Curcumin as adjuvant therapy to improve remission in myeloma patients: A pilot randomized clinical trial

Abstract

Background: The treatment for ineligible transplant multiple myeloma is melphalan prednisone. Curcumin has an anti-inflammatory and antiangiogenesis in cancer-directed to nuclear factor-kappa B (NF-kB) pathway. Interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and lactate dehydrogenase (LDH) were also involved in the pathogenesis of myeloma. No clinical study has evaluated the efficacy of curcumin in myeloma patients. To evaluate the efficacy of curcumin as adjuvant into melphalan prednisone in myeloma patients.

Methods: 33 myeloma patients at Dr. Kariadi General Hospital, Semarang, Indonesia during 2016-2017 were randomly assigned single-blindedly into MPC (n=17) and control group (n=16). The MPC group was treated with melphalan 4 mg/m2, prednisone 40 mg/m2 for 7 days, and curcumin 8 gram daily for 28 days. The MP control group was treated with melphalan, prednisone, and placebo. The primary endpoint was the overall remission. Pre- and post-treatment was examined for NF-κB, VEGF, TNF-α, IL-6, LDH, and CRP levels All data analyses were per protocol.

Results: There was a significant difference in overall remission between the MPC and MP control groups [75%vs 33.3%, x²=6.89, P=0.009]. A significant decrease of NF-κB, VEGF, TNF-α levels were shown in the MPC group compared with the MP control group. There was a significant decrease in IL-6 levels in a subgroup analysis of the MPC group. TNF-α levels had a significant correlation with remission [OR=1.35; (95%CI=1.03-1.76); P=0.03].

Conclusion: Curcumin has an efficacy in improving overall remission and decreasing NF-κB, VEGF, TNF-α, and IL-6 levels in myeloma patients.

Keywords: IL-6; Myeloma; NF-κB; Overall remission; TNF-α; VGEF.

Figure 1

Randomized, single-blind & parallel design of the study. Multiple myeloma patients were single-blindedly randomized to MPC (green) and MP+Placebo (blue) groups. Data collection including full blood count (FBC), urea, creatinine, NF-κB, IL-6, CRP, LDH, VEGF, were collected in the baseline and every cycle (28 days)

Figure 2

Consort of study Description: MPC: melphalan, prednisone, curcumin MP; melphalan, prednisone, placebo. Four patients in the treatment group died because of sepsis, anemia, and thrombocytopenia in the first-month treatment. ** Three patients in the control group died because of sepsis, melena, and anemia in the first-month treatment. One patient in the control group stopped taking medication because of flushing. One patient in the treatment group was lost of contact in the second monthly treatment. *** One patient in the control group died because of anemia and sepsis in the third-month treatment