Female reproductive factors, gene polymorphisms in the estrogen metabolism pathway, and risk of lung cancer in Chinese women.

The authors examined relations between reproductive factors and 5 estrogen pathway gene polymorphisms (CYP17 rs743572, CYP19A1 rs10046, ERß rs1256049, ERß rs4986938, and COMT rs4680) among 702 Singapore Chinese female lung cancer cases and 1,578 hospital controls, of whom 433 cases (61.7%) and 1,375 controls (87.1%) were never smokers. Parity (per child, odds ratio (OR) = 0.92, 95% confidence interval (CI): 0.87, 0.97) and menstrual cycle length (for ≥30 days vs. <30 days, OR = 0.50, 95% CI: 0.32, 0.80) were inversely associated with lung cancer in never smokers, while age at first birth (for ages 21-25, 26-30, and ≥31 years vs. ≤20 years, ORs were 1.54, 2.17, and 1.30, respectively), age at menopause (for ages 49-51 and ≥52 years vs. ≤48 years, ORs were 1.37 and 1.59; P(trend) = 0.003), and reproductive period (for 31-33, 34-36, 37-39, and ≥40 years vs. ≤30 years, ORs were 1.06, 1.25, 1.45, and 1.47; P(trend) = 0.026) were positively associated. Among smokers, parity was inversely associated with lung cancer, but there was no association with other reproductive factors. The COMT rs4680 A allele was positively associated with lung cancer in never smokers (for G/A or A/A vs. G/G, OR = 1.46, 95% CI: 1.12, 1.90) but not in ever smokers. No associations were seen with other polymorphisms. These results support a risk-enhancing role of estrogens in lung carcinogenesis among never smokers.

Polymorphisms in inflammatory pathway genes, host factors and lung cancer risk in Chinese female never-smokers.

Inflammation appears to be important in lung carcinogenesis among smokers, but its role among never-smokers is not well established. We hypothesized that inflammatory medical conditions and gene polymorphisms interact to increase lung cancer risk in never-smokers. We interviewed 433 Singaporean female never-smoker lung cancer patients and 1375 hospital controls, and evaluated six polymorphisms in the interleukin 1-ß, interleukin 6 (IL6), cyclooxygenase-2, peroxisome proliferator-activated receptor-γ and interleukin 1-ß receptor antagonist (IL1RN) genes. Tuberculosis was associated with a non-significant elevated risk of lung cancer [odds ratio (OR) 1.58, 95% confidence interval (CI) 0.95-2.62]. There was no effect of asthma, atopy or chronic productive cough individually. However, the presence of one or more of these conditions (asthma, cough or atopy) increased risk (OR 2.24, 95%CI 1.15-4.38) in individuals possessing the T/T genotype at interleukin 1-ß -31T/C, but not in those possessing the C/T (OR 0.87, 95%CI 0.51-1.57) or C/C genotypes (OR 0.58, 95%CI 0.27-1.27), and in individuals having the *2 variable number of tandem repeat allele of IL1RN [OR 5.09 (1.39-18.67)], but not in those without (OR 0.93, 95%CI 0.63-1.35). The IL6-634 G allele increased the risk of lung cancer (OR 1.44, 95%CI 1.07-1.94). Lung cancer risk also increased with the number of polymorphism sites where at least 1 'risk' allele was present [interleukin 1-ß -31T/C (T allele), IL1RN (*2 allele) and IL6-634C/G (G allele)] among those with asthma, cough or atopy (Ptrend 0.001) but not in those without (Ptrend 0.47). Our results suggest that the effect of inflammatory medical conditions on lung cancer in never-smokers is modulated by host genetic susceptibility and will need to be confirmed in other studies conducted in similar populations.

Meat consumption and risk of lung cancer among never-smoking women.

