Survival After Hyperthermic Intraperitoneal Chemotherapy and Primary or Interval Cytoreductive Surgery in Ovarian Cancer: A Randomized Clinical Trial.

Importance: Ovarian cancer has the highest mortality rate among gynecologic malignant tumors. Data are lacking on the survival benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with ovarian cancer who underwent primary or interval cytoreductive surgery. Objective: To assess the clinical benefit of HIPEC after primary or interval maximal cytoreductive surgery in women with stage III or IV primary advanced ovarian cancer. Design, Setting, and Participants: In this single-blind randomized clinical trial performed at 2 institutions in South Korea from March 2, 2010, to January 22, 2016, a total of 184 patients with stage III or IV ovarian cancer with residual tumor size less than 1 cm were randomized (1:1) to a HIPEC (41.5 °C, 75 mg/m2 of cisplatin, 90 minutes) or control group. The primary end point was progression-free survival. Overall survival and adverse events were key secondary end points. The date of the last follow-up was January 10, 2020, and the data were locked on February 17, 2020. Exposures: Hyperthermic intraperitoneal chemotherapy after cytoreductive surgery. Main Outcomes and Measures: Progression-free and overall survival. Results: Of the 184 Korean women who underwent randomization, 92 were randomized to the HIPEC group (median age, 52.0 years; IQR, 46.0-59.5 years) and 92 to the control group (median age, 53.5 years; IQR, 47.5-61.0 years). After a median follow-up of 69.4 months (IQR, 54.4-86.3 months), median progression-free survival was 18.8 months (IQR, 13.0-43.2 months) in the control group and 19.8 months (IQR, 13.7-55.4 months) in the HIPEC group (P = .43), and median overall survival was 61.3 months (IQR, 34.3 months to not reported) in the control group and 69.5 months (IQR, 45.6 months to not reported) in the HIPEC group (P = .52). In the subgroup of interval cytoreductive surgery after neoadjuvant chemotherapy, the median progression-free survival was 15.4 months (IQR, 10.6-21.1 months) in the control group and 17.4 months (IQR, 13.8-31.5 months) in the HIPEC group (hazard ratio for disease progression or death, 0.60; 95% CI, 0.37-0.99; P = .04), and the median overall survival was 48.2 months (IQR, 33.8-61.3 months) in the control group and 61.8 months (IQR, 46.7 months to not reported) in the HIPEC group (hazard ratio, 0.53; 95% CI, 0.29-0.96; P = .04). In the subgroup of primary cytoreductive surgery, median progression-free survival was 29.7 (IQR, 17.2-90.1 months) in the control group and 23.9 months (IQR, 12.3-71.5 months) in the HIPEC group, and the median overall survival was not reached in the control group and 71.3 months (IQR, 45.6 months to not reported) in the HIPEC group. Conclusions and Relevance: The addition of HIPEC to cytoreductive surgery did not improve progression-free and overall survival in patients with advanced epithelial ovarian cancer. Although the results are from a subgroup analysis, the addition of HIPEC to interval cytoreductive surgery provided an improvement of progression-free and overall survival. Trial Registration: ClinicalTrials.gov Identifier: NCT01091636.

Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer After Preoperative Chemoradiotherapy (ADORE): Long-Term Results of a Randomized Controlled Trial.

PURPOSE: We evaluated the role of oxaliplatin as adjuvant chemotherapy in patients with rectal cancer who received preoperative chemoradiotherapy (CRT) with fluoropyrimidine monotherapy and total mesorectal excision (TME). METHODS: The ADORE trial (adjuvant oxaliplatin in rectal cancer) is a multicenter, randomized trial in patients with postoperative ypStage II (ypT3-4N0) or III (ypTanyN1-2) rectal cancer after fluoropyrimidine-based preoperative CRT and TME. Patients were randomly assigned (1:1) to receive adjuvant chemotherapy either with FL (fluorouracil 380 mg/m2 and leucovorin 20 mg/m2) or FOLFOX (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and fluorouracil bolus 400 mg/m2 on day 1, fluorouracil infusion 2,400 mg/m2 for 46 hours). Stratification factors included ypStage and participating center. Primary end point was disease-free survival (DFS). RESULTS: A total of 321 patients were enrolled between November 19, 2008, and June 12, 2012. Six-year DFS rates were 68.2% in the FOLFOX arm versus 56.8% in the FL arm, with a stratified hazard ratio of 0.63 (95% CI, 0.43 to 0.93; P = .018) by intention-to-treat analysis. In the subgroup analysis for DFS, FOLFOX was favorable versus FL in patients with ypStage III, ypN1b, ypN2, high-grade histology, minimally regressed tumor, and an absence of lymphovascular or perineural invasion. Six-year overall survival rate was 78.1% in the FOLFOX arm versus76.4% in the FL arm (hazard ratio, 0.73; 95% CI, 0.45 to 1.19; P = .21). In the subgroup analysis for OS, FOLFOX was favorable versus FL in patients with ypN2 and minimally regressed tumor. CONCLUSION: Adjuvant FOLFOX improved DFS in patients with rectal cancer with ypStage II and III disease after preoperative CRT. Adjuvant FOLFOX may be considered on the basis of the postoperative pathologic stage in those who received preoperative CRT and TME.

