TY - JOUR
T1 - Phase I study of two different schedules of bortezomib and pemetrexed in advanced solid tumors with emphasis on non-small cell lung cancer
AU - Davies, Angela M.
AU - Ho, Cheryl
AU - Metzger, Alex S.
AU - Beckett, Laurel A
AU - Christensen, Scott D
AU - Tanaka, Michael
AU - Lara, Primo N
AU - Lau, Derick H
AU - Gandara, David R
PY - 2007/12
Y1 - 2007/12
N2 - INTRODUCTION: Bortezomib and pemetrexed are approved anticancer agents with non-overlapping mechanisms of action and toxicity. We examined the safety and tolerability of pemetrexed in combination with two different schedules of bortezomib in patients with advanced solid tumors. METHODS: Two separate dose-escalating arms (arm A and arm B) were conducted simultaneously. Patients received pemetrexed on day 1 (D1) (500-600 mg/m IV) every 21 days. In arm A, bortezomib was given twice weekly (0.7-1.3 mg/m on D1, 4, 8, and 11). In arm B, bortezomib was given weekly (1.0-1.6 mg/m on D1 and 8). RESULTS: We treated 27 patients on four dose levels in arm A and three dose levels in arm B. Tumor types included lung (n = 16), adenoid cystic carcinoma (n = 2), prostate (n = 2), sarcoma (n = 2), breast (n = 1), thymus (n = 1), head and neck (n = 1), and gastrointestinal(n = 2). Dose-limiting toxicities were seen in arm A only; grade 3 asthenia (n = 2), grade 3 transaminitis and dehydration (n = 1). The most common grade 3/4 toxicity was neutropenia. Of 26 evaluable patients, 2 patients had partial response (1 in arm A and 1 in arm B), 13 had stable disease (7 in arm A and 6 in arm B), and 11 had progression (6 in arm A and 5 in arm B). Of the 16 patients with non-small cell lung cancer, 2 (12.5%) had partial response and 9 had stable disease, for a disease control rate of 68.8%. Recommended phase II dose for arm A is pemetrexed 500 mg/m and bortezomib 1.3 mg/m twice weekly. For arm B, the recommended dose is pemetrexed 500 mg/m, bortezomib 1.6 mg/m weekly. CONCLUSIONS: Pemetrexed with bortezomib is feasible and tolerable at recommended single-agent doses. Based on the observed efficacy, a phase II study in non-small cell lung cancer is warranted.
AB - INTRODUCTION: Bortezomib and pemetrexed are approved anticancer agents with non-overlapping mechanisms of action and toxicity. We examined the safety and tolerability of pemetrexed in combination with two different schedules of bortezomib in patients with advanced solid tumors. METHODS: Two separate dose-escalating arms (arm A and arm B) were conducted simultaneously. Patients received pemetrexed on day 1 (D1) (500-600 mg/m IV) every 21 days. In arm A, bortezomib was given twice weekly (0.7-1.3 mg/m on D1, 4, 8, and 11). In arm B, bortezomib was given weekly (1.0-1.6 mg/m on D1 and 8). RESULTS: We treated 27 patients on four dose levels in arm A and three dose levels in arm B. Tumor types included lung (n = 16), adenoid cystic carcinoma (n = 2), prostate (n = 2), sarcoma (n = 2), breast (n = 1), thymus (n = 1), head and neck (n = 1), and gastrointestinal(n = 2). Dose-limiting toxicities were seen in arm A only; grade 3 asthenia (n = 2), grade 3 transaminitis and dehydration (n = 1). The most common grade 3/4 toxicity was neutropenia. Of 26 evaluable patients, 2 patients had partial response (1 in arm A and 1 in arm B), 13 had stable disease (7 in arm A and 6 in arm B), and 11 had progression (6 in arm A and 5 in arm B). Of the 16 patients with non-small cell lung cancer, 2 (12.5%) had partial response and 9 had stable disease, for a disease control rate of 68.8%. Recommended phase II dose for arm A is pemetrexed 500 mg/m and bortezomib 1.3 mg/m twice weekly. For arm B, the recommended dose is pemetrexed 500 mg/m, bortezomib 1.6 mg/m weekly. CONCLUSIONS: Pemetrexed with bortezomib is feasible and tolerable at recommended single-agent doses. Based on the observed efficacy, a phase II study in non-small cell lung cancer is warranted.
KW - Bortezomib
KW - Non-small cell lung cancer
KW - Pemetrexed
KW - Phase I
KW - Proteasome
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UR - http://www.scopus.com/inward/citedby.url?scp=37349100108&partnerID=8YFLogxK
U2 - 10.1097/JTO.0b013e31815ba7d0
DO - 10.1097/JTO.0b013e31815ba7d0
M3 - Article
C2 - 18090584
AN - SCOPUS:37349100108
VL - 2
SP - 1112
EP - 1116
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 12
ER -