The relationship between diet and lung cancer, apart from the protective effect of fruit and vegetables, is poorly understood. Reports on the role of dietary components such as meat are inconsistent, and few studies include sufficient numbers of nonsmokers. We examined the relationship between meat consumption and never-smoking lung cancer in a hospital-based case-control study of Singapore Chinese women, a population with low smoking prevalence. Three hundred and ninety-nine cases and 815 controls were recruited, of whom 258 cases and 712 controls were never smokers. A standardized questionnaire (which included a food frequency questionnaire module) was administered by trained interviewers. Among these never smokers, fruit and vegetable intake were inversely associated with lung cancer risk. Seventy-two percent of meat consumed was white meat (chicken or fish). Meat consumption overall was inversely associated with lung cancer [adjusted odds ratio (OR), 0.88, 0.59 for second, third tertiles, P (trend) = .012]. An inverse relationship between fish consumption and lung cancer (adjusted OR, 0.81, 0.47 for 2nd, 3rd tertiles, P (trend) < .001) was observed. No association was seen between consumption of processed meats and lung cancer, nor between dietary heterocyclic amines and lung cancer. Our data suggest that fish consumption may be protective against lung cancer in never smokers.

Assessment of human papillomavirus and Epstein-Barr virus in lung adenocarcinoma.

The association of human papillomavirus (HPV) and Epstein-Barr virus (EBV) infection with non-small cell lung cancer is controversial. HPV and EBV prevalence in a uniform population of lung adenocarcinoma was investigated, hypothesizing that there would be differences seen between smokers and non-smokers and between sexes. Patients involved in this study were selected from a single institution database of lung cancer. In total 497 patients with adenocarcinoma were identified and 110 patients had sufficient tissue for analysis with an in situ hybridization method that probed for high-risk and low-risk HPV and EBV. There were 65 males and 45 females, 78 patients with stage I-IIIA disease and 32 patients with stage IIIB-IV disease. There were similar number of smokers and non-smokers. Across all stages HPV and EBV staining was absent from all tissues examined. It is unlikely that HPV or EBV is an important etiological agent in adenocarcinoma of the lung, even among the never-smokers.

Induction concurrent chemoradiotherapy using Paclitaxel and Carboplatin combination followed by surgery in locoregionally advanced non-small cell lung cancer--Asian experience.

INTRODUCTION: It has been established that combined chemoradiotherapy treatment benefits selected patients with stage III Non Small Cell Lung Cancer (NSCLC). However, locoregional recurrence still poses a problem. The addition of surgery as the third modality may provide a possible solution. We report our experience of using the triple-modality approach in this group of patients. MATERIALS AND METHODS: This is a retrospective review of 33 patients with stage III NSCLC treated between 1997 and 2005. Patients have good performance status and no significant weight loss. There were 26 males (79 %) with median age of 63 years (range, 43 to 74) and median follow-up of 49 months. Seventy-six percent had Stage IIIA disease. Chemotherapy consisted of paclitaxel at 175 mg/m2 over 3 hours followed by carboplatin at AUC of 5 over 1 hour. Thoracic radiotherapy was given concurrently with the second and third cycles of chemotherapy. All patients received 50 Gray in 25 fractions over 5 weeks. RESULTS: The main toxicities were grade 3/4 neutropenia (30%), grade 3 infection (15 %) and grade 3 oesophagitis (9%). Twenty-five patients (76%) underwent surgery. Of the 8 who did not undergo surgery, 1 was deemed medically unfit after induction chemoradiotherapy and 4 had progressive disease; 3 declined surgery. Nineteen patients (58 %) had lobectomy and 6 had pneumonectomy. The median overall survival was 29.9 months and 12 patients are still in remission. CONCLUSION: The use of the triplemodality approach is feasible, with an acceptable tolerability and resectability rate in this group of patients.

Differences between small-cell lung cancer and non-small-cell lung cancer among tobacco smokers.

It is known that smoking increases the risk for all histological subtypes of lung cancer. To date, the factors that determine why some patients develop small-cell lung cancer (SCLC) while others develop non-small-cell lung cancer (NSCLC) remain unknown. We compared the characteristics of 774 smokers with SCLC and NSCLC diagnosed during the period January 1999 till December 2002. Multivariate logistic regression was used to estimate the odds ratio (OR) with 95% CI. Testing of linear trend across categories of pack-years was also conducted. Six hundred and sixty-five NSCLC were compared to 109 SCLC. Among SCLC, there were significantly more females (20.2% versus 12.8%), current-smokers (81.7% versus 71.9%) as well as smokers who had smoked more than 40 pack-years (75.6% versus 50.3%). Comparing SCLC with NSCLC among the men only, having smoked more than 40 pack-years was associated with a significantly elevated odds ratio (OR) of 3.71 of developing SCLC (95% CI, 1.05-13.1; p=0.041). There was a decreasing trend in OR with increasing smoking cessation period. When comparing SCLC with adenocarcinoma, the women had a higher OR of 2.37 of developing SCLC (95% CI, 1.05-5.31; p=0.037) compared to the men. Our findings suggest that cumulative smoking exposure in terms of pack-years smoked is an important determining factor for the preferred development of SCLC among smokers.