Primary Tumor Characteristics Are Important Prognostic Factors for Sorafenib-Treated Patients with Metastatic Renal Cell Carcinoma: A Retrospective Multicenter Study.

We aimed to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with sorafenib. We investigated 177 patients, including 116 who received sorafenib as first-line therapy, using the Cox regression model. During a median follow-up period of 19.2 months, the PFS and OS were 6.4 and 32.6 months among all patients and 7.4 months and undetermined for first-line sorafenib-treated patients, respectively. Clinical T3-4 stage (hazard ratio [HR] 2.56) and a primary tumor size >7 cm (HR 0.34) were significant prognostic factors for PFS among all patients, as were tumor size >7 cm (HR 0.12), collecting system invasion (HR 5.67), and tumor necrosis (HR 4.11) for OS (p < 0.05). In first-line sorafenib-treated patients, ≥4 metastatic lesions (HR 28.57), clinical T3-4 stage (HR 4.34), collecting system invasion (univariate analysis HR 2.11; multivariate analysis HR 0.07), lymphovascular invasion (HR 13.35), and tumor necrosis (HR 6.69) were significant prognosticators of PFS, as were bone metastasis (HR 5.49) and clinical T3-4 stages (HR 4.1) for OS (p < 0.05). Our study thus identified a number of primary tumor-related characteristics as important prognostic factors in sorafenib-treated mRCC patients.

The Korean Gastric Cancer Cohort Study: Study Protocol and Brief Results of a Large-Scale Prospective Cohort Study.

PURPOSE: This study aimed to establish a large-scale database of patients with gastric cancer to facilitate the development of a national-cancer management system and a comprehensive cancer control policy. MATERIALS AND METHODS: An observational prospective cohort study on gastric cancer was initiated in 2010. A total of 14 cancer centers throughout the country and 152 researchers were involved in this study. Patient enrollment began in January 2011, and data regarding clinicopathological characteristics, life style-related factors, quality of life, as well as diet diaries were collected. RESULTS: In total, 4,963 patients were enrolled until December 2014, and approximately 5% of all Korean patients with gastric cancer annually were included. The mean age was 58.2±11.5 years, and 68.2% were men. The number of patients in each stage was as follows: 3,394 patients (68.4%) were in stage IA/B; 514 patients (10.4%), in stage IIA/B; 469 patients (9.5%), in stage IIIA/B/C; and 127 patients (2.6%), in stage IV. Surgical treatment was performed in 3,958 patients (79.8%), endoscopic resection was performed in 700 patients (14.1%), and 167 patients (3.4%) received palliative chemotherapy. The response rate for the questionnaire on the quality of life was 95%; however, diet diaries were only collected for 27% of patients. CONCLUSIONS: To provide comprehensive information on gastric cancer for patients, physicians, and government officials, a large-scale database of Korean patients with gastric cancer was established. Based on the findings of this cohort study, an effective cancer management system and national cancer control policy could be developed.

Efficacy and Safety of Sorafenib Therapy on Metastatic Renal Cell Carcinoma in Korean Patients: Results from a Retrospective Multicenter Study.

