TY - JOUR
T1 - Bortezomib (PS-341) in relapsed or refractory extensive stage small cell lung cancer
T2 - A Southwest Oncology Group phase II trial (S0327)
AU - Lara, Primo N
AU - Chansky, Kari
AU - Davies, Angela M.
AU - Franklin, Wilbur A.
AU - Gumerlock, Paul H.
AU - Guaglianone, Perry P.
AU - Atkins, James N.
AU - Farneth, Nichole
AU - Mack, Philip
AU - Crowley, John J.
AU - Gandara, David R
PY - 2006/11
Y1 - 2006/11
N2 - BACKGROUND: In preclinical models, the proteasome inhibitor bortezomib (PS-341) inhibits the growth of small cell lung cancer (SCLC) by inhibiting the antiapoptotic Bcl-2 signaling pathway. We conducted a phase II trial of PS-341 in previously treated patients with platinum-sensitive and -refractory extensive stage SCLC to determine response rate, toxicity, and survival. METHODS: Patients with histologically confirmed SCLC, measurable disease, Zubrod performance status 0-1, and previous treatment with platinum-based therapy were enrolled. They were stratified by platinum-sensitivity status: sensitive (relapse >90 days after platinum) or refractory (progression during or ≤90 days after platinum). PS-341 was administered at 1.3 mg/m intravenously on days 1, 4, 8, and 11 every 21 days. RESULTS: Of 56 eligible patients, 28 were platinum sensitive and 28 refractory. Twenty-nine patients (52%) had received two or more previous chemotherapy regimens. One platinum-refractory patient had a confirmed partial response. A majority of assessable patients (91%) progressed. Median progression-free survival and overall survival were 1 month and 3 months, respectively. Ten patients (18%) discontinued treatment due to adverse events or side effects. CONCLUSION: Although PS-341 induced a response in a patient with platinum-refractory disease, it has limited single-agent activity in this heavily pretreated cohort. As shown in preclinical models, testing of PS-341 in combination with an apoptotic trigger such as chemotherapy, is a rational clinical approach. A trial of topotecan plus PS-341 has been initiated to test this concept.
AB - BACKGROUND: In preclinical models, the proteasome inhibitor bortezomib (PS-341) inhibits the growth of small cell lung cancer (SCLC) by inhibiting the antiapoptotic Bcl-2 signaling pathway. We conducted a phase II trial of PS-341 in previously treated patients with platinum-sensitive and -refractory extensive stage SCLC to determine response rate, toxicity, and survival. METHODS: Patients with histologically confirmed SCLC, measurable disease, Zubrod performance status 0-1, and previous treatment with platinum-based therapy were enrolled. They were stratified by platinum-sensitivity status: sensitive (relapse >90 days after platinum) or refractory (progression during or ≤90 days after platinum). PS-341 was administered at 1.3 mg/m intravenously on days 1, 4, 8, and 11 every 21 days. RESULTS: Of 56 eligible patients, 28 were platinum sensitive and 28 refractory. Twenty-nine patients (52%) had received two or more previous chemotherapy regimens. One platinum-refractory patient had a confirmed partial response. A majority of assessable patients (91%) progressed. Median progression-free survival and overall survival were 1 month and 3 months, respectively. Ten patients (18%) discontinued treatment due to adverse events or side effects. CONCLUSION: Although PS-341 induced a response in a patient with platinum-refractory disease, it has limited single-agent activity in this heavily pretreated cohort. As shown in preclinical models, testing of PS-341 in combination with an apoptotic trigger such as chemotherapy, is a rational clinical approach. A trial of topotecan plus PS-341 has been initiated to test this concept.
KW - Bcl-2
KW - Bortezomib
KW - Proteasome inhibition
KW - Small cell lung cancer
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U2 - 10.1097/01243894-200611000-00013
DO - 10.1097/01243894-200611000-00013
M3 - Article
C2 - 17409985
AN - SCOPUS:34247855046
VL - 1
SP - 996
EP - 1001
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 9
ER -