Mok et al conducted a large phase iii study that compared gefitinib with carboplatinpaclitaxel in the firstline setting in asian patients who had. Lung adenocarcinoma tends to grow more slowly than other lung cancers. Gefitinib plus chemotherapy versus placebo plus chemotherapy in egfrmutationpositive nonsmallcell lung cancer after progression on firstline gefitinib impress. On the other hand, calgb 30106 trial evaluated concurrent trt and gefitinib with or without weekly paclitaxel plus carboplatin, and 89% of patients were currentheavy smoker. Somatic mutations affect key pathways in lung adenocarcinoma. Gefitinib versus vinorelbine plus cisplatin as adjuvant. What is the role of gefitinib in the treatment of nonsmall. Lung adenocarcinoma is categorized as such by how the cancer cells look under a microscope.
Lung adenocarcinoma is a subtype of nonsmall cell lung cancer nsclc a group of lung cancers that are named for the kinds of cells found in the cancer and how the cells look under a microscope. A randomized phase ii trial that compares paclitaxel carboplatin pc to pc chemotherapy followed by gefitinib for 2 weeks in patients with nsclc without egfr mutations. Therefore, we conducted a phase ii study of gefitinib as a firstline therapy in elderly patients with pulmonary adenocarcinoma. We describe the occurrence and management of metastatic spread of a pulmonary carcinoma to the rectum. This phase ii trial is studying the side effects of giving paclitaxel and carboplatin together with gefitinib and to see how well it works in treating patients with stage iiib or stage iv nonsmall cell lung cancer.
At the final analysis, neither dose of gefitinib improved overall survival when added to paclitaxel and carboplatin compared with paclitaxel and carboplatin plus placebo golrank p. Gefitinib in combination with paclitaxel and carboplatin. When the tca is discontinued, resume gefitinib at 250 mg once daily after 7 days 1. In japan, a randomized study of carboplatin plus nab. Aug 16, 2017 gefitinib or carboplatinpaclitaxel in pulmonary adenocarcinoma. Randomized phase ii study of paclitaxelcarboplatin. Gefitinib or carboplatinpaclitaxel in pulmonary adenocarcinoma article in yearbook of pulmonary disease 2010. Paclitaxelcarboplatin pc followed by gefitinib versus. The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority, as compared with carboplatin paclitaxel, with respect to progressionfree survival. Gefitinib in egfrmutant metastatic nsclc the asco post. Methods eligible patients were 70 years or older, had pulmonary adenocarcinoma, stage iiib or iv disease, an eastern cooperative oncology group performance status of 02 and adequate organ functions. Is gefitinib combined with platinumdoublet chemotherapy a. The epidermal growth factor receptor egfr tyrosine kinase inhibitor gefitinib was initially approved in japan in 2002 for the treatment of advanced or metastatic non. Adjuvant gefitinib led to significantly longer diseasefree survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage iiiiia n1n2 egfrmutant nsclc.
Randomized phase ii study of paclitaxelcarboplatin intercalated with gefitinib compared to paclitaxelcarboplatin alone for chemotherapynaive nonsmall cell lung cancer in a clinically selected population excluding patients with nonsmoking adenocarcinoma or mutated egfr. Pulmonary toxicities of gefitinib in patients with advanced. Withhold iressa and promptly investigate for ild in any patient who presents with worsening of respiratory symptoms such as dyspnea, cough and fever. Intervention after obtaining written informed consent, patients were randomly assigned in a 1. Gefitinib is an anilinoquinazoline with the chemical name 4quinazolinamine, n3chloro4 fluorophenyl7methoxy634morpholin propoxy and the following structural formula. Gefitinib in combination with paclitaxel and carboplatin in. Gefitinib or chemotherapy for nonsmall cell lung cancer with mutated egfr. Egf receptor gene mutations are common in lung cancers from never smokers and are associated with sensitivity of tumors to gefitinib and erlotinib. The american college of chest physicians lung cancer. Further clinical trials are needed to evaluate the role of gefitinib therapy followed by surgical resection. Management of egfr mutationpositive nonsmall cell lung. If the inline pdf is not rendering correctly, you can download the pdf file here. Personalized targeted therapy in advanced nonsmall cell.
Gefitinib iressa is an epidermal growth factor receptor egfr tyrosine kinase inhibitor that offers treatment for patients with locally advanced or metastatic nonsmall cell lung cancer nsclc, in particular in those who are harbouring egfr mutations. Recently, however, advances in lung cancer treatment have improved the chance of longterm survival of patients with unresectable distant metastases. Randomized phase ii trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic nonsmallcell lung cancer. In this phase 3, openlabel study, we randomly assigned previously untreated patients in east asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib 250 mg per day 609 patients or carboplatin at a dose calculated to produce an area under the curve of 5 or 6 mg per. Gefitinib or carboplatin paclitaxel in pulmonary adenocarcinoma. The drug was effective, but with unacceptable toxicity in patients with squamous histology. Bc cancer protocol summary firstfor line treatment of. Withhold iressa and promptly investigate for ild in any patient who presents with worsening of respiratory. Gefitinib was the first egfrtki evaluated in a phase iii trial. While previous studies with cytotoxic agents and gefitinib failed to show any benefit, we altered the schedule of administration in hopes to gain synergy between agents. The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority, as compared with carboplatinpaclitaxel, with respect to progressionfree survival. Induction chemotherapy followed by gefitinib and concurrent. What is the efficacy of gefitinib versus carboplatin.
