Phase I study of two different schedules of bortezomib (BORT) and pemetrexed (PEM) in advanced solid tumors.


17051 Background: BORT(PS-341) is a small molecule proteasome inhibitor while PEM, a multi-targeted antifolate, inhibits multiple enzymes involved in purine/pyrimidine formation. Both are approved anti-cancer agents. We examined the safety and tolerability of two different schedules of BORT and PEM in patients with advanced solid tumors. METHODS Two dose escalation trials (Arm A and Arm B) were conducted simultaneously. PEM was given every 21 days in both arms (500-600 mg/m2 IV). Arm A: BORT was given D1,4,8 &11 (0.7-1.3 mg/m2). Arm B: BORT was given D1 & 8 (1.0-1.6 mg/m2). All patients received vitamin B12, folic acid and decadron. Dose limiting toxicity (DLT) was defined as: grade (GR) 4 platelets (plts) (≤25K); GR 3 plts (25K-49,999K) with bleeding, requirement for transfusion, or lasting > 7 days; febrile neutropenia; GR3 ANC (ANC ≤1.0 × 109) with documented infection, or any ≥ GR3 non-heme toxicity. RESULTS 18 patients have been treated on 3 of the 4 planned dose levels. Tumor types included lung (12), prostate (2), breast (1), thymus (1), head & neck (1) and adenoid cystic carcinoma (1). Pt. characteristics: Median age 65 years; Sex M/F = 7/11; Performance Status ≤1/2 = 18/0. There have been no DLTs in either arm (Dose level 3-Arm A: PEM 500 mg/m2, BORT 1.3 mg/m2; Arm B:PEM 500 mg/m2, BORT 1.6 mg/m2). Most common GR3/4 toxicities were: neutropenia 27% and lymphopenia 11%. Of 17 evaluable patients: 1 had partial response, 11 had stable disease, 5 had progressive disease. Mean number of cycles: 4. Arm A had more doses held during the first cycle than Arm B (6 doses held vs. 1 dose held). Accrual to the final dose level in both arms is ongoing. CONCLUSIONS 1) PEM in combination with BORT is feasible and tolerable. 2) Thus far, there are no differences in toxicity between the arms. 3) A randomized, multi-institutional phase II study will examine the efficacy of these two schedules in patients with NSCLC. No significant financial relationships to disclose.

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@article{Metzger2006PhaseIS, title={Phase I study of two different schedules of bortezomib (BORT) and pemetrexed (PEM) in advanced solid tumors.}, author={Alex S Metzger and P. Lara and Derick H. M. Lau and Peter P O Mack and Paul H. Gumerlock and David R . Gandara and Angela M. Davies}, journal={Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, year={2006}, volume={24 18_suppl}, pages={17051} }