Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Irinotecan

Cisplatin

Erlotinib Hydrochloride

Topoisomerase I Inhibitors

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Induction (with Erlotinib X 3 cycles) -\> CCRT with Erlotinib (X 2 cycles) -\> continue Erlotinib (X 6 cycles)

Induction (IP X 3 cycles) -\> CCRT with IP (X 2 cycles)

CCRT with IP (X 2 cycles) -\> consolidation IP (X 3 cycles)

Induction (Erlotinib X 3 cycles) -\> CCRT with IP (X 2 cycles) -\> recurrence -\> Erlotinib (until PD)

Erlotinib 150 mg p.o. daily x21 days every 3 weeks

Erlotinib

Irinotecan 65mg/m2 + Cisplatin 30mg/m2 IV on D1,D8 every 3 weeks X 3 cycles

Induction or consolidation IP chemotherapy

Irinotecan (60mg/m2) + cisplatin (30mg/m2) IV on D1 \& 8 every 3 weeks X 2 cycles

CCRT with IP chemotherapy (Irinotecan + Cisplatin)

CCRT :Concurrent Thoracic Radiotherapy (2.4 Gy/fr, Total 60 Gy, 25fr over 5 weeks)

CCRT

Sung JIn Yoon, Rn

Jin Soo Lee, M.D.

Heung Tae Kim, M.D.

Ji-Youn Han, M.D.

Geon Kook Lee, M.D.

Tak Yun, M.D.

Kwan Ho Cho, M.D.

Hong Ryull Pyo, M.D.

Bin Hwangbo, M.D.

Hee Seok Lee, M.D.

Kun young Lim, M.D.

Kyong-Ah Yoon, PH.D.

Byung-Ho Nam, Ph.D.

Young Ho Yun, M.D.

Jae-ill Zo, M.D.

The use of induction chemotherapy is feasible and effective. It is also logistically beneficial for decreasing micrometastases and radiation-related toxicity by decreasing tumor burden before definite locoregional concurrent therapy. Previously the investigators conducted several phase II study of IP chemotherapy in advanced NSCLC and demonstrated that IP chemotherapy has a promising activity and readily manageable toxicity profile. Given the encouraging activity of IP chemotherapy in the advanced stage setting, the investigators postulated that their further investigation in the stage III setting might lead to further prolongation of survival times. In addition to cisplatin, Irinotecan has been demonstrated to act as radiation sensitizers in preclinical and clinical setting. Therefore, their use with concurrent radiotherapy might lead to radiation sensitization and improved locoregional control.

Concurrent Chemoradiation therapy is widely accepted as a standard treatment of locally advanced unresectable stage III NSCLC. When compared with the result of radiation therapy alone of CALGB 8433 trial (i.e., 9.7 months), the median survival times have almost doubled over the last 2 decades, but rarely exceeded 18 months after chemoradiation therapy in most randomized trials. On the other hand, a significant portion of patients had to endure the side effects of grade 3/4 esophagitis and also pneumonitis, which resulted in treatment-related deaths in some cases. There is a great need to develop more effective but less toxic treatment strategies. Recently, molecular-targeted therapy using EGFR-TKIs brought new enthusiasm to the NSCLC therapy. The investigators observed a median survival time of 20.1 months in chemo-naïve never-smoker Korean patients with adenocarcinoma of the lung. The benefit of EGFR-TKI was also demonstrated in never-smokers who participated in the phase III trial of carboplatin/paclitaxel with or without Erlotinib (TRIBUTE). Despite a lack of benefit in the overall patient population, Erlotinib conferred a survival benefit to those who had never smoked cigarettes, In this analysis, 105 patients who were identified as never smokers had a median survival of 10 months, similar to the entire study population, when treated with carboplatin/paclitaxel plus placebo. However, for the patients in this subpopulation who were treated with Erlotinib and the same chemotherapy regimen, the median survival increased to 22.5 months (P = 0.01). Furthermore, EGFR mutation was associated with significantly higher response rate and longer survival as compared with those without EGFR mutation. More importantly, the median survival time of those patients with EGFR mutation-positive tumors exceeded 20 months in the majority of the studies. These results are very provocative given the fact that only the patients with stage IIIb not amenable to chemoradiation therapy and stage IV NSCLC patients were included in the study and in many studies, the majority of the patients were heavily pre-treated with multiple chemotherapy regimens. The investigators postulate that if the case were properly selected, EGFR-TKI would significantly improve the overall survival of the patients with locally advanced unresectable stage III NSCLC. The investigators therefore propose a randomized phase II trial to evaluate the efficacy and toxicity of EGFR-TKI Erlotinib in selected group of NSCLC patients with EGFR mutation-positive stage III tumors. The use of induction chemotherapy is feasible and effective. It is also logistically beneficial for decreasing micrometastases and radiation-related toxicity by decreasing tumor burden before definite locoregional concurrent therapy. Previously the investigators conducted several phase II study of IP chemotherapy in advanced NSCLC and demonstrated that IP chemotherapy has a promising activity and readily manageable toxicity profile. Given the encouraging activity of IP chemotherapy in the advanced stage setting, the investigators postulated that their further investigation in the stage III setting might lead to further prolongation of survival times. In addition to cisplatin, Irinotecan has been demonstrated to act as radiation sensitizers in preclinical and clinical setting. Therefore, their use with concurrent radiotherapy might lead to radiation sensitization and improved locoregional control.

Induction Chemotherapy Followed by CCRT According to EGFR Mutation Status in NSCLC III

A Randomized Phase II Study of Induction Chemotherapy Followed by Concurrent Chemoradiation Therapy According to EGFR Mutation Status in Patients With Unresectable Stage III NSCLC

Roche Pharma AG

Pfizer

National Cancer Center, Korea

President

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Induction Chemotherapy Followed by CCRT According to EGFR Mutation Status in NSCLC III	NCT00620269	Lung Cancer NSCLC	Erlotinib Induction or co... CCRT with IP ch... CCRT	18 Years -	National Cancer Center, Korea
Induction Chemotherapy Followed by CCRT According to EGFR Mutation Status in NSCLC III	NCT00620269	Lung Cancer NSCLC	Erlotinib Induction or co... CCRT with IP ch... CCRT	18 Years -	National Cancer Center, Korea

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