Oral Epidermal Growth Factor Receptor Research Articles

Higher Dose Icotinib in Treating Non-Small Cell Lung Cancer Patients Who Progressed with Conventional Dose of Icotinib

ABSTRACT Aim: Icotinib is an oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for treating non- small-cell lung cancer (NSCLC). Icotinib showed non-inferior efficacy to gefitinib in the phase III ICOGEN study, and improved efficacy was seen as the dose of icotinib increased in the phase I study. The present study was aimed to explore the safety and efficacy of higher dose icotinib (250 mg or 375 mg three times per day) in treating patients who failed with normal dose icotinib. Methods: Patients who progressed (according to RECIST version 1.1) after conventional dose of icotinib (125mg tid) were administered with icotinib 250mg tid, until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), secondary endpoints include objective response rates (ORR), disease control rates (DCR) and safety. This study was registered on the clinicaltrial.gov with an ID of NCT01465243. Results: A total of 29 patients were enrolled in this study, most patients were with stage IV disease (26/29), ECOG score 0-1 (29/29), adenocarcinoma (26/29) and non-smokers (18/29). All patients received icotinib 125 mg tid before progression with a median PFS of 4.4 months (3.4-6.7 months), and then received icotinib 250 mg tid. A total of 29 patients were evaluable for tumour response. The median PFS for 250 mg-treatment stage was 2.1 months (95%CI 1.1-3.1 months). Six patients received icotinib of 375mg tid after progression with icotinib of 250 mg tid, for whom the median PFS was 2.4 months (95%CI 1.1-3.9 months). The ORR and DCR were 6.9% (2/29) and 58.6% (17/29) respectively. Patients with over-three-months PFS when treated with 125mg icotinib have more benefits when treated with 250mg icotinib, compared with patients with PFS less-than-three months (3.0 vs 1.4 months, long-rank P = 0.0093). 51.9% of patients suffered drug-related adverse events (AE), and 1 serious adverse event (urinary tract infection) was reported. The most frequent AEs were rash and diarrhea, with incidence of 25.9% and 11.1%, respectively. No ILD or treatment-related death was reported. Conclusions: Icotinib was well tolerated with 250 mg tid or 375 mg tid. NSCLC patients continued to benefit from higher dose icotinib after progression with routine dose, especially in patients with a median PFS exceeding 3 months at the 125 mg dose level. Disclosure: X. Yuan is a salaried employee of Betta Pharma Inc., no other potential conflict of interest relevant to this article was reported. X. Yuan worked as assistant of Xiaoqing Liu for study directing in this study, and was involved in writing and revision of this abstract. All authors have declared no conflicts of interest.

Oral epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer: comparative pharmacokinetics and drug-drug interactions.

The development of orally active small molecule inhibitors of the epidermal growth factor receptor (EGFR) has led to new treatment options for non-small cell lung cancer (NSCLC). Patients with activating mutations of the EGFR gene show sensitivity to, and clinical benefit from, treatment with EGFR tyrosine kinase inhibitors (EGFR-TKls). First generation reversible ATP-competitive EGFR-TKls, gefitinib and erlotinib, are effective as first, second-line or maintenance therapy. Despite initial benefit, most patients develop resistance within a year, 50-60% of cases being related to the appearance of a T790M gatekeeper mutation. Newer, irreversible EGFR-TKls - afatinib and dacomitinib - covalently bind to and inhibit multiple receptors in the ErbB family (EGFR, HER2 and HER4). These agents have been mainly evaluated for first-line treatment but also in the setting of acquired resistance to first-generation EGFR-TKls. Afatinib is the first ErbB family blocker approved for patients with NSCLC with activating EGFR mutations; dacomitinib is in late stage clinical development. Mutant-selective EGFR inhibitors (AZD9291, CO-1686, HM61713) that specifically target the T790M resistance mutation are in early development. The EGFR-TKIs differ in their spectrum of target kinases, reversibility of binding to EGFR receptor, pharmacokinetics and potential for drug-drug interactions, as discussed in this review. For the clinician, these differences are relevant in the setting of polymedicated patients with NSCLC, as well as from the perspective of innovative anticancer drug combination strategies.

