Title: Retrospective Analysis of Curcumin in Cervical Cancer Patients Post Radiotherapy

Authors: Nisarga Vontikoppal Manjunatha, Divyashree Shivalingaiah Jayashankar, Harshitha Kesargere Ramesh, Anu Kodihalli Raju, Vijayalaxmi Patil, Lokesh Vishwanath, Naveen Thimmiah, Sridhar Poojar, Vijay Calmuge Raghu

 DOI: https://dx.doi.org/10.18535/jmscr/v8i1.83

Abstract

Aim of the Study: To Evaluate the Effect of Curcumin on Toxicity and Outcomes in Cervical Cancer patients Post Radiotherapy.

Material and Methods: 60 Cervical Cancer patients who received definitive Chemo radiation and Brachytherapy were selected for the study. Patients received External beam Radiotherapy by 3DCRT technique to a total dose of 45-50GY with concurrent Platinum based chemotherapy of 5cycles and Brachytherapy was delivered by HDR technique, limiting the Bladder and Rectal doses to 75-80GY and 70-75GY respectively.

Of these, 30 Patients received Tab. Curcumin 500mg BID for a minimum period of 3 months post Radiotherapy during Follow-up and were compared with patients of similar characteristics kept only under Observation. The toxicity and outcomes post Radiotherapy was analyzed. The incidence of Radiation Dermatitis, Radiation Cystitis and Radiation Proctitis was analyzed.

Results: At 3 months post Radiotherapy, Radiation Dermatitis was seen in 20 out of 30 patients in the observation arm with Grade I toxicity in 12 patients, Grade II toxicity in 6 patients and Grade III toxicity in 2 patients compared to12 patients  having Grade I toxicity who received Curcumin (p=0.038) which was significant. Radiation Cystitis was seen in 21 patients in the observation arm with Grade I Toxicity in 16 Patients, Grade II Toxicity in 4 Patients and Grade IV Toxicity in 1patientcompared to 12patients with Grade I Cystitis in Curcumin arm (p=0.0198) which was  significant. Radiation Proctitis was seen in 23 patients in the observation arm with Grade I toxicity in 14 Patients and Grade II Toxicity in 9 patients compared to 8 patients with Grade I proctitis and 1 patient with Grade II toxicity in Curcumin arm (p=0.001) which was significant. There was no evidence of disease in 25 patients and only 5 patients had Stable disease in Curcumin arm compared to 6patients with Stable disease and 4patients with Progressive disease and no evidence of disease was seen in 20 patients in Observation arm.

Conclusions: Radiation Dermatitis, Cystitis and Proctitis are well known complications of radiation treatment in Carcinoma Cervix patients. Early detection and treatment reduces the grade of toxicity and improves Quality of life. The use of Curcumin post radiation definitely reduces the side effects and thereby improves the therapeutic ratio. Better local control with Curcumin must also be proved with large randomized control trials addressing all the bias. With the advent of nano-curcumin there is better absorption and bio- availibility for enhanced effects of curcumin and improving the quality of life.  The optimal dosage and duration of curcumin post radiotherapy to be administered is still investigational.

Keywords: Curcumin, Dermatitis, Cystitis, Proctitis, Cervical Cancer, Radiotherapy.

References

  1. Bray F et.al. Global cancer statistics 2018: GLOBOCAN estimates of Incidence and mortality worldwide for 36 Cancers in 185 Countries: CA CANCER J CLIN 2018; 68:394-424.
  2. Kidwai Memorial Institute of Oncology, Department of Epidemiology & Biostatistics, Hospital Based Cancer Registry Annual Report 2015.
  3. Goel A, Aggarwal BB: Curcumin, the golden spice from Indian Saffron, is a chemo sensitizer and radio sensitizer for tumors and chemo protector and radio protector for normal organs. Nutr Cancer 2010; 62:919-930.
  4. Li M, ZhaNG z, Hill DL, Wang H, Zhang R. Curcumin, a dietary component, has anticancer, chemo sensitization, and radio sensitization effect by down regulating the MDM2 oncogene through the P13K/mTOR/ETS2 pathway. Cancer Res 2007; 67:1988-1996.
  5. Sandur SK et.al: Curcumin modulates the radio sensitivity of colorectal cancer cells by suppressing constitutive and inducible NF-Kappa-B activity. Int J Radiat Oncol Biol Phys 2009; 75:534-542.
  6. Wei J et. al. Radiation induced skin reactions: mechanism and treatment. Cancer management and Research 2019:11 167-177.
  7. Yang L, LV Y(2012):Possible risk factors associated with radiation Proctitis or Radiation cystitis in patients with cervical carcinoma after radiotherapy. Asian Pac J Cancer Prev, 13, 6252-5.
  8. Mallick S, Madan R, Julka PK, Rath GK. Radiation Induced Cytitis and Proctitis-Prediction, Assessment and Management. Asian Pac J Cancer Prev .16(14),5589-5594.
  9. Ryan JL, Heckler CE, Ling M et al. Curcumin for Radiation dermatitis: A randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res.2013; 180(1):34-43.
  10. Rao S et.al: The Indian spices Turmeric delays and Mitigates Radiation-Induced Oral Mucositis in Patients Undergoing Treatment for Head and Neck Cancer: An Investigational study. Integr Cancer Ther 2014; 13:201-210.
  11. Patil K, Gudledgud MV, Kulkarani PK, Keshari D, Tayal S: Use of curcumin mouth rinse in Radio-Chemotherapy Induced Oral Mucositis Patients: A Pilot study . J Clin Diag Rs 2015; 9:59-62.
  12. Chendil D, Ranga RS, Meigooni D, Sathishkumar S, Ahmed MM: Curcumin confers radio sensitizing effect in prostate cancer cell line PC-3.Oncogene 2004;23:1599-1607.
  13. Akpolat M,Kanter M,Uzal MC.Protective effects of curcumin against gamma radiation-induced ileal mucosal damage. Arch Toxicol 2009; 83:609-617(Turkish Study).
  14. Montana GS, Fowler WC (1989). Carcinoma of the cervix: Analysis of Bladder and rectal Radiation dose and complications. Int J Radiat Oncolo Biol Phys, 16, 95-100.
  15. Zelefsky MJ, Levin EJ, Hunt M et al (2008): Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated Radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys, 70, 1124-9.
  16. Kunnumakkara AB et.al: Curcumin sensitizes human colorectal cancer xenografts in nude mice to gamma-radiation by targeting nuclear factor kappa B-regulated gene products. Clin Cancer Res 2008; 14:2128-2136.
  17. Jagetia GC. Radioprotection and Radio sensitization by curcumin. Adv Exp Med Biol 2007; 595:301-320.
  18. Verma V: Relationship and interactions of curcumin with radiation therapy. World J Clin Oncol 2016; 7(3):275-283.

Corresponding Author

Anu Kodihalli Raju

Post Graduate, Department of Radiation Oncology, Kidwai Memorial Institute of Oncology, Bengaluru-29