OBJECTIVE: To evaluate the efficacy and safety of sorafenib for Korean patients with metastatic renal cell carcinoma (mRCC). METHODS: A total of 177 mRCC patients using sorafenib as first- (N = 116), second- (N = 43), and third-line (N = 18) therapies were enrolled from 11 Korean centers between 2006 and 2012. The patient characteristics, therapy duration, tumor response, disease control rate, and tolerability were assessed at baseline and at routine follow-ups, and the progression-free survival (PFS) and overall survival (OS) times and rates were analyzed. RESULTS: Among all patients, 18 (10.2%) stopped sorafenib treatment for a median of 1.7 weeks, including 15 (8.5%) who discontinued the drug, while 40 (22.6%) and 12 (6.8%) patients required dose reductions and drug interruptions, respectively. Severe adverse events (AEs) or poor compliance was observed in 64 (36.2%) patients, with 118 (7.4%) ≥grade 3 AEs. During the treatment, one myocardial infarction was observed. The number of ≥grade 3 AEs in the first-line sorafenib group was 71 (6.8% of the total 1048 AEs). During a median follow-up of 17.2 months, the radiologically confirmed best objective response rate, disease control rate, median PFS, and median OS were 22.0%, 53.0%, 6.4 months (95% confidence interval [CI], 5.2-8.9), and 32.6 months (95% CI, 27.3-63.8) for the total 177 sorafenib-treated patients, respectively, and 23.2%, 56.0%, 7.4 months (95% CI, 5.5-10.5), and not reached yet (95% CI, 1.0-31.1) for the first-line sorafenib group, respectively. CONCLUSIONS: Sorafenib produced tolerable safety, with a ≥grade 3 AE rate of 7.4% and an acceptable disease control rate (53.0%) in Korean mRCC patients.

Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial.

BACKGROUND: The role of adjuvant chemotherapy for patients with rectal cancer is controversial, especially when used after preoperative chemoradiotherapy. Fluoropyrimidine-based adjuvant chemotherapy, including fluorouracil and leucovorin, has been widely used; however, the addition of oxaliplatin to fluorouracil and leucovorin (FOLFOX), a standard adjuvant regimen for colon cancer, has not been tested in rectal cancer. We aimed to compare the efficacy and safety of adjuvant fluorouracil and leucovorin with that of FOLFOX in patients with locally advanced rectal cancer after preoperative chemoradiotherapy. METHODS: In this open-label, multicentre, phase 2, randomised trial, patients with postoperative pathological stage II (ypT3-4N0) or III (ypTanyN1-2) rectal cancer after preoperative fluoropyrimidine-based chemoradiotherapy and total mesorectal excision were recruited and randomly assigned (1:1) via a web-based software platform to receive adjuvant chemotherapy with either four cycles of fluorouracil and leucovorin (fluorouracil 380 mg/m(2) and leucovorin 20 mg/m(2) on days 1-5, every 4 weeks) or eight cycles of FOLFOX (oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), and fluorouracil bolus 400 mg/m(2) on day 1, and fluorouracil infusion 2400 mg/m(2) for 46 h, every 2 weeks). Stratification factors were pathological stage (II vs III) and centre. Neither patients nor investigators were masked to group assignment. The primary endpoint was 3-year disease-free survival, analysed by intention to treat. This study is fully enrolled, is in long-term follow-up, and is registered with ClinicalTrials.gov, number NCT00807911. FINDINGS: Between Nov 19, 2008, and June 12, 2012, 321 patients were randomly assigned to fluorouracil and leucovorin (n=161) and FOLFOX (n=160). 141 (95%) of 149 patients in the fluorouracil plus leucovorin group and 141 (97%) of 146 in the FOLFOX group completed all planned cycles of adjuvant treatment. Median follow-up was 38·2 months (IQR 26·4-50·6). 3-year disease-free survival was 71·6% (95% CI 64·6-78·6) in the FOLFOX group and 62·9% (55·4-70·4) in the fluorouracil plus leucovorin group (hazard ratio 0·657, 95% CI 0·434-0·994; p=0·047). Any grade neutropenia, thrombocytopenia, fatigue, nausea, and sensory neuropathy were significantly more common in the FOLFOX group than in the fluorouracil plus leucovorin group; however, we noted no significant difference in the frequency of these events at grade 3 or 4. The most common grade 3 or worse adverse events were neutropenia (38 [26%] of 149 patients in the fluorouracil plus leucovorin group vs 52 [36%] of 146 patients in the FOLFOX group), leucopenia (eight [5%] vs 12 [8%]), febrile neutropenia (four [3%] vs one [<1%]), diarrhoea (four [3%] vs two [1%]), and nausea (one [<1%] vs two [1%]). INTERPRETATION: Adjuvant FOLFOX improves disease-free survival compared with fluorouracil plus leucovorin in patients with locally advanced rectal cancer after preoperative chemoradiotherapy and total mesorectal excision, and warrants further investigation. FUNDING: Korea Healthcare Technology R&D Project (South Korean Ministry of Health and Welfare).