Metabolite Characterization of Anti-cancer Agent Gefitinib in Human Hepatocytes

Intensive Biotransformation studies on Gefitinib could play a significant role in designing and synthesizing new drugs around the core structure of Gefitinib. These studies may be useful in developing an entirely new drug by blocking the metabolic spots in Gefitinib. Gefitinib (Iressa) was the first oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Gefitinib shows toxicity to cancer cells and has the capability to inhibit the growth of cancer cells. Gefitinib is considered as one of the selective EGFR inhibitors to be available in clinical practice. In 2003, FDA had approved Gefitinib for metastatic non-small-cell lung cancer therapy (NSCLC). However, it was observed that NSCLC Patients who responded to treatment developed resistance to Gefitinib. Hence, in the present study Gefitinib was incubated with hepatocytes to identify both phase-I and Phase-II metabolites. Identified Phase -I metabolites were due to oxidative defluorination, N-dealkylation and loss of morpholine ring. One of the phase-II metabolites identified i.e. the glutathione adduct suggests the need to modify the structure of the drug for higher potency and safety.

Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer.

Past studies have demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors can significantly improve clinical outcomes in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and sensitive EGFR gene mutations. Gefitinib (Iressa®), the first oral EGFR tyrosine kinase inhibitor, has been shown to be more effective and better tolerated than chemotherapy either in first-line or second-line treatment for patients with advanced NSCLC harboring sensitive EGFR mutations. Conversely, among patients with wild-type EGFR, gefitinib is inferior to standard chemotherapy in both the first-line and second-line settings. Further, gefitinib is effective in patients with brain metastases because of its low molecular weight and excellent penetration of the blood–brain barrier. In this review, we summarize the current data from clinical trials with gefitinib and appraise its role in the management of locally advanced or metastatic NSCLC.

Effects of icotinib on advanced non-small cell lung cancer with different EGFR phenotypes.

Icotinib is the first oral epidermal growth factor receptor (EGFR) tyrosine kinase receptor inhibitor, which has been proven to exert significant inhibitory effects on non-small cell lung cancer in vitro. Clinical evidence has showed that the efficacy of Icotinib on retreating advanced non-small cell lung cancer is comparable to Gefitinib. However, different phenotypes of EGFR can affect the therapeutic outcomes of EGFR tyrosine kinase receptor inhibitor. Therefore, our study focused on efficacy and safety of Icotinib in patients with advanced non-small cell lung cancer of different EGPR phenotypes. Clinical data of patients with advanced non-small cell lung cancer who received Icotinib treatment from August, 2011 to May, 2013 were retrospectively analyzed. Kaplan-Meier analysis was used for survival analysis and comparison. 18 wild-type EGFR and 51 mutant type were found in a total of 69 patients. Objective response rate of patients with mutant type EGFR was 54.9 % and disease control rate was 86.3 %. Objective response rate of wild-type patients was 11.1 % (P = 0.0013 vs mutant type), disease control rate was 50.0 % (P = 0.0017). Median progression-free survival (PFS) of mutant type and wild-type patients were 9.7 and 2.6 months, respectively (P < 0.001). Median PFS of exon 19 mutated mutant patients was 11.3 months, mean PFS of exon 21 L858R mutated mutant patients was 8.7 months (P = 0.3145). Median overall survival (OS) of EGFR mutated patients had not reached. OS time of 13 wild-type patients was 12.9 months (P < 0.001). The common adverse reactions of Icotinib included rash, diarrhea, itching skin with occurrence rates of 24.6 % (17/69), 13.0 % (9/69), and 11.6 % (8/69), respectively. Most adverse reactions were grade I-II. Icotinib has great efficacy in EGFR mutated patients, making it an optimal regimen to treat EGFR mutated patients. Furthermore, most of adverse reactions associated with Icotinib treatment were tolerable.

Tilting the Balance of Dose Modification for Oral Anticancer Drugs?

Tilting the Balance of Dose Modification for Oral Anticancer Drugs?

