PS-341 and gemcitabine in patients with metastatic pancreatic adenocarcinoma: a North Central Cancer Treatment Group (NCCTG) randomized phase II study

Abstract

The use of PS-341 alone or in combination with gemcitabine did not result in an overall survival and RR better than that expected for gemcitabine alone. Based on the lack of efficacy and the toxicity seen in our trial, there does not appear to be a role for PS-341 in pancreatic adenocarcinoma with either of the schedules used in this trial.

Targeting apoptosis in solid tumors: the role of bortezomib from preclinical to clinical evidence

“…Numerous other clinical trials are being conducted at present to investigate the potential of bortezomib in the treatment of NSCLC. Alberts et al [103] investigated the efficacy of bortezomib monotherapy compared with the combination of bortezomib and gemcitabine in patients with metastatic pancreatic adenocarcinoma. The response rate for patients receiving combination therapy was 10%, the same as that expected for gemcitabine alone.…”

Combined autophagy and proteasome inhibition

“…Plasma cells are terminally differentiated B-cells, and bortezomib is also active in other B-cell malignancies, [3][4][5][6][7][8] but has limited efficacy in solid tumors. [9][10][11][12] One possible explanation for this difference in efficacy is the unique burden of misfolded proteins faced by malignant plasma cells, which generate large amounts of a single amino acid sequence as they produce the monoclonal immunoglobulin characteristic of myeloma. Preclinical evidence suggests that the efficacy of proteasome inhibitor therapy depends on the ability of malignant plasma cells to clear misfolded proteins through proteasomal degradation.…”

Bortezomib is ineffective in an orthotopic mouse model of pancreatic adenocarcinoma

“…The phase II trial of the North Central Cancer Treatment Group investigated bortezomib monotherapy versus bortezomib plus gemcitabine in patients with metastatic pancreatic carcinoma. Patients who received bortezomib monotherapy had a median survival of just 2.4 and of 4.8 months when gemcitabine has been added (33).…”