Abstract
Purpose: The purpose was to compare feasibility, tolerability, toxicity and local control of concomitant chemoradiation with weekly cisplatin and erlotinib versus concomitant chemoradiation with weekly cisplatin in EGFR positive locally advanced carcinoma cervix.
Material and Methods: In this prospective, comparative study, 60 histopathologically proven locally advanced carcinoma cervix patients with EGFR positivity received either Erlotinib (150 mg/day) with concomitant chemoradiation (study group) or CCRT (control group). Treatment with CCRT included cisplatin 40 mg/m2 intravenously weekly concurrently with external beam radiation(50 Gy in 25 fractions over 5 weeks) followed by intracavitary HDR brachytherapy (7Gy to point A three times, once in a week). Tumor response was calculated as per the WHO criteria. The treatment induced toxicity such as anaemia, leucopenia and nausea/vomiting were graded as per WHO criteria. Skin reaction, diarrhea and genioturinary toxicity were graded as per RTOG criteria.
Results: Overall, complete response was seen in 93% in study group and 86% in control group at the end of treatment. In stage IIB and IIIA, complete response was observed in 100% of patients in the study and control group. Sixty percent patients with stage IIIB in study group and control group had complete response. Forty percent patients with stage IIIB in two groups showed partial response. At last follow up, 93% patients in study group and 80% patients in control group were observed to be free of disease. There were 7% and 10% patients with residual disease in study group and control group respectively. Distant recurrence was seen in 10% patients in control group. Even though response was better in study group but the difference in two groups was not statistically significant.
The toxicities commonly encountered in both the treatment groups were majority of Grade I/II. A higher incidence of nausea, vomiting, diarrhea and skin rash was noted in the Erlotinib plus CCRT group in comparison CRT. No Grades 4 and 5 toxicity was observed in Erlotinib with CCRT. Erlotinib was observed to be safe with manageable toxicity profile.
Conclusion: Addition of Erlotinib to standard cisplatin-based CCRT showed improved tumor response in comparison to cisplatin-based CRT alone in treatment of locally advanced carcinoma cervix, although not statistically significant with manageable toxicity.
Keywords: Advanced, Carcinoma, Cervix, Epidermal growth factor receptor, Erlotinib, Tyrosine kinase inhibitor
References
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68: 394-424.
- Ferlay J, Soeriomataram I, Ervik M, Dikshit R, Esre S, Mathers C, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):359-86.
- Quinn MA, Benedet JL, Odicino F. Carcinoma of the cervix uteri. FIGO 6th Annual Report on the Results of Treatment in Gynaecological Cancer. Int J Gynaecol Obstet.2006; 95:43-103.
- Eifel PJ, Berek JS, Markman MA. Cancer of cervix, vagina and vulva. In: Devita VT, Lawerence TS, Rosenberg SA, editors. Cancer principles and practice of oncology. 10th Philadelphia: Lippincotts Williams and Wilkins; 2015. 1311-44.
- Pearcey R, Miao Q, Kong W. Impact of adoption of chemoradiotherapy in the outcome of cervical cancer. J ClinOncol. 2007;25:2383-8.
- Halperin EC, Perez CA, Brady LW, editors. Perez and Brady’s Principles and Practice of Radiation Oncology. 6th Uterine cervix. Lippincott Williams & Wilkins. 2012. p. 1355-425.
- Baselga J. New technologies in epidermal growth factor receptor-targeted cancer therapy. Signal 2000;1:12-21.
- Wells A. The epidermal growth factor receptor (EGFR)—a new target in cancer therapy. Signal 2000;1:4-11.
- Brabender J, Danenberg KD, Metzger R et al. Epidermal growth factor receptor and HER2-neu mRNA expression in non-small cell lung cancer is correlated with survival. Clin Cancer Res 2001;7:1850-5.
- Meyers MB, Shen WP, Spengler BA et al. Increased epidermal growth factor receptor in multidrug-resistant human neuroblas-toma cells. J Cell Biochem 1988;38:87-97.
- Wosikowski K, Schuurhuis D, Kops GJ et al. Altered gene expression in drug-resistant human breast cancer cells. Clin Cancer Res 1997;3:2405-14.
- Woodworth CD, Diefendorf LP, Jette DF, Mohammed A, Moses MA, Searleman SA, et al. Inhibition of the epidermal growth factor receptor by erlotinib prevents immortalization of human cervical cells by human papillomavirus Type 16. Virology 2011;421:19-27.
- Nogueira-Rodrigues A, do Carmo CC, Viegas C, Erlich F, Camisão C, Fontão K, et al. PhaseI trial of erlotinib combined with cisplatin and radiotherapy for patients with locally advanced cervical squamous cell cancer. Clin Cancer Res 2008;14:6324-9.
- Nogueira-Rodrigues A, =Moralez G, Grazziotin R, Carmo CC, Small IA, Alves FV, et al. Phase 2 trial of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced cervical cancer. Cancer 2014;120:1187-93.
- Rawat S, Advait MK, Mandloi P. Comparative Evaluation of Radiotherapy with Concurrent Weekly Cisplatin versus Concurrent Daily Erlotinib and Weekly Cisplatin in Locally Advanced Carcinoma Cervix. Int J of Scientific Study. 2018;5(10).
- Whitney CW, Sause W, Bundy BN. Randomised comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiationtherapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes. J ClinOncol. 1999;17:1339-48.
- Rose PG. Chemoradiotherapy- the new standard care for invasive cancer. Drugs. 2000;60:1239-44.
- Thomas GM. Concurrentchemotherapy and radiation for locally advanced cervical cancer: the new standard of care. Semin Radiat Oncol. 2000;10:44-50.
- Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J ClinOncol. 2007;25:1960-6.
- Shepherd FA, Pereira JR, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123-32.
- Schilder, RJ, Sill MW, Lee YCMannel R. A Phase II trial of erlotinibin recurrent squamous cell carcinoma of the cervix.Int J Gynecol Cancer. 2009;19:5929-33.
Corresponding Author
Dr Jyoti Pannu
Junior Resident, Department of Radiotherapy, Post-graduate Institute of Medical Sciences, Rohtak (INDIA)
Postal address: #1543 Sector 3, Rohtak, Haryana (INDIA)-124001
Mobile: +91-9416763698, Email: This email address is being protected from spambots. You need JavaScript enabled to view it.