Surviving with lung cancer: Medication-taking and oral targeted therapy

Oral epidermal growth factor receptor inhibitors (EGFRIs) improve survival for non-small cell lung cancer (NSCLC) patients; however, medication-taking implications are unknown. We used grounded theory to explore the process of medication-taking for NSCLC patients receiving oral EGFRIs. Thirty-two interviews were conducted for 13 participants purposively selected for gender, race/ethnicity, age, time in therapy, dose reductions, and therapy discontinuation and theoretically sampled for age and health insurance carrier. The study produced a grounded theory, Surviving with Lung Cancer, in which participants framed EGFRI therapy within recognition of NSCLC as a life-limiting illness without cure. Medication-taking was a “window” into participants' process of surviving with metastatic cancer that included deciding and preparing to take EGFRIs and treating lung cancer as a chronic condition. Our results contribute to understanding how NSCLC patients view themselves in the context of a life-limiting illness and support development of a theoretically-based intervention to improve medication-taking with EGFRIs.

Clinical pharmacokinetics of Icotinib, an anti-cancer drug: evaluation of dose proportionality, food effect, and tolerability in healthy subjects

Icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, has proved effectiveness in xenografted nude mice. Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time, including dose proportionality, food effect, and tolerability. Two studies were conducted in total of 22 healthy subjects: a randomized, two-Latin-square crossover, dose proportional study (n = 12) and a randomized two-way crossover food-effect study (n = 10). Plasma concentration of Icotinib reached peak at a median Tmax of 0.75-3.5 h after single dose and then declined with a mean t1/2β of 6.02-7.83 h. Over the dose range of 100-600 mg, AUC values were proportional to dose and Cmax showed a slight saturation when dose increases. Only 0.2 % of the dose was excreted through kidney in unchanged Icotinib. After dosing 400 mg of Icotinib with high-fat and high-calorie meal, mean Cmax and AUC were significantly increased by 59 and 79 %, respectively. Three subjects experienced four adverse events (rash, increase in AST and ALT, and external injury). Rash and increased levels of AST and ALT were considered as drug-related. No serious adverse events were reported. The current work demonstrated that Icotinib was well tolerated in healthy male subjects (n = 22) over the dose range of 100-600 mg with or without food. Icotinib exposure, expressed in AUC, was proportionally increased with dose over the above dose range. Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects.

Efficacy and safety of icotinib in Chinese patients with advanced nonsmall cell lung cancer after failure of chemotherapy

Background The preclinical experiments and several clinical studies showed icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in Chinese patients with advanced non-small cell lung cancer (NSCLC) who failed previous chemotherapy. We performed a retrospective study of the efficacy and safety of icotinib monotherapy in a different and more recent sample of Chinese patients. Methods The clinical data of 149 patients with advanced NSCLC who were admitted to Zhejiang Cancer Hospital from August 1, 2011 to July 31, 2012 were retrospectively analyzed. All patients were given icotinib treatment after the failure of previous chemotherapy. Univariate and multivariate analyses were conducted based on the Kaplan Meier method and Cox proportional hazards model. Results The objective response rate was 33/149 and disease control rate was 105/149. No complete response occurred. Median progression free survival (PFS) with icotinib treatment was 5.03 months (95% CI: 3.51 to 6.55). Median overall survival was 12.3 months (95% CI: 10.68 to 13.92). Multivariate analysis showed that the mutation of EGFR and one regimen of prior chemotherapy were significantly associated with longer PFS. At least one drug related adverse event was observed in 65.8% (98/149) of patients, but mostly grade 1 or 2 and reversible and none grade 4 toxicity. Conclusions Icotinib monotherapy is an effective and well tolerated regimen for Chinese patients with NSCLC after the failure of chemotherapy. It is a promising agent and further study with icotinib in properly conducted trials with larger patient samples and other ethnic groups is warranted.

