47P - Pharmacogenetics & treatment outcome in cancer patients receiving radio-chemotherapy

Date 17 April 2015
Event ELCC 2015
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Lung and other Thoracic Tumours
Translational Research
Surgery and/or Radiotherapy of Cancer
Presenter Sunishtha Yadav
Citation Annals of Oncology (2015) 26 (suppl_1): 10-14. 10.1093/annonc/mdv045
Authors S.S. Yadav1, V. Chauhan2, D. Parmar3
  • 1Aib, Biosciences, Amity University ACB & PDM, 201303 - Noida/IN
  • 2Biosciences, Amity University ACB & PDM, 201303 - Noida/IN
  • 3Developmental Toxicology Division, IITR, 226 001 - Lucknow/IN

Abstract

Aim/Background

In the recent years, evidences have been accumulated indicating that carcinogen/drug metabolizing genes and DNA-repair genes may play an important role in determining individual susceptibility to cancer & treatment outcomes. Pharmacogenetic variability associated with the drug metabolizing enzymes could be a major determinant of variations in treatment outcomes. The present study was designed to understand effect of Pharmacogenetic variability associated with Cytochrome P4502C19 (CYP2C19) on treatment outcomes in cancer patients.

Methods

The study group comprised 290 patients with Lung cancer (NSCLC) & Head & neck squamous cell carcinoma (HNSCC) and equal number of controls. Patients of NSCLC & HNSCC were treated with NACT (Neo adjuvant chemotherapy; 3 weekly 3 cycles), CT-RT (Concurrent chemoradiotherapy; every week 7 cycles) and ACT (Adjuvant chemotherapy; 3 weeks 6 cycles). Localised disease lesions treated with curative intent by surgery or radiation. Small lesions that were well lateralised were excised (partial glossectomy). Larger lesions where excision would compromise speech and swallowing ability were treated with radiotherapy. The response to radio-chemotherapy was based on 50% reduction in tumor size, 50% & above response as judged by clinical parameters, imaging, CTMRI, endoscopy techniques as per WHO criteria.

Results

Amongst the patients with wild type genotype of CYP2C19 (CYP2C19*1), 71% responded to the treatment of chemo- and radiotherapy (Responders) while 29% showed less than 20% response (Non-responders). Majority of the patients with CYP2C19*2 genotype were found to be non-responders (74%), while only 26% exhibited good response (responders). Likewise, amongst the PM with CYP2C19*3 genotype (5.33%), 50% responded to the treatment. Interestingly, 3 individuals amongst the cases carried both the PM genotypes (CYP2C19*2 & CYP2C19*3) of CYP2C19 and all three of them did not respond to the chemotherapeutic treatment.

Conclusions

It was demonstrated that CYP2C19 variants modify the treatment outcome in cases receiving combination of radio-chemotherapy.

Disclosure

All authors have declared no conflicts of interest.