Survival of small-cell lung cancer and its determinants of outcome in Singapore.

INTRODUCTION: The survival and epidemiology of small-cell lung cancer (SCLC) in Singapore has not been described. We aim to present the characteristics as well as determine the survival outcome and important prognostic factors for SCLC patients. MATERIALS AND METHODS: A retrospective analysis of SCLC patients diagnosed from 1999 to 2002 was conducted at the Outram campus, Singapore. Clinical characteristics and treatment data were obtained from case records and survival data were checked with the registry of births and deaths on 30 May 2005. RESULTS: One hundred and eleven patients were analysed. There were 38 (34.2%) limited-disease (LD) patients and 73 (65.8%) extensive-disease (ED) patients. The majority were current or former smokers (94.7% among LD and 94.5% among ED). More patients with LD had good performance status (92% versus 63%, P = 0.0003) and were treated with combined chemotherapy and radiotherapy (82% versus 48%, P = 0.012). The median survival time of LD patients treated with curative chemoradiotherapy was 14.2 months (95% CI, 10.96 to 17.44). Those given prophylactic cranial irradiation had a median survival time of 16.9 months (95% CI, 11.83 to 21.97). For ED patients, the median survival time was 8.17 months (95%CI, 5.44 to 10.89). None of the factors analysed were significant prognostic factors for LD patients while performance status and type of treatment given were significant among ED patients. CONCLUSIONS: We found that the characteristics and survival of SCLC patients in Singapore are fairly similar to that of other countries.

Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety.

PURPOSE: The Intergroup 00-99 Trial for nasopharyngeal cancer (NPC) showed a benefit of adding chemotherapy to radiotherapy. However, there were controversies regarding the applicability of the results to patients in endemic regions. This study aims to confirm the findings of the 00-99 Trial and its applicability to patients with endemic NPC. PATIENTS AND METHODS: Between September 1997 and May 2003, 221 patients were randomly assigned to receive radiotherapy (RT) alone (n = 110) or chemoradiotherapy (CRT; n = 111). Patients in both arms received 70 Gy in 7 weeks using standard RT portals and techniques. Patients on CRT received concurrent cisplatin (25 mg/m2 on days 1 to 4) on weeks 1, 4, and 7 of RT and adjuvant cisplatin (20 mg/m2 on days 1 to 4) and fluorouracil (1,000 mg/m2 on days 1 to 4) every 4 weeks (weeks 11, 15, and 19) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. The median follow-up time was 3.2 years. RESULTS: Distant metastasis occurred in 38 patients on RT alone and 18 patients on CRT. The difference in 2-year cumulative incidence was 17% (95% CI, 14% to 20%; P = .0029). The hazard ratio (HR) for disease-free survival was 0.57 (95% CI, 0.38 to 0.87; P = .0093). The 2- and 3-year overall survival (OS) rates were 78% and 85% and 65% and 80% for RT alone and CRT, respectively. The HR for OS was 0.51 (95% CI, 0.31 to 0.81; P = .0061). CONCLUSION: This report confirms the findings of the Intergroup 00-99 Trial and demonstrates its applicability to endemic NPC. This study also confirms that chemotherapy improves the distant metastasis control rate in NPC.

Electroacupuncture for refractory acute emesis caused by chemotherapy.