Risk of interstitial lung disease with gefitinib and erlotinib in advanced non-small cell lung cancer: A systematic review and meta-analysis of clinical trials

ObjectivesGefitinib and erlotinib are oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) widely used in advanced non-small cell lung cancer (NSCLC). Interstitial lung disease (ILD) events have been described with these agents, although the overall risk remains unclear. We performed a systematic review and meta-analysis to determine the incidence and the relative risk (RR) associated with the use of gefitinib and erlotinib. Materials and methodsPubMed databases were searched for articles published from January 2000 to October 2012, and abstracts presented at the American Society of Clinical Oncology and the European Society of Medical Oncology meetings held between 2000 and 2012 were searched for relevant studies. Eligible studies included randomized controlled trials with gefitinib and erlotinib in advanced NSCLC patients. Summary incidence rates, relative risks, and 95% CIs were calculated using fixed-effects or random-effects models, depending on the heterogeneity of the included studies. Results15,618 patients from 29 randomized controlled trials were selected for this meta-analysis. The overall incidence for all-grade ILD events was 1.2% (95% CI, 0.9–1.6%) among patients receiving gefitinib and erlotinib, with a mortality of 22.8% (95% CI, 14.6–31.0%). Compared with controls, the RR of all-grade ILD events associated with gefitinib and erlotinib was 1.53 (95% CI, 1.13–2.08; P=0.006) using a fixed-effects model. The RR of fatal ILD events associated with EGFR TKIs treatment was 1.96 (95% CI, 1.03–3.72, P=0.041) compared with control patients. The analysis was also stratified for drug type, study location, treatment arm, and treatment line, but no significant differences in RRs were observed. ConclusionTreatment with EGFR TKIs gefitinib and erlotinib is associated with a significant increase in the risk of developing both all-grade and fatal ILD events in advanced NSCLC.

Is there an interaction between epidermal growth factor receptor (EGFR) inhibition and p16-status in patients (pts) with oropharyngeal squamous cell cancer: A retrospective analysis.

6061 Background: Conflicting data exists about whether EGFR inhibition is more or less effective in pts with p16 positive or negative oropharynx cancer (OPC). We update results from two institutional clinical trials in pts with locoregionally advanced head and neck squamous cell carcinoma (LRA HNSCC) given chemoradiotherapy either with or without the oral EGFR inhibitor gefitinib (G), with specific attention to the subset of pts with p16-defined OPC. Methods: Between 1996-2000, 44 pts with LRA HNSCC were treated on a Cleveland Clinic IRB-approved protocol using concurrent cisplatin, fluorouracil and radiation without G (G- cohort). Between 2003-2007, 60 similar pts were treated using the same chemoradiotherapy regimen with the addition of G 250 mg daily for 2 years beginning on day 1 of radiation (G+ cohort). Available biopsy material from 64 OPC pts (23 G-, 41 G+) was retrieved and tested by immunohistochemistry for p16 (as a surrogate for human papillomavirus) positivity. Kaplan-Meier outcome projections were compared using the log-rank test. Results: With a median follow-up in excess of 7 years for all pts, survival and patterns of failure did not differ between the two trials. The 5-year overall survivals (OS) were 68% vs. 64% (p=0.73) and relapse-free survivals (RFS) 65% vs. 63% (p=0.85) in the G+ and G- cohorts respectively. OPC was more frequent in the more recently treated G+ cohort (68% vs. 53%). Excluding 14 pts for whom tumor was unavailable, OPC p16-positivity was also more frequent in the G+ cohort (74% vs. 63%). As expected, outcomes in the p16+ OPC pts were significantly better than in the p16- OPC pts including OS (66% vs. 58%, p=0.049) and RFS (69% vs. 56% p=0.027). However, in comparing the G+ and G- cohorts, the use of G did not significantly alter any survival outcome or pattern of failure in either the p16+ or p16- OPC pts. Conclusions: Although the retrospective nature of this analysis limits the strength of our conclusions, in the definitive management of LRA HNSCC, we could identify no effect of oral EGFR inhibition on any outcome. In subset analysis there was also no differential impact found in either the p16+ or p16- OPC pts. Clinical trial information: NCT00352105.