Intravenous iron supplementation may be superior to observation in acute isovolemic anemia after gastrectomy for cancer.

AIM: To determine whether the application of post-operative intravenous (IV)-iron for acute isovolemic anemia after gastrectomy for cancer may be effective. METHODS: Among 2078 gastric cancer patients who underwent surgery between February 2007 and August 2009 at the National Cancer Center Korea, 368 patients developed post-operative anemia [hemoglobin-(Hb)-level < 9 g/dL] within the first postoperative week. Patients requiring transfusions were excluded. IV-iron was administered to 63 patients (iron group). Sixty patients were observed without treatment (observation group). The clinical outcomes of the groups were compared concerning clinicopathologic data, morbidity, and changes in Hb levels using Fisher's exact test, Student's t-test and the Z-test. RESULTS: The initial Hb level was higher in the iron group than in the observation group (7.3 ± 1.0 g/dL vs 8.4 ± 0.5 g/dL, P < 0.001). The slope of the changes in the Hb level was significantly higher in the iron group than in the observation group (0.648 ± 0.054 vs 0.349 ± 0.038, P < 0.001). The Hb level 1 and 3 mo post-operatively increased from 10.7 ± 1.3 to 11.9 ± 1.3 g/dL in the iron group (P = 0.033) and from 10.1 ± 1.0 to 10.8 ± 1.4 g/dL in the observation group (P < 0.001). The postoperative hospital stay was significantly longer in the iron group than in the observation group (10.5 ± 6.8 d vs 7.6 ± 5.5 d, P = 0.011). There were no significant differences in the major and surgical complications between the groups (6.3% vs 13.3%, P = 0.192; 9.5% vs 3.3%, P = 0.164). CONCLUSION: IV-iron supplementation may be an effective treatment for post-operative isovolemic post-gastrectomy anemia and may be a better alternative than observation.

Phase II study of concurrent transarterial chemoembolization and sorafenib in patients with unresectable hepatocellular carcinoma.

BACKGROUND & AIMS: Transarterial chemoembolization (TACE) is an important palliative treatment for unresectable hepatocellular carcinoma (HCC), but TACE-induced ischemic injury can upregulate angiogenic factors and is associated with poor prognosis. The aim of this study was to evaluate the safety and efficacy of concurrent conventional TACE and sorafenib in patients with unresectable HCC. METHODS: The primary objectives of this prospective, single-arm, phase II study were to evaluate safety and time to progression (TTP). Sorafenib was given 3 days after TACE and was administered for up to 24 weeks. Repeated TACE was performed on demand. Tumor response was assessed every 8 weeks. RESULTS: Fifty patients were treated and followed from July 2009 to May 2011. All patients were in Barcelona Clinic Liver Cancer (BCLC) stage B (82%) or C (18%). The median time of follow-up was 14.9 months and a median of 1 TACE session was given (range, 1-4). The median dose intensity of sorafenib was 68.7% (range, 37.3-100) of 800 mg daily. The most common reasons for dose reduction were hand-foot syndrome and thrombocytopenia. Thirty patients completed the study and 17 patients discontinued sorafenib due to disease progression. The overall median TTP was 7.1 months (95% confidence interval (CI), 4.8-7.5 months): 7.3 months in BCLC stage B; 5.0 months in BCLC stage C. The 6-month progression-free survival rate was 52% (95% CI, 37.3-66.1). CONCLUSIONS: Concurrent treatment of unresectable HCC with conventional TACE and sorafenib demonstrates a manageable safety profile and a possibility of promising efficacy.

Predictive factors of pathologic complete response and clinical tumor progression after preoperative chemotherapy in patients with stage II and III breast cancer.

