back pain (35%), fatigue (38%), and nausea (35%); haematological AEs included anaemia (24%) and thrombocytopenia (21%). One patient (3%) achieved minimal response (MR), with a progression-free survival (PFS) of 3 months, a 41% decrease from baseline in urine M protein, and a 33% decrease from baseline in serum M protein. Fifteen patients (52%) achieved SD with a median PFS of 2·1 months; 5/15 had reductions in serum M protein ranging from 7% to 38% and in urine M protein ranging from 6% to 91%. Mean HSP70 levels increased from day 1 h 0 to day 1 h 4 with further increases on day 11 h 0 and day 11 h 4, consistent with a therapeutic treatment effect. Tanespimycin monotherapy was well tolerated and demonstrated activity across all doses tested.
AB - Tanespimycin, a heat shock protein 90 (HSP90) inhibitor, induces apoptosis in drug-sensitive and -resistant MM cell lines and in tumour cells from patients with relapsed MM. In this phase 1 dose-escalation study, the safety, plasma pharmacokinetics, and biological/antitumour activity of tanespimycin were evaluated in heavily pretreated patients with relapsed/refractory MM. Tanespimycin (150-525 mg/m2) was given on days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles. Non-haematological AEs included diarrhoea (59%), back pain (35%), fatigue (38%), and nausea (35%); haematological AEs included anaemia (24%) and thrombocytopenia (21%). One patient (3%) achieved minimal response (MR), with a progression-free survival (PFS) of 3 months, a 41% decrease from baseline in urine M protein, and a 33% decrease from baseline in serum M protein. Fifteen patients (52%) achieved SD with a median PFS of 2·1 months; 5/15 had reductions in serum M protein ranging from 7% to 38% and in urine M protein ranging from 6% to 91%. Mean HSP70 levels increased from day 1 h 0 to day 1 h 4 with further increases on day 11 h 0 and day 11 h 4, consistent with a therapeutic treatment effect. Tanespimycin monotherapy was well tolerated and demonstrated activity across all doses tested.
KW - 17-AAG
KW - HSP70
KW - HSP90
KW - Multiple myeloma
KW - tanespimycin
UR - http://www.scopus.com/inward/record.url?scp=77955141041&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955141041&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2010.08265.x
DO - 10.1111/j.1365-2141.2010.08265.x
M3 - Article
C2 - 20618337
AN - SCOPUS:77955141041
SN - 0007-1048
VL - 150
SP - 438
EP - 445
JO - British journal of haematology
JF - British journal of haematology
IS - 4
ER -