PURPOSE: To evaluate the efficacy of electroacupuncture in preventing anthracycline-based chemotherapy-related nausea and emesis refractory to combination 5HT(3)-antagonist and dexamethasone. PATIENTS AND METHODS: Cancer patients with refractory emesis after their first cycle of doxorubicin-based chemotherapy were accrued into this study. Electroacupuncture was given during the second cycle of chemotherapy. Each patient was evaluated for the number of emetic episodes and grade of nausea within the first 24 hours after chemotherapy and electroacupuncture. RESULTS: Forty-seven of a total of 317 patients screened were eligible for this study. Of these, 27 patients agreed to participate. Twenty-six (26; 96.3%) of them had significant reduction in both nausea grade and episodes of vomiting after electroacupuncture. There was complete response with no emetic episodes in 37%. Subjectively, 25 (92.6%) of the total 27 patients believed that acupuncture was an acceptable procedure and was helpful in reducing emesis. Electroacupuncture was well-tolerated with a median pain score of 3 of 10. CONCLUSION: Electroacupuncture is well-tolerated and effective as an adjunct in reducing chemotherapy-related nausea and emesis.

Randomized double-blind trial of combined modality treatment with or without amifostine in unresectable stage III non-small-cell lung cancer.

PURPOSE: Greater toxicities have been recognized to be a consequence of combined chemotherapy and radiotherapy in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This study was designed to determine if the use of amifostine could reduce treatment-related toxicities associated with the use of paclitaxel plus carboplatin and thoracic radiotherapy. PATIENTS AND METHODS: Sixty patients with unresectable stage III NSCLC were treated with two cycles of paclitaxel 175 mg/m2 and carboplatin (area under the time-concentration curve = 6), followed by thoracic radiotherapy (64 Gy) with concurrent weekly paclitaxel 60 mg/m2. Patients were randomly assigned to receive 740 mg/m2 of amifostine (arm A) or placebo (arm B) before each dose of paclitaxel and carboplatin. Treatment-related toxicities were evaluated at each visit and nerve conduction tests were performed before and after treatment for the objective assessment of neurotoxicity. RESULTS: There was no significant difference between arms A and B in grade 3 to 4 neutropenia. In all 72 neurophysiological parameters measured, there was no significant difference between the two treatment arms, although there was a trend toward fewer patients showing deterioration in arm A for six of the parameters. Grade 2 to 3 esophagitis occurred in 43% of patients in arm A and in 70% of patients in arm B. The difference of -27% (95% confidence limit = -50%, 0.4%) was not statistically significant. Response rates and survival were also not significantly different between the two arms. CONCLUSION: Pretreatment with amifostine showed a trend toward reducing the severity of esophagitis associated with concurrent chemoradiotherapy, but it did not reach statistical significance. There was no significant protective effect on hematologic or neurologic toxicities induced by paclitaxel and carboplatin.

Concurrent chemoradiotherapy in locoregionally recurrent nasopharyngeal carcinoma.

PURPOSE: To analyze the results of concurrent chemoradiotherapy in patients with locoregional recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS: We performed a retrospective analysis of 35 patients with locoregional recurrent nasopharyngeal carcinoma referred to our department between March 1994 and November 2002. Most patients were male (77%), Chinese (97%), and had undifferentiated carcinoma (89%). Most had extensive locally recurrent Stage rT3-T4 disease (66%) with a median age at recurrence of 49 years (range, 35-69 years). A repeat course of radiotherapy was given concurrently with cisplatin, with cisplatin/5-fluorouracil as consolidation treatment. Significant morbidities were present, including cranial nerve palsies due to extensive recurrent local disease before treatment of the recurrence. RESULTS: The response rate to concurrent chemoradiotherapy was 58% (29% complete response and 29% partial response). The 5-year progression-free and overall survival rate, calculated using the Kaplan-Meier method, was 15% and 26%, respectively. Only 3 patients developed systemic metastases. Grade 3-4 acute toxicities included emesis (9%) and neutropenia (14%), and Grade 3-4 late toxicities consisted of temporal lobe necrosis (3%), cranial neuropathy (6%), and endocrine abnormalities (14%). CONCLUSION: Concurrent chemoradiotherapy is feasible in a selected group of patients with locoregional recurrent NPC, but the risk of major late toxicities is significant.

The impact of smoking status on the behavior and survival outcome of patients with advanced non-small cell lung cancer: a retrospective analysis.

