Randomized phase II study of paclitaxel/carboplatin intercalated with gefitinib compared to paclitaxel/carboplatin alone for chemotherapy-naïve non-small cell lung cancer in a clinically selected population excluding patients with non-smoking adenocarcinoma or mutated EGFR.
BACKGROUND
Considering cell cycle dependent cytotoxicity, intercalation of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) may be a treatment option in non-small cell lung cancer (NSCLC). This randomized phase 2 study compared the efficacy of paclitaxel and carboplatin (PC) intercalated with gefitinib (G) versus PC alone in a selected, chemotherapy-naïve population of advanced NSCLC patients with a history of smoking or wild-type EGFR.


METHODS
Eligible patients were chemotherapy-naïve advanced NSCLC patients with Eastern Cooperative Oncology Group performance status of 0-2. Non-smoking patients with adenocarcinoma or patients with activating EGFR mutation were excluded because they could benefit from gefitinib alone. Eligible patients were randomized to one of the following treatment arms: PCG, P 175 mg/m(2), and C AUC 5 administered intravenously on day 1 intercalated with G 250 mg orally on days 2 through 15 every 3 weeks for four cycles followed by G 250 mg orally until progressive disease; or PC, same dosing schedule for four cycles only. The primary endpoint was the objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity profile.


RESULTS
A total of 90 patients participated in the study. The ORRs were 41.9 % (95 % confidence interval (CI) 27.0-57.9 %) for the PCG arm and 39.5 % (95 % CI 25.0-55.6 %) for the PC arm (P = 0.826). No differences in PFS (4.1 vs. 4.1 months, P = 0.781) or OS (9.3 vs. 10.5 months, P = 0.827) were observed between the PCG and PC arms. Safety analyses showed a similar incidence of drug-related grade 3/4 toxicity. Rash and pruritus were more frequent in the PCG than in the PC arm.


CONCLUSIONS
PCG did not improve ORR, PFS, and OS compared to PC chemotherapy alone for NSCLC in a clinically selected population excluding non-smoking adenocarcinoma or mutated EGFR.


BACKGROUND
The study is registered with ClinicalTrials.gov ( NCT01196234 ). Registration date is 08/09/2010.
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro-43-gil, Songpa-gu, Seoul, 138-736, Korea. yoonji23@hanmail.net.|Division of Hemato-oncology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea. yoonji23@hanmail.net.
Yoon Ji
YJ
Choi
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro-43-gil, Songpa-gu, Seoul, 138-736, Korea. leedaeho@amc.seoul.kr.|Asan Institute for Life Science, Asan Medical Center, Institute for Innovative Cancer Research, Seoul, Korea. leedaeho@amc.seoul.kr.|University of Ulsan College of Medicine, Ulsan, Korea. leedaeho@amc.seoul.kr.
Dae Ho
DH
Lee
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro-43-gil, Songpa-gu, Seoul, 138-736, Korea. ccm@amc.seoul.kr.|Asan Institute for Life Science, Asan Medical Center, Institute for Innovative Cancer Research, Seoul, Korea. ccm@amc.seoul.kr.|University of Ulsan College of Medicine, Ulsan, Korea. ccm@amc.seoul.kr.
Chang Min
CM
Choi
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro-43-gil, Songpa-gu, Seoul, 138-736, Korea. jayslee@amc.seoul.kr.|Asan Institute for Life Science, Asan Medical Center, Institute for Innovative Cancer Research, Seoul, Korea. jayslee@amc.seoul.kr.|University of Ulsan College of Medicine, Ulsan, Korea. jayslee@amc.seoul.kr.
Jung Shin
JS
Lee
Asan Institute for Life Science, Asan Medical Center, Institute for Innovative Cancer Research, Seoul, Korea. sj_lee@amc.seoul.kr.
Seung Jin
SJ
Lee
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro-43-gil, Songpa-gu, Seoul, 138-736, Korea. drjiny@amc.seoul.kr.|Asan Institute for Life Science, Asan Medical Center, Institute for Innovative Cancer Research, Seoul, Korea. drjiny@amc.seoul.kr.|University of Ulsan College of Medicine, Ulsan, Korea. drjiny@amc.seoul.kr.
Jin-Hee
JH
Ahn
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro-43-gil, Songpa-gu, Seoul, 138-736, Korea. swkim@amc.seoul.kr.|Asan Institute for Life Science, Asan Medical Center, Institute for Innovative Cancer Research, Seoul, Korea. swkim@amc.seoul.kr.|University of Ulsan College of Medicine, Ulsan, Korea. swkim@amc.seoul.kr.
Sang-We
SW
Kim
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017239:Paclitaxel / Q000008:administration & dosage*; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011799:Quinazolines; D016190:Carboplatin; C512478:EGFR protein, human; D066246:ErbB Receptors; D017239:Paclitaxel; D000077156:Gefitinib