Effect Of NESEM™/s2013 In Indian Population Undergoing Conventional Treatment For The Malignancies Of The Head & Neck, Git, Ovary, Breast And Lung As An Adjunct

Abstract

Background: NESEM ™/S2013, 500mg capsules were prepared by NPP Ltd containing the extracted Secondary Plant Metabolites (eSPMs): S40, S54, S55. These eSPMs were identified to be biologically active using human cells expressing cancer specific monooxygenase enzymes. Extensive bioavailability assessments were carried out. An optimized blend was encapsulated in 500mg, size zero, two-piece, hard shell, vegetarian capsules (Vcaps). (Notes: NESEM™’s are produced through the shikimate pathway by natural elicitation mechanisms; NESEM™ is an acronym for Naturally Elicited Specifically Extracted Molecules). It has been demonstrated in the past studies that NESEMTM/S2013s are phyto nutrients classified as phytoalexins that function through multiple mechanisms. One of the mechanisms is the intrinsic metabolism performed by CYP1B1, a universal cancer marker resulting in disturbances of cell cycling processes triggering apoptosis. There is limited availability of these phytonutrients in our diet due to modern day agricultural practices and food processing. Phytoalexins are produced as a way of defense mechanism, in response to infection or attack by predators. The purpose of this investigation is determining the effect of NESEM™/S2013 on Quality of Life (QoL) and survival in tandem to routine cancer therapy in malignancies of the Head & Neck, GIT, Ovary, Breast and Lung. Patients and methods: This study was a two-arm randomized controlled trial with a cohort of 102 patients. The patients presented with malignancies of Head & Neck, Lung, Breast, GIT, and Ovary. The study subjects in the two groups were randomized to either receive chemotherapy, radiotherapy and surgery or a combination of two or more therapies. Both the groups were given Vitamin C and B complex. The test group along with the above received NESEM™/S2013 (three capsules of 500 mg each of NESEM™/S2013 500mg was given as leader/loading dose for a month followed by two capsules of 500 mg each of NESEM™/S2013 till discontinuation or death). Minus the NESEM™/S2013, the control group was treated same as the test group. Results: In the Head & Neck Cancer patients, the mean overall survival (OS) was significant, p=0.0441. In the test arm, average OS was 15.91 ±10.73 months compared to 8.0 ± 5.83 months in the control group. This represents a 99% increase in survivability for the NESEM™/S2013 arm. In subjects with lung cancer, the average OS in the test group was 8.708± 9.006 months compared to 2.292 ±1.484 months in the control group. The average OS was significant, p=0.0234. This represents a 280% increase in survivability for the NESEM™/S2013 arm. In patients with cancer of GIT, the mean OS in the NESEM™/S2013 arm was 10.000 ± 10.317 months compared to was 3.550 ± 3.700 months in the control arm which was significant (p=0.0792). This represents a 182% increase in survivability for the NESEM™/S2013 arm. In patients with ovarian cancer, the average survival was 17.63 ± 7.19 months in the NESEM™/S2013 arm compared to 6.63 ± 7.56 in the control arm, that is statistically significant (p=0.0099), representing an increase of 166% in survivability for the NESEM™/S2013 arm. In patients with breast cancer, the mean survival in the test arm compared to control arm was statistically not significant, p=0.9073. The breast cancer patients exhibited the average survival in the test arm as 21.80 ± 6.96 months compared to 22.10 ± 4.01 months in the control group. At completion of 24 months (3 months post-study), 9 subjects from the NESEM™/S2013 arm (90%) and 7 subjects from the control arm (70%) were alive representing a 29% increase in survivability for the NESEM™/S2013 arm. The overall survival (OS) was significant in the NESEM™/S2013 arm (14.480± 10.036 months) compared to the control arm (8.333 ± 8.507 months), p=0.0012, representing an increase in survival rate of 75%. The mean Eastern Cooperative Oncology Group (ECOG) Performance score was 1.12 ± 0.773 in the NESEM™/S2013 arm (n=51) compared to 1.58 ± 0.8593 in the control arm (n=51) which was statistically significant (p=.00591). The Hamilton Anxiety (HAM-A) scores in both arms was non-significant (p=0.97), 2.4314 ± 2.9138 in the NESEM™/S2013 arm (n=51) versus 3.0612 ± 3.4666 in the control arm (n=51). The mean The Patient-Generated Subjective Global Assessment (PG-SGA) scores was non-significant too (p=0.312209) were 6.4688 ± 2.8959 in the NESEM™/S2013 arm (n=51) versus 7.625 ± 5.7291 in the control arm (n=51). Conclusion: The literature on the efficacy of NESEM™/S2013s as adjunct to cancer treatment is sparse. Only one case and a series case report have been reported thus far. No Randomized controlled clinical trials with NESEM™/S2013s as adjunct with conventional cancer treatment have been ever initiated. It, hence became almost critical to study the role of NESEM™/S2013 in a randomized controlled manner. The study was designed to compare the QoL and survival of 102 patients with cancers of the Head & Neck, Lung, Breast, GI, and Ovaries when NESEM™/S2013 were added to their prescribed treatment. The study showed to improve the OS in malignancies of the Head & Neck, Lung, GI, and Ovaries when NESEM™/S2013s were added to same TNM based treatment. NESEM™/S2013s impacted the ECOG scores positively but had no significant effect on HAM–A or PG-SGA. It can be concluded that NESEM™/S2013s may have played a role in improvement of OS and ECOG status. Both CYP1B1 pathway and NESEM™/S2013 were found to be encouraging findings for the improved treatment of cancer. It is also reassuring that these solutions pose no additional toxicities or side effects. Randomized trials in larger set-ups would further give insights and confirmation in the role of NESEM™/S2013s.