STUDY OBJECTIVES: There are fundamental differences in characteristics between smokers and nonsmokers with non-small cell lung cancer (NSCLC). We aim to study the impact of smoking status on the behavior of the disease, and to identify differences in outcome between the two groups. DESIGN: A retrospective analysis was done of patients with NSCLC seen during the period from January 1999 to August 2002. Clinical characteristics, survival outcome, and response to treatment were reviewed and compared between the smokers and nonsmokers. SETTING: Department of Medical Oncology, National Cancer Center. RESULTS: Of 317 patients analyzed, 117 patients (36.3%) were nonsmokers. Among the nonsmokers, 74.5% had adenocarcinoma and 73.9% were women. The smokers had poorer performance status, reported more weight loss, and had a higher mean age at diagnosis of almost 8 years than nonsmokers. One hundred eighty-seven patients (59%) had died as of December 31, 2002. The nonsmokers had a longer median survival, although this was not statistically significant. There were no statistically significant differences in survival and response to chemotherapy between the two groups after adjusting for known prognostic factors. CONCLUSIONS: Despite the known differences in mutational spectra and clinical characteristics between smokers and nonsmokers with NSCLC, no differences in terms of response to chemotherapy and survival outcome were observed. This could imply that this disease is equally aggressive in these two groups. More research is needed to further delineate and characterize the differences between these two etiologically different forms of NSCLC.

Irinotecan and gemcitabine in patients with solid tumors: phase I trial.

Using a day 1 and 8, every-3-week schedule, our purpose was to determine the maximum tolerated dose of irinotecan (CPT-11, Camptosar) that can be administered immediately after gemcitabine (Gemzar) at a dose of 1,000 mg/m2 IV. In this phase I trial, the maximum tolerated dose was defined as the dose level immediately below the level in which two of the first three patients in any cohort, or at least two of six patients in any expanded cohort, experienced dose-limiting toxicity. Dose-limiting toxicity pertained only to toxicity during the first cycle of treatment. Escalation of irinotecan was planned in groups of three patients, with three additional patients added at the first indication of dose-limiting toxicity. A total of 19 patients have been enrolled. Grade 4 diarrhea was the dose-limiting toxicity at the irinotecan dose of 115 mg/m2. Hematologic toxicity was not dose limiting. Three patients required canceling of the day 8 dose due to grade 3 myelosuppression. Three patients, two with pancreatic cancer and one with metastatic carcinoma of unknown primary, had a partial response. The maximum tolerated dose of irinotecan in this combination was 100 mg/m2/dose. The dose-limiting toxicity was diarrhea. The maximum tolerated dose is the recommended starting dose for phase II studies.

Chemo-radiotherapy for stage III unresectable non-small cell lung cancer long-term results of a prospective study.

INTRODUCTION: Combined-modality treatment is considered standard of care in the treatment of stage III non-small-cell lung cancer (NSCLC). This study was designed to assess the efficacy and tolerability of induction paclitaxel/carboplatin followed by concurrent thoracic radiotherapy and weekly paclitaxel. MATERIALS AND METHODS: Patients with unresectable stage III NSCLC were treated prospectively with two cycles of paclitaxel (175 mg/m2) and carboplatin (area under the curve of 6) followed by radiotherapy (60-66 Gy) concurrent with 6 weekly doses of paclitaxel (60 mg/m2). Response was determined 8 weeks after the completion of treatment and treatment-related toxicities were assessed at each visit during treatment and follow-up. RESULTS: Sixty-three patients were treated, 5 had complete response and 33 had partial response, giving a response rate of 60%. Thirty-seven percent of patients developed grade 3 or 4 neutropenia; 48% had significant esophagitis requiring the use of narcotic analgesics. Two patients developed esophageal stricture subsequently. The median survival was 51 months and 12 months for stage IIIA and IIIB patients, respectively. Progression-free survival was 16 months and 11 months respectively. CONCLUSIONS: The response rate was encouraging. Esophagitis was a significant morbidity and should prompt modification of treatment regimen, either in the chemotherapy schedule or by adjusting the radiotherapy treatment planning.

Unilateral breast edema in two patients with malignant pleural effusion.