Phase I study of the safety and pharmacokinetics of epitinib, an oral EGFR tyrosine kinase inhibitor, in patients with advanced solid tumors.

e19042 Background: Epitinib is an oral small molecule compound selectively inhibits epidermal growth factor receptor (EGFR). It has demonstrated potent inhibitory effects on multiple human tumor xenografts with a large safety window and broad tissue distribution including high drug contribution in brain. This first-in-human study is being conducted to assess the safety and tolerability, pharmacokinetics (PK), and preliminary anti-tumor activity of Epitinib. Methods: This phase I study uses a 3+3 design for dose-escalation of Epitinib given once daily (QD) in 28-day treatment cycles in patients with solid tumors who failed or have no access to standard therapies. Safety and tumor response are assessed according to NCI CTCAE 4.0 and RECIST 1.1, respectively. Results: By Dec 31, 2012, 19 pts aged 40-66 yr old (ECOG PS 1) with NSCLC (n=16) or breast cancer (n=3) were enrolled in 5 dose cohorts of 20-160 mg. Six NSCLC pts had EGFR mutations (3 with T790M). All pts had ≥2 lines of prior systemic treatments (7 pts with gefitinib or elotinib). Most AEs were mild (Gr1). Treatment-related AEs included skin rash (36.8%), abnormal liver function tests (42.1%), diarrhea (10.5%), vomiting (5.3%), paronychia (5.3%), decreased neutrophil count (5.3%) and increased creatinine (5.3%). Three SAEs were reported as possibly unrelated to the study drug. No DLT was observed and MTD has not been reached yet. PK analysis showed that the mean elimination half-life of Epitinib was approximately 40 hours and Tmax was around 2 h. Both Cmaxand AUC exhibited good dose proportionality over the studied dose range with low inter-patient variability following single and multiple doses. Among 15 evaluable pts, 1 EGFR mutation+ NSCLC pt achieved confirmed partial response (66.7% tumor reduction) for more than 6 months and the treatment is ongoing; 8 pts had stable disease, including 1 with T790M for 6 months and 1 with brain metastasis for 12 months who is still on treatment. Conclusions: Epitinib was well tolerated at doses up to 160mg QD to date with manageable adverse events and excellent pharmacokinetic properties. Encouraging clinical activity was observed, including durable SD in NSCLC patients with T790M or brain mets.

PHC-012 Erlotinib in Non-Small Cell Lung Cancer Patients from Fernando Fonseca Hospital

BackgroundThe oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib is an established second-line treatment for advanced non-small cell lung cancer (NSCLC). Erlotinib delays disease progression and increases...

Afatinib: emerging next-generation tyrosine kinase inhibitor for NSCLC

The discovery of epidermal growth-factor receptor (EGFR)-activating mutations and the introduction of oral EGFR tyrosine kinase inhibitors (EGFR-TKIs) have expanded the treatment options for patients with non-small cell lung cancer. The first two reversible EGFR-TKIs, erlotinib and gefitinib, are approved for use in the first-line setting in patients with known EGFR-activating mutations and in the second- and third-line settings for all NSCLC patients. These first-generation EGFR-TKIs improve progression-free survival when compared to chemotherapy in patients with EGFR-activating mutations in the first-line setting. However, nearly all patients develop resistance to EGFR-directed agents. There is a need for further therapy options for patients with disease progression after treatment with reversible EGFR-TKIs. Afatinib is an irreversible ErbB family blocker that inhibits EGFR, HER2, and HER4. In vitro and in vivo, afatinib have shown increased inhibition of the common EGFR-activating mutations as well as the T790M resistance mutation when compared to erlotinib and gefitinib. Clinically, afatinib has been evaluated in the LUX-Lung series of trials, with improvement in progression-free survival reported in patients with EGFR-activating mutations in both first- and second-/third-line settings when compared to chemotherapy. Further investigation is needed to determine the precise role that afatinib will play in the treatment of patients with non-small cell lung cancer and EGFR-activating mutations.

Four cases of interstitial lung disease induced by erlotinib and a review of the literatures

厄洛替尼是一种口服表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitor, EGFR-TKI），广泛应用于晚期非小细胞肺癌的治疗。尽管目前认为这类药物安全性良好，但可诱发严重的间质性肺病（interstitial lung disease, ILD）。文献中对吉非替尼所致ILD的报道较多，而对厄洛替尼所致的ILD报道较少。现报道上海市肺科医院4例厄洛替尼所致ILD，并复习相关文献，以使临床医生提高警惕。监测正在服用厄洛替尼患者的肺部症状、体征，做到及时诊断、尽早治疗对于厄洛替尼所致ILD的预后尤为重要。

New EGFR-TKI: A case report of recurrent lung adenocarcinoma successfully treated with icotinib

Icotinib is a new oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). We report on a 49-year-old man with recurrent lung adenocarcinoma treated with icotinib. The patient obtained a partial remission in 4 weeks that was maintained 14 months. Retrospective examination of EGFR mutations confirmed he had a sensitive mutation (exon 19 deletion). This case supports that icotinib has great efficacy in advanced non-small cell lung cancer with sensitive EGFR mutations.

Sorafenib and continued erlotinib or sorafenib alone in patients with advanced non-small cell lung cancer progressing on erlotinib: A randomized phase II study of the Sarah Cannon Research Institute (SCRI).

7587 Background: Erlotinib is an oral epidermal growth factor receptor kinase inhibitor used in the treatment of advanced non-small-cell lung cancer (NSCLC). Resistance develops in patients (pts) who initially respond to erlotinib leading to progressive disease (PD). Sorafenib is an oral inhibitor of vascular endothelial and platelet-derived growth factor receptors and Raf kinases which play important roles in PD. This randomized phase II study evaluated the role of sorafenib and continued erlotinib or sorafenib alone in pts with progressive NSCLC following initial benefit with erlotinib. Methods: Eligible pts had IIIB/IV NSCLC, an ECOG PS 0-2, and had received ≤2 lines of therapy with the last being single-agent erlotinib. Pts must have PD following clinical benefit (complete/partial response/stable disease) from erlotinib for &gt;8 weeks. Pts were randomized 1:1 to continue erlotinib at the dose administered at the time of PD with the addition of sorafenib 400 mg orally twice daily (Arm A) or to sorafenib alone (Arm B). Cycles were 28 days with restaging every 2 cycles. The primary endpoint was progression-free survival (PFS). Results: 52 pts were enrolled from 2/2008 to 3/2011 (A 24; B 28). Baseline characteristics were balanced between arms and included: median age 65 years (41-87); 65% female; 69% adenocarcinoma/large cell; and 96% PS &lt;2. 41% of pts were either never smokers or smoked &lt;100 cigarettes/lifetime. Pts received a median of 8 weeks of treatment per arm (0.6–67 weeks). The median PFS was 3.1 (95% CI 1.7-3.7) and 2.3 (1.7-3.6) months for A and B, respectively (p=.84). There were no grade 3/4 hematologic toxicities in either arm except grade 3 anemia in 1 pt (A). Severe nonhematologic toxicities in &gt;5% included: fatigue 17%(A)/7%(B); diarrhea 17%/0; dehydration 13%/7%; hand-foot skin reaction 8%/8%, and anorexia 4%/7%. Conclusions: Sorafenib has modest activity when used in combination with erlotinib or as a single agent in pts with PD following benefit with erlotinib alone. Additional study to identify potential subsets of refractory pts who might derive the greatest benefit from sorafenib are warranted.

Long-Term Remission After Gefitinib Therapy in an Elderly Patient With Advanced Non-Small-Cell Lung Carcinoma