BACKGROUND: This study aimed to define predictive factors of pathologic complete response (pCR) and disease progression in stage II and III breast cancer patients. PATIENTS AND METHODS: Three hundred thirty-eight patients were included in the study. Patients had received preoperative chemotherapy as follows: 101 had doxorubicin plus cyclophosphamide (AC); 91 had doxorubicin plus docetaxel; 103 had docetaxel plus capecitabine; and 43 had paclitaxel plus gemcitabine. A pCR was defined as the absence of residual invasive carcinoma in the breast. RESULTS: The majority of patients (73%) were premenopausal with a median age of 44 (range, 21-76) years. Fifty-four patients (16%) achieved pCR and were distributed among the 4 breast cancer subtypes as follows: 10% of patients with -ER or PR+/HER2-, 13% with ER or PR+/HER2+, 33% with ER-/PR-/HER2+, and 19% with ER-/PR-/HER2-(p = 0.001). Taxane-containing regimen (p = 0.042) and Breast cancer subtype (p = 0.005) were significant predictive variables for pCR. On the other hand, significantly more patients who received non-taxane-containing regimen (AC) experienced no response (p = 0.001) or progression (p = 0.006). CONCLUSIONS: Patients with ER-/PR-/HER2+ tumors and those who received taxane-containing regimen achieved a higher pCR rate, while significantly more patients developed tumor progression by preoperative non-taxane-containing regimen (AC) compared to those who received taxane-containing chemotherapy.

Survival of patients with advanced hepatocellular carcinoma: sorafenib versus other treatments.

BACKGROUND AND AIM: Although sorafenib is recommended for patients with advanced hepatocellular carcinoma (HCC), a substantial portion of HCC patients in Asia are still treated with other treatments, mainly due to the prohibitive cost of sorafenib. We aimed to evaluate the clinical outcome of patients treated with sorafenib and those treated with other modalities in a single-center cohort. METHODS: We reviewed the medical records of two groups of consecutive patients with advanced HCC, according to applied treatment modalities, between January 2007 and September 2009 as follows: patients who received sorafenib for 6 weeks or more (n=123) and patients who were treated with one or more of other treatments, including transarterial chemoembolization, radiation, and cytotoxic chemotherapy (n=253). RESULTS: Overall survival did not differ significantly between these two groups (8.4 vs 8.2 months; P=0.601). Significant prognostic factors were high α-fetoprotein (≥200 ng/mL), massive/infiltrative intrahepatic tumors, macrovascular invasion, extrahepatic spread, and higher tumor-node-metastasis stage. Subgroup analysis, according to these factors, showed that sorafenib resulted in superior survival in patients with extrahepatic spread (hazard ratio [HR]=0.539; P=0.003) and massive/infiltrative tumors (HR=0.680; P=0.036). In the absence of each prognostic factor, other treatments were better than sorafenib. CONCLUSIONS: Considering the survival benefit for sorafenib over other treatments in patients with extrahepatic spread and massive/infiltrative intrahepatic tumors, these characteristics might be regarded as compelling indications for sorafenib.

Analysis of chemotherapy-induced amenorrhea rates by three different anthracycline and taxane containing regimens for early breast cancer.

PURPOSE: Chemotherapy-induced amenorrhea (CIA) by newer taxane-containing regimens was evaluated in early breast cancer (EBC) patients. METHODS: A prospective cohort of 122 premenopausal EBC patients participated in a phase III trial of preoperative docetaxel/capecitabine (TX) versus doxorubicin/cyclophosphamide (AC); 34 patients received adjuvant AC followed by paclitaxel (T) and 129 patients received 5-fluorouracil/doxorubicin/cyclophosphamide (FAC). RESULTS: The CIA rate was 90.2% with TX/AC, 73.5% with AC followed by T, and 72.1% with FAC at 1 year (P = 0.002), and 66.7%, 73.3%, and 58.9%, respectively, at 3 years (P = 0.268). At one year, age (P < 0.001) and taxane use (P = 0.002), and after two years, age and tamoxifen use were significant factors for CIA in multivariate analysis. Serum estradiol and follicle-stimulating hormone levels were significantly correlated with menstrual status, age, and tamoxifen use. CONCLUSION: Taxanes resulted in higher CIA rates in the first year, but age and tamoxifen use were significant factors for persistent CIA.

A randomized phase-III trial of docetaxel/capecitabine versus doxorubicin/cyclophosphamide as primary chemotherapy for patients with stage II/III breast cancer.