Unilateral breast edema usually signifies an underlying pathology of the breast and prompts extensive investigations for the purpose of an early treatment. Although breast edema has been reported with other systemic etiologies, it has not been described in patients with lung cancer. We report two cases of unilateral breast edema occurring in patients with non-small cell lung cancer and ipsilateral pleural effusion. Mammography and ultrasound of the breast both revealed increased interstitial density suggestive of fluid retention without any underlying masses. We performed a therapeutic pleurocentesis on one patient for symptomatic relief, and there was simultaneous improvement of the breast edema. We postulate a possible pathophysiology for the association between breast edema and malignant pleural effusion. The principle of management when one encounters similar cases would be to treat the underlying pleural effusion.

Aspirin and non-aspirin non-steroidal anti-inflammatory drug use and risk of lung cancer.

There is evidence that aspirin and non-aspirin non-steroidal anti-inflammatory drug (NSAID) have anti-carcinogenic properties, but their effect on lung cancer, in particular in never-smokers, is unclear. Information on past or current use of anti-inflammatory medication was obtained in 398 Chinese female primary lung cancer cases and 814 controls in a hospital-based study in Singapore. 65% of cases and 88% of controls were never-smokers. Controls were excluded if they had been admitted for conditions associated with aspirin or NSAID use (n=174). Regular aspirin use (twice a week or more, for a month or more) was associated with a reduced risk of lung cancer (adjusted odds ratio [OR] 0.50, 95% confidence intervals [95%CI] 0.31-0.81 in non-smokers; OR 0.38, 95%CI 0.16-0.93 in smokers). Regular use of non-aspirin NSAID, paracetamol, steroid creams and steroid pills was uncommon and no association with lung cancer was detected. Our results suggest that aspirin consumption may reduce lung cancer risk in Asian women and are consistent with current understanding of the role of cyclooxygenase in lung carcinogenesis.

A Phase II study of pazopanib in Asian patients with recurrent/metastatic nasopharyngeal carcinoma.

PURPOSE: Nasopharyngeal carcinoma is endemic in Asia and angiogenesis is important for growth and progression. We hypothesized that pazopanib would have antiangiogenic activity in nasopharyngeal carcinoma. EXPERIMENTAL DESIGN: A single arm monotherapy study of pazopanib in patients with WHO type II/III nasopharyngeal carcinoma who had metastatic/recurrent disease and failed at least one line of chemotherapy. A Simon's optimal 2-stage design was used. Patients with Eastern Cooperative Oncology Group (ECOG) 0-2 and adequate organ function were treated with pazopanib 800 mg daily on a 21-day cycle. The primary endpoint was clinical benefit rate (CR/PR/SD) achieved after 12 weeks of treatment. Secondary endpoints included toxicity and progression-free survival. Exploratory studies of dynamic-contrast enhanced computed tomography (DCE-CT) paired with pharmacokinetics (PK) of pazopanib was done. RESULTS: Thirty-three patients were accrued. Patients were ECOG 0-1 with median age of 50 years (range 36-68). There were 2 (6.1%) partial responses, 16 (48.5%) stable disease, 11 (33.3%) progressive disease, 4 (12.1%) were not evaluable for response. The clinical benefit rate was 54.5% (95% CI: 38.0-70.2). Ten patients (30.3%) received more than 6 cycles (4 months) of treatment and 7 (21.2%) had PR/SD that lasted at least 6 months. One patient each died from epistaxis and myocardial infarction. Common grade 3/4 toxicities included fatigue (15.2%), hand-foot syndrome (15.2%), anorexia (9.1%), diarrhea (6.1%), and vomiting (6.1%). Serial DCE-CT scans show significant reductions in tumor blood flow, permeability surface area product, and fractional intravascular blood volume. CONCLUSION: Pazopanib showed encouraging activity in heavily pretreated nasopharyngeal carcinoma with an acceptable toxicity profile.

Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS).