The prognosis for non-small-cell lung carcinoma (NSCLC) pat ients in advanced stages is poor. Gefitinib inhibits the tyrosine kinase activity of epidermal growth factor receptor (EGFR) and have been studied extensively. Oral epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been as the 2nd-line treatment for NSCLC. It is widely accepted that some clinicopathologic characteristics (female, nonsmoking status, Asian, and EGFR mutations) are the main clinical positive predictive factors when using EGFR-TKIs. The el der patients often suffer from deterioration of performance status (PS). The side reaction caused by chemotherapy is serious and unavoidable. For the elder patients with positive predictive factors and poor PS, there is no report about anti-NSCLC using gefitinib as the 1st-line treatment. We report the case of an 84-year-old woman with diffuse bone metastases from lung cancer. She received oral gefitinib 150 mg / day, combined with three dimensional conformal radiation therapies (3DCRT). A total tumor dose of 36Gy / 12fractions was delivered to the tumor bed and localized metastatic bone pain areas, respectively. After concurrent gefitinib-3DCRT, gefitinib was continued as maintenance therapy. She experienced total regression of the metastases under gefitinib treatment for 30 months. Gefitinib therapy provided effective anti-tumor results. Therefore, for NSCLC patients of multiple metastases with favorable predictive factors such as EGFR mutations, adenocarcinoma, Asian, female gender and nonsmoking status, we suggest that gefitinib may become the 1st-line treatment even with poor PS. doi:10.4021/jmc513w

Long-Term Remission After Gefitinib Therapy in an Elderly Patient With Advanced Non-Small-Cell Lung Carcinoma

The prognosis for non-small-cell lung carcinoma (NSCLC) patients in advanced stages is poor. Gefitinib inhibits the tyrosine kinase activity of epidermal growth factor receptor (EGFR) and have been studied extensively. Oral epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been as the 2nd-line treatment for NSCLC. It is widely accepted that some clinicopathologic characteristics (female, nonsmoking status, Asian, and EGFR mutations) are the main clinical positive predictive factors when using EGFR-TKIs. The elder patients often suffer from deterioration of performance status (PS). The side reaction caused by chemotherapy is serious and unavoidable. For the elder patients with positive predictive factors and poor PS, there is no report about anti-NSCLC using gefitinib as the 1st-line treatment. We report the case of an 84-year-old woman with diffuse bone metastases from lung cancer. She received oral gefitinib 150 mg/day, combined with three dimensional conformal radiation therapies (3DCRT). A total tumor dose of 36Gy/12fractions was delivered to the tumor bed and localized metastatic bone pain areas, respectively. After concurrent gefitinib-3DCRT, gefitinib was continued as maintenance therapy. She experienced total regression of the metastases under gefitinib treatment for 30 months. Gefitinib therapy provided effective anti-tumor results. Therefore, for NSCLC patients of multiple metastases with favorable predictive factors such as EGFR mutations, adenocarcinoma, Asian, female gender and nonsmoking status, we suggest that gefitinib may become the 1st-line treatment even with poor PS. J Med Cases. 2012;3(2):140-143 doi: https://doi.org/10.4021/jmc513w

Single‐arm phase II study of multiagent concurrent chemoradiotherapy and gefitinib in locoregionally advanced squamous cell carcinoma of the head and neck

This phase II study tested the addition of the oral epidermal growth factor receptor gefitinib to multiagent concurrent chemoradiotherapy regimen in head and neck squamous cell cancer (HNSCC). Patients with stage III-IV HNSCC received hyperfractionated radiation (72-74.4 Gy at 120 cGy twice daily), with concurrent 96-hour infusions of cisplatin 20 mg/m(2) /day and fluorouracil 1000 mg/m(2) /day given during weeks 1 and 4. Daily gefitinib 250 mg was started on day 1 of radiation and continued for 2 years. Results were retrospectively compared with our previous study using identical chemoradiotherapy without gefitinib. Sixty patients were enrolled in the study; 80% had stage IV disease and 68% had oropharyngeal primary tumors. The full course of gefitinib was not tolerated by 42%; there were 5 treatment-related deaths (8%). With a median follow-up of 54 months, 2- and 3-year overall survival estimates were 80% and 71%, respectively. Projected distant metastatic control at 2 and 3 years was 88%. When compared with our historical cohort, acute toxicities including renal dysfunction and unplanned rehospitalization were worse in the study patients. Projected outcome estimates did not differ between the 2 cohorts. Addition of gefitinib to concurrent chemoradiotherapy was difficult to complete, did not improve outcomes, and increased toxicity.