Vit D

Pilot study: Paricalcitol for 1 month prior to resection (n = 12) ➔ Increase T cell penetration into the tumor.9

HCQ

Phase II: HCQ without chemo (n = 20) ➔ 2/20 (10%) had no progression at 2 months. Results insignificant.22

Phase II: HCQ + pre-op SCRT + Gem (n = 50) ➔ HCQ did not meaningfully impact survival.23

Phase II: HCQ + chemo (n = 57) ➔ More tumor destroyed, CA19-9 decreased, lower ratio of positive lymph nodes, greater apoptosis, less stromal activation, greater infiltration of CD4 and CD8 T cells, and increased PD-L1.24

Vit C

Phase I: IV Vit C + Gem (n = 9) ➔ Extended patients’ OS to 12 months vs. historical OS of 5.65 months.56

Phase I: IV Vit C + Gem and erlotinib (n = 9) ➔ 7 of 9 subjects had stable disease while only 2 had progressive disease.57

Metformin

Retro: Mt in DM with resectable PC (n = 19)/control (n = 25) ➔ 5-Year survival rates of 34% vs. 14%.72

Retro: Mt (n = 117)/control (n = 185) DM with PC ➔ 2-Year survival rate was 30.1% vs. 15.4%. OS was 15.2 months vs. 11.1 months. Statistical significance only in patients with nonmetastatic disease.73

Phase II: Mt + Gem and erlotinib (n = 60)/control (n = 61) in advanced metastatic disease ➔ No difference in OS.74

Phase II: Mt + PEXG (n = 31)/control (n = 30) in advanced disease ➔ No difference in OS.75

Retro: Mt (n = 336)/control (n = 644) ➔ OS of 9.9 months vs. 8.9 months. Statistical significance only in the locally advanced PC group.76

Statins

Retro: Simvastatin (n = 680)/atorvastatin (n = 149)/control (n = 1,747) ➔ 31% and 39% decrease in mortality.85

Retro: Statin (n = 118)/control (n = 1,643) ➔ 5-Year survival of 16.6% vs. 8.9% for nonusers. Simvastatin showed the greatest benefit.79

Retro: Simvastatin with resectable PC (n = 71)/control (n = 155) ➔ Improved OS.86

Retro: Statin use after diagnosis (n = 2,456)/control (n = 5,357) ➔ Improved OS in patients with grade 1/2 tumors with resection, but not in patients with higher-grade tumors.87

Phase II: Simvastatin + Gem 40 mg (n = 57) in stage 4 PC/control (n = 57) ➔ No significant difference in time to progression.89

Retro: Statins + erlotinib and Gem for unresectable PC (n = 17)/control (n = 163) ➔ Improved OS of 8.1 months vs. 3.9 months.90

Metformin/statin

Retro: PC patients (n = 12,572) ➔ Statin use improved OS; Mt use did not improve OS.77

Curcumin

Phase II: Curcumin 8 g/d daily without chemo (n = 21) ➔ 1 patient remained stable for >18 months and another patient had a dramatic but brief tumor response. Curcumin downregulated expression of NF-κB, COX-2, and other markers.127

Phase I/II: Curcumin 8 g/d + Gem in Gem-resistant PC patients (n = 21) ➔ Well tolerated with OS of 161 days (too small for analysis).128

Aspirin

No studies for PC treatment; only prevention.

Abbreviations: Vit D, vitamin D; HCQ, hydroxychloroquine; chemo, chemotherapy; pre-op SCRT, preoperative short-course chemoradiation; Gem, gemcitabine; Vit C, vitamin C; IV, intravenous; OS, overall survival; Retro, retrospective study; Mt, metformin; DM, diabetes mellitus; PEXG, cisplatin, epirubicin, capecitabine, and gemcitabine; PC, pancreatic cancer.