PURPOSE: The results of the Iressa Pan-Asia Study (IPASS), which compared gefitinib and carboplatin/paclitaxel in previously untreated never-smokers and light ex-smokers with advanced pulmonary adenocarcinoma were published previously. This report presents overall survival (OS) and efficacy according to epidermal growth factor receptor (EGFR) biomarker status. PATIENTS AND METHODS: In all, 1,217 patients were randomly assigned. Biomarkers analyzed were EGFR mutation (amplification mutation refractory system; 437 patients evaluable), EGFR gene copy number (fluorescent in situ hybridization; 406 patients evaluable), and EGFR protein expression (immunohistochemistry; 365 patients evaluable). OS analysis was performed at 78% maturity. A Cox proportional hazards model was used to assess biomarker status by randomly assigned treatment interactions for progression-free survival (PFS) and OS. RESULTS: OS (954 deaths) was similar for gefitinib and carboplatin/paclitaxel with no significant difference between treatments overall (hazard ratio [HR], 0.90; 95% CI, 0.79 to 1.02; P = .109) or in EGFR mutation-positive (HR, 1.00; 95% CI, 0.76 to 1.33; P = .990) or EGFR mutation-negative (HR, 1.18; 95% CI, 0.86 to 1.63; P = .309; treatment by EGFR mutation interaction P = .480) subgroups. A high proportion (64.3%) of EGFR mutation-positive patients randomly assigned to carboplatin/paclitaxel received subsequent EGFR tyrosine kinase inhibitors. PFS was significantly longer with gefitinib for patients whose tumors had both high EGFR gene copy number and EGFR mutation (HR, 0.48; 95% CI, 0.34 to 0.67) but significantly shorter when high EGFR gene copy number was not accompanied by EGFR mutation (HR, 3.85; 95% CI, 2.09 to 7.09). CONCLUSION: EGFR mutations are the strongest predictive biomarker for PFS and tumor response to first-line gefitinib versus carboplatin/paclitaxel. The predictive value of EGFR gene copy number was driven by coexisting EGFR mutation (post hoc analysis). Treatment-related differences observed for PFS in the EGFR mutation-positive subgroup were not apparent for OS. OS results were likely confounded by the high proportion of patients crossing over to the alternative treatment.

Impact of comorbidities on clinical outcomes in non-small cell lung cancer patients who are elderly and/or have poor performance status.

AIM: We evaluated the effect of comorbidities on clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) who have poor performance status (PS 2/3) and/or are elderly (≥70 years old). SUMMARIZED DESCRIPTION: The impact of age (<70 versus >70), PS, and comorbidity score - Cumulative Illness Rating Scale for Geriatrics (CIRS-G) on treatment response, toxicities, QOL and overall survival (OS) was analyzed using data from a completed phase II trial that randomly assigned patients with advanced NSCLC who had PS 2/3 and/or were aged ≥70 to receive gemcitabine (GEM), vinorelbine (VIN) or docetaxel (DOC). RESULTS: Data from records of 134 patients accrued during the trial were available for analysis. Eighty-eight patients (66%) were aged ≥70 years. 59 patients (67%) had PS of ECOG 0-2 and 29 patients (33%) had ECOG 3. In those aged ≥70, 53 (60%) had at least one comorbidity rated CIRS-G category 3/4 while those aged <70, 12 (26%) had at least one CIRS-G 3/4 comorbidity. Age, PS, and comorbidity scores had no significant association with PFS and QOL scores changes, although PS had marginal influence on OS (0.05

Lung cancer in Chinese women: evidence for an interaction between tobacco smoking and exposure to inhalants in the indoor environment.

BACKGROUND: Epidemiologic data suggest that Chinese women have a high incidence of lung cancer in relation to their smoking prevalence. In addition to active tobacco smoke exposure, other sources of fumes and airborne particles in the indoor environment, such as cooking and burning of incense and mosquito coils, have been considered potential risk factors for lung cancer. OBJECTIVES: We used a case-control study to explore effects of inhalants from combustion sources common in the domestic environment on lung cancer and their modification by active tobacco smoking. METHODS: We analyzed 703 primary lung cancer cases and 1,578 controls. Data on demographic background and relevant exposures were obtained by face-to-face interviews in the hospital. RESULTS: We observed a positive relationship with daily exposure to incense or mosquito coils and to cooking fumes only among smokers, and no association among lifetime nonsmokers. Interactions between smoking and frequency of cooking, or exposure to incense or mosquito coils were statistically significant and consistent with synergistