Title: Palliative Radiotherapy with Concomitant and Maintenance Gefitinib for the Management of Locally Advanced Adenocarcinoma Lung Patients Unfit For Radical Treatment

Authors: Vikas Verma, Paramjeet Kaur (MD), Ashok K. Chauhan (MD), Yashpal Verma (MD), Anil Khurana (MD), Meenakshi Sharma

 DOI:  https://dx.doi.org/10.18535/jmscr/v5i6.210

Abstract

Purpose: To evaluate the feasibility and role of palliative radiotherapy and concomitant gefitinib and maintenance in locally advanced adenocarcinoma lung patients unfit for radical radiotherapy with respect to symptomatic relief with improvement in quality of life, local control, toxicity, progression free survival (PFS) & overall survival (OS).

Material and Methods: A total of thirty four (34) patients with stage III adenocarcinoma lung were accrued in the study who presented in the Department of Radiotherapy, PGIMS Rohtak from January 2015 to June 2016. Presenting symptoms were cough in 18, breathlessness in 23, expectoration with blood in 4 and chest pain in 24 patients. Male:female was 20:14. All accrued patients had KPS 40 to 60. These patients were treated with palliative EBRT 30 Gy in 10 fractions over 2 weeks and oral Gefitinib 250 mg once a day, from the first day of radiotherapy, concomitant & continued thereafter till disease progression. Median follow-up was 7 months (range 2-24 months). The patients were assessed for symptomatic relief, local control, toxicity, progression free survival & overall survival.

Results: All patients had tolerated the treatment well and no significant drug induced toxicity was observed. More than ≥25% relief in cough, chest pain, haemoptysis and dyspnoea was observed in 55%, 54%, 100% & 74% of patients respectively. Partial response was observed in 68% patients while remaining had stable disease at 1st follow up. At 6th follow up, 38% & 12% patients maintained their partial response and stable disease status respectively. Diarrhoea and skin rashes were two toxicities which were observed in 38% and 59% patients. Median PFS & OS were 6 months (range 2 – 24 months) and 7 months respectively. Prognostic factors like smoking, EGFR overexpression, pre and post treatment quality of life were statistically significant in improving the OS (p-value 0.0010, 0.0031, 0.006, 0.0001 respectively). EGFR overexpression status and post-treatment quality of life were also found to be statistically significant in improving the PFS (p-value<0.0001 and 0.0004 respectively).  

Conclusion: The present study demonstrates the favourable safety profile, ease of administration and a promising outcome in terms of results attained with palliative radiotherapy concurrent with gefitinib, in adenocarcinoma lung patients presenting with locally advanced stage not amenable to radical radiotherapy. However, the results need to be warranted by future studies with the larger samples in order to recommend it as a standard protocol.

References

1.      Singh N, Aggarwal AN, Gupta D, Behera D, Jindal SK. Unchanging clinic-epidemiological profile of lung cancer in north India over three decades. Cancer Epidemiol. 2010;34:101-4.

2.      Agrawal S. Challenges in optimizing chemoradiation in locally advanced non-small cell lung cancers in India. South Asian Journal of Cancer. 2013;2(4):265-71.

3.      Behera D, Balamugesh T. Lung cancer in India. Indian J Chest Dis Allied Sci. 2004;46:269-81.

4.      Chang YJ, Bradley JD, Govindan R, Komaiki R. Lung. In: Halperin EC, Perez CA, Brady LW, editors. Perez and Brady's Principles and Practice of Radiation Oncology. 5th ed. Philadelphia: Lippincott Williams & Wilkins. 2008. p. 1079.

5.      Stella GM, Luisetti M, Pozzi E, Comoglio PM. Oncogenes in non-small cell lung cancer: emerging connections and novel therapeutic dynamics. Lancet Respir Med. 2013;1:251-61.

6.      Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin/paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947-57.

7.      Cohen MH, Williams GA, Sridhara R, Chen G, Pazdur R. FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. Oncologist. 2003;8:303-6.

8.      Tanaka T, Munshi A, Brooks C, Liu J, Hobbs ML, Meyn RE. Gefitinib radiosensitizes non-small cell lung cancer cells by suppressing cellular DNA repair capacity. Clin Cancer Res. 2008;14(4):1266-73.

9.      Finberg KE, Sequist LV, Joshi VA, Muzikansky A, Miller JM, Han M, et al. Mucinous differentiation correlates with absence of EGFR mutation and presence of KRAS mutation in lung adenocarcinomas with bronchioloalveolar features. J Mol Diagn. 2007;9:320-6.

10.  Majumdar. Stem cells and cancer. Online-Ausg. ed. New York: Springer. 2009. p.193.

11.  Iyer S, Roughley A, Rider A. The symptom burden of non-small cell lung cancer in USA. Support Care Cancer. 2014;22:181-7.

12.  Reinfuss M, Mucha-Maecka A, Walaswk T, Blecharz P, Jakubowicz J, Skotnicki P, et al. Palliative thoracic radiotherapy in non-small cell lung cancer. An analysis of 1250 patients. Palliation of symptoms, tolerance and toxicity. Lung Cancer. 2011;71:344-9.

13.  Sau S, Sau S, Dutta P, Gayen GC, Banerjee S, Basu A. A comparative study of different dose fractionations schedule of thoracic radiotherapy for pain palliation and health-related quality of life in metastatic NSCLC. Lung India : Official Organ of Indian Chest Society. 2014;31:348-53.

14.  Wang J, Xia TY, Wang YJ, Li HQ, Li P, Wang JD, et al. Prospective study of epidermal growth factor receptor tyrosine kinase inhibitors concurrent with individualized radiotherapy for patients with locally advanced or metastatic non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2011;81:59-65.

15.  Laporte S, Squifflet P, Baroux N, Fossella F, Georgoulias V, Pujol J, et al. Prediction of survival benefits from progression-free survival benefits in advanced non-small-cell lung cancer: evidence from a meta-analysis of 2334 patients from 5 randomised trials. BMJ Open. 2013;3(3):e001802.

16.  Imperatori A, La Salvia D, Rotolo N, Nardecchia E, Bandera M, Toungoussova O, et al. Five-year survival of stage IIIA-IIIB (non-N3) non-small cell lung cancer patients after platinum/gemcitabine induction chemotherapy and surgery. J Chemother. 2010;22:191-6.

17.  Dharma-Werdene M, Au HJ, Hanson J, Dupere D, Hewitt J, Feeny D. Baseline FACT-G score is a predictor of survival for advanced lung cancer. Qual Life Res. 2004;13:1209-16.

Corresponding Author

Dr Vikas Verma

Junior Resident, Department of Radiotherapy, Post-graduate institute of medical sciences, Rohtak (INDIA).

Mobile: +91-9050902027, Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Postal address: #805/12, Professor Colony, Kurukshetra, Haryana (INDIA) – 136118