Gefitinib is superior to carboplatinpaclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in east asia. Therefore, it is only effective in cancers with mutated and overactive egfr. The 12month progression free rate of gefitinib compared with chemotherapy was found to be significantly better 25% vs. Nov 09, 2016 the epidermal growth factor receptor egfr tyrosine kinase inhibitor gefitinib was initially approved in japan in 2002 for the treatment of advanced or metastatic non. Similarly, the hr of gefitinib compared with carboplatin plus paclitaxel for progressionfree survival in patients with egfr mutations was 036 in the study done by the north east japan nej 002 gefitinib study group, which was presented at the annual meeting of the american society of clinical oncology orlando, fl, usa, may 29june 2. Firstline gefitinib in caucasian egfr mutationpositive nsclc patients. Phase iii study of gefitinib or pemetrexed with carboplatin. Arm a was selected for a subsequent phase iii study. Mok et al conducted a large phase iii study that compared gefitinib with carboplatin paclitaxel in the firstline setting in asian patients who had adenocarcinoma and had never smoked or were. Paclitaxel, carboplatin, and gefitinib in treating patients. A randomized phase ii trial that compares paclitaxelcarboplatin pc to pc chemotherapy followed by gefitinib for 2 weeks in patients with nsclc without egfr mutations.
In a large phase iii trial ipass in chemotherapynaive asian patients with adenocarcinoma who were never smokers or former light. Firstline therapy with gefitinib prolongs progressionfree survival and improves quality of life among selected patients with nonsmall cell lung cancer. Mar 23, 2020 mok et al conducted a large phase iii study that compared gefitinib with carboplatin paclitaxel in the firstline setting in asian patients who had adenocarcinoma and had never smoked or were. Iressa gefitinib tablets contain 250 mg of gefitinib and are available as brown filmcoated tablets for daily oral administration. In arms a and b, the carboplatin and paclitaxel response rate, gefitinib response rate, and median survival durations were 34. Randomized phase iii study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma. The pemetrexedcisplatin regimen prolonged os as compared with gemcitabinecisplatin in patients with adenocarcinoma and large cell carcinoma. Final overall survival results from a randomised, phase. Based on the superior diseasefree survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these. Intercalating and maintenance gefitinib plus chemotherapy. Interstitial lung disease was observed in 1 patient from each arm. Sep 21, 2016 at the final analysis, neither dose of gefitinib improved overall survival when added to paclitaxel and carboplatin compared with paclitaxel and carboplatin plus placebo golrank p.
The primary objective was met, with a disease control in. Giving paclitaxel and carboplatin together with gefitinib may kill more tumor cells. What is the role of gefitinib in the treatment of non. The primary objective of the study was treatment efficacy, evaluated based on an endpoint of disease control at 16 weeks. Gefitinib should be withheld for up to 14 days for acute onset or worsening of pulmonary symptoms dyspnea, cough, fever, grade. Rectal metastasis from pulmonary adenocarcinoma is rare, and it has been regarded as an endstage phenomenon. Increase gefitinib dosage to 500 mg daily in the absence of severe adverse effects 1. Selected locally advanced patients may derive benefit from surgical resection after gefitinib therapy. Gefitinib versus cisplatin plus docetaxel in patients with. Phase ii study of gefitinib as a firstline therapy in. Nine out of 61 patients 15% developed grade 35 pneumonitis in the calgb trial 15. Highlights of prescribing information gastrointestinal. Lung adenocarcinoma accounts for 40% of all lung cancers. Gefitinib plus chemotherapy versus placebo plus chemotherapy.
Gefitinib or carboplatinpaclitaxel in pulmonary adenocarcinoma. Paclitaxel, carboplatin, and gefitinib in treating. Pdf gefitinib or carboplatinpaclitaxel in pulmonary. Younger people aged 2046 who have lung cancer are more likely to have lung adenocarcinoma than other lung cancers. Choi yj, lee dh, choi cm, lee js, lee sj, ahn jh, kim sw. Paclitaxelcarboplatin pc followed by gefitinib versus pc. This trial compared gefitinib, an inhibitor of the tyrosine kinase of epidermal growth factor egfr, with carboplatin plus paclitaxel as initial treatment of pulmonary adenocarcinoma in more than.
The 12month progression free rate of gefitinib compared with chemotherapy was found to. Metachronous rectal metastasis from pulmonary adenocarcinoma. Gefitinib is an egfr inhibitor, like erlotinib, which interrupts signaling through the epidermal growth factor receptor egfr in target cells. Lung adenocarcinoma starts in glandular cells, which secrete substances such as mucus, and tends to. The ifct0504 phase ii trial evaluated the efficacy of erlotinib versus carboplatinpaclitaxel cp as firstline treatment in cases of advanced lepidicpredominant adenocarcinoma adc. Relevant trials were identified from the databases of pubmed, embase, cochrane library, and the clinicaltrials. Randomized phase ii study of sequential carboplatin plus. Erlotinib versus carboplatin and paclitaxel in advanced. In july 2015, gefitinib was approved by the fda as firstline treatment of patients with metastatic nsclc whose tumors have egfr. In the ipass trial 1217 patients with advanced lung adenocarcinoma, of asian descent and light or never smokers were randomized to receive gefitinib versus carboplatin and paclitaxel. Pulmonary toxicities of gefitinib in patients with. The gefitinib trials are completed and none reported a corresponding significant difference in os 10 x 10.