Locally advanced cervical cancer – neoadjuvant chemotherapy followed by concurrent chemoradiation and targeted therapy as maintenance: A phase II study

Aim: The survival in locally advanced cervical cancer remains low. We evaluated the role of neoadjuvant chemotherapy (NACT), chemoradiotherapy (CRT), followed by gefitinib maintenance in locally advanced cervical cancer. Materials and Methods: Twenty-five patients with locally advanced carcinoma cervix were enrolled between July 2012 and May 2013. Patients received 6 weekly doses of NACT Paclitaxel (60 mg/m2) and carboplatin (AUC 2), followed by CRT and brachytherapy. The analysis of epidermal growth factor receptor (EGFR) expression was carried out by immunohistochemistry. Gefitinib (250 mg daily) was given as maintenance therapy for 1 year after completion of chemoradiation. Comparison of EGFR expression and survival outcomes was done. Results: Twenty-four of 25 patients completed the neoadjuvant chemotherapy and concurrent chemoradiotherapy. Post-CRT, all patients were started on gefitinib maintenance, and twenty patients completed the intended 1 year of gefitinib maintenance. Nineteen (76%) patients had a radiological complete response to NACT. EGFR was moderately or strongly expressed in 86.3% of the patients. The 3-year overall survival was 69.8%, and 3-year progression-free survival was 51.4%. Expression of EGFR was not found to be a significant factor affecting overall survival or progression-free survival. Conclusions: Weekly neoadjuvant chemotherapy is associated with a good response rate in locally advanced cervical cancer. Neoadjuvant chemotherapy, chemoradiation, followed by gefitinib maintenance gives good survival outcome in patients with locally advanced cervical cancer.

Evaluation of epidermal growth factor receptor mutations based on mutation specific immunohistochemistry in non-small cell lung cancer: A preliminary study.

Background & objectives: Studies have shown that immunohistochemical (IHC) staining using epidermal growth factor receptor (EGFR) mutation specific antibodies, is an easy and cost-effective, screening method compared with molecular techniques. The purpose of present study was to assess the percentage positivity of IHC using EGFR mutation specific antibodies in lung biopsy samples from patients with primary lung adenocarcinoma (ADC). Methods: Two hundred and six biopsies of primary lung ADC were subjected to EGFR mutation specific antibodies against del E746-A750 and L858R. Detection of EGFR mutation done by high resolution melting analysis (HRM) was used as gold standard. A concordance was established between molecular and IHC results. Frequency of IHC positivity was assessed. Results: Of the 206 patients, 129 were male and 77 were female patients, with a mean age of 54.1 yr. Fifty five (26.6%) patients (36 men; 19 women) showed positivity for IHC of del E746-A750 (33) and L858R (22). HRM results were available in 14 patients which showed EGFR mutations in correspondence with del E746-750 or L858R in 64.2 per cent cases. Positive cases on HRM were further confirmed by DNA sequencing and fragment analysis. Three patients showed exon20 variation. Two cases were negative for mutation. The genotype of del E746-750 mutation was more common than L858R. A concordance was established between molecular mutation and IHC in 85.7 per cent cases. Interpretation & conclusions: In this preliminary study from India mutation specific IHC was used for assessment of mutation status of EGFR. Although the number tested was small, a good concordance was observed between molecular EGFR mutation and IHC expression. IHC methodology is a potentially useful tool to guide clinicians for personalized treatment in lung ADC, especially where facilities for molecular analysis are not readily available and for use in small biopsies where material is scant for molecular tests.