We aimed to determine the efficacies of a non-anthracycline-containing regimen, docetaxel/capecitabine (TX), in comparison with an anthracycline-containing regimen, doxorubicin/cyclophosphamide (AC), as primary chemotherapy for node-positive early stage breast cancer. In this phase-III single center randomized study, we randomized 209 women with axillary node positive, stage II/III breast cancer to receive four cycles of either TX or AC followed by surgery and cross-over to the other treatment as an adjuvant therapy. The primary endpoint was tumor pathologic complete response (pCR). Clinical response rates, toxicity profiles, disease free survival (DFS), and overall survival were secondary objectives. In total, 204 patients had clinical and radiological evaluation of response, and underwent surgery. Compared with AC, TX increased pCR in primary tumors (21% vs. 10%, respectively, P = 0.024) and clinical response (84% vs. 65%, P = 0.003). TX was associated with less nausea and vomiting, but more stomatitis, diarrhea, myalgia, and skin/nail changes than AC. With a median follow-up of 37 months, there was no significant difference in DFS by treatment groups (P = 0.932). Fewer patients developed recurrence who achieved pCR in lymph node (LN) (P = 0.025; hazard ratio, 0.189; 95% CI, 0.044-0.815) in the multivariate analysis. TX showed superior efficacies to AC with increased pathologic and clinical complete response rates. Although these findings did not translate into a gain in DFS, the patients who achieved pCR in LN developed significantly less recurrence.

Stroke risk prediction model: a risk profile from the Korean study.

BACKGROUND AND PURPOSE: The objective of this study was to develop the stroke risk prediction model among Korean population with high risk of stroke. METHODS: The data in this prospective cohort study came from 47,233 stroke events occurring over 13 years among 1,223,740 Koreans, aged 30-84 years, who were insured by the National Health Insurance Corporation (NHIC) and take a biennial medical examination from 1992 to 1995. The Cox proportional Hazard Model was used to develop the Korean Stroke Risk Prediction (KSRP) model for each sex. Also, the split-half method was applied for developing a model with the first half and for testing with the rest. RESULTS: The average 10-year risk for stroke was 3.52% for men and 3.66% for women. In general, actual stroke event rates were similar to the event rates predicted by the KSRP model. The discrimination using the KSRP model in the Korean cohort was high: the area under the receiver operating characteristic curve was 0.8165 [95% confidence interval (CI), 0.7993-0.8337] for men and 0.8095 (0.7875-0.8315) for women. A graded association between predicted stroke risk and actual stroke event was observed in men [highest versus lowest deciles of the predicted risk (hazard ratio (HR) 63.17; 95% confidence interval (CI), 52.30-76.31)] and in women (HR, 120.34; 95% CI, 85.31-169.77). CONCLUSIONS: The KSRP model could be used to predict the risk of stroke and would provide a useful guide to identify the groups at high risk for stroke among Korean.

The role of gefitinib treatment for Korean never-smokers with advanced or metastatic adenocarcinoma of the lung: a prospective study.

PURPOSE: This prospective trial was conducted to evaluate the role of gefitinib in never-smokers with advanced or metastatic adenocarcinoma of the lung. PATIENTS AND METHODS: The main inclusion criteria were stage IIIB/IV adenocarcinoma of the lung and status as a lifetime never-smoker. Patients received a 250-mg single oral daily dose of gefitinib until disease progression, unacceptable toxicity, or patient's refusal. Tumor response was assessed after every two 4-week cycles according to the World Health Organization response criteria. Additional analyses were performed to identify predictors of response and survival. RESULTS: Between August 2003 and March 2005, 72 Korean patients were enrolled; 55 chemotherapy naive, 17 previously treated; 6 male, 66 female; and ECOG PS 0/1/2, 24/42/4. All patients were assessed for response, toxicity, quality of life, and survival. Overall objective tumor response rate was 55.6% (95% confidence interval [CI], 43.4-67.3%). With a median follow-up of 23 months, the median survival time was 19.7 months (95% CI, 18.5-21.0 months) with a 1-year survival rate of 76.3%. The median duration of response was 6.8 months (95% CI, 4.7-9.0 months). Therapy-related improvement of symptoms and quality of life was observed within 2 to 4 weeks after the commencement of therapy in the responders. In a multivariate Cox proportional hazard model, good performance status and no prior history of chemotherapy were the two significant predictors of better survival (p = 0.005 and 0.042). CONCLUSION: Gefitinib showed very promising antitumor activity and survival outcome in Korean never-smokers with adenocarcinoma of the lung. It seems to be a good alternative to standard chemotherapy as a first-line therapy for this subgroup.