Phase I Study of Two Different Schedules of Bortezomib and Pemetrexed in Advanced Solid Tumors with Emphasis on Non-small Cell Lung Cancer.
J Thorac Oncol. 2007 Dec;2(12):1112-1116.
Davies AM, Ho C, Metzger AS, Beckett LA, Christensen S, Tanaka M, Lara PN, Lau DH, Gandara DR.
*University of California, Davis Campus, Sacramento, California; †British Columbia Cancer Agency, Vancouver, British Columbia, Canada; and ‡Marin Cancer Institute, Greenbrae, California.
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. |
