Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Amino Acids

Vitamins

Docetaxel

Pemetrexed

Mitogens

Tyrosine Kinase Inhibitors

Gefitinib

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Protein Kinase Inhibitors

Tyrosine

Folinic Acid

Folate

Vitamin B9

combined group chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycle is 6 depending on disease evaluation and patient's physical condition combined with gefitinib 250mg once per day from the start day of chemotherapy until disease progression or intolerable side effects.

sequenced group chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycles is 6 depending on disease evaluation or patient's physical condition sequenced by gefitinib 250mg once per day until disease progression or intolerable side effects.

chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycle is 6 depending on disease evaluation and patient's physical condition combined with gefitinib 250mg once per day from the start day of chemotherapy until disease progression or intolerable side effects.

combined group

Sequenced group

Mengzhao Wang, MD

Jing Zhao, MD

Wei Zhong, MD

There are two different treatment modes for NSCLC patients who failed to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) after initially responding to EGFR-TKI. One is EGFR-TKI combined with chemotherapy and the other is chemotherapy followed by EGFR-TKI. It is unclear which one is more suitable to this group of lung cancer patients. So this phase Ⅱclinical trial is designed to compare the efficiency and safety of these two different treatment modes.

Responses to EGFR-TKIs are quiet dramatic and durable, especially in patients with EGFR gene classic mutations, such as 19 deletion or 21 leucine 858 arginine(L858R). However, most patients with NSCLC who respond to EGFR-TKIs eventually experience progression of disease after approximately 12 months. The lack of an established therapeutic option for NSCLC patients who have progressive disease after EGFR-TKIs failure poses a great challenge to physicians in terms of how best to manage this growing group of lung cancer patients.

In clinical practice some of the initially EGFR-TKI sensitive tumors which progressed evidence a striking increase in tumor volume within several weeks, after being taken off EGFR-TKI. This response is called "rebound phenomenon". Most experts still believe that these tumors continue to be "oncogene-addicted" to EGFR. So it is rational that EGFR-TKI combined with another chemotherapy regimen can be used to treat NSCLC after the failure of EGFR-TKI therapy.

However in some phase Ⅱclinical trials involved a few NSCLC patients who failed to EGFR-TKI therapy, another treatment mode, that is to say, at least one cytotoxic chemotherapy was used firstly then switched to EGFR-TKI therapy until progression of disease, was used and called reintroduction or retreatment of EGFR-TKI. Using this treatment mode, some investigators reported the partial remission (PR) and disease control rate (DCR) were observed in 21.7%-36% and 65.2%-86% NSCLC patients.

Study of Chemotherapy Sequenced by or Combined With EGFR-TKIs for NSCLC Patients Failed to EGFR-TKIs Therapy

A Phase Ⅱ Randomized Controlled Trial to Compare Chemotherapy Sequenced by EGFR-TKIs and Chemotherapy Combined With EGFR-TKIs for Advanced or Metastatic NSCLC Patients Failed to EGFR-TKIs Therapy

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks.

From date of randomization until the date of death from any cause, assessed up to 100 weeks.

The objective response rate includes the complete remission and partial remission rate.

FACL-L is assessed at different time points.(Date of randomization,1 week after chemotherapy,every cycle of chemotherapy,every month of EGFR-TKI maintain treatment,up to 100 weeks)

The adverse events are assessed by National Cancer Institute-Common Toxicity Criteria(version3.0) (NCI-CTC).

Peking Union Medical College Hospital

Spots Global Cancer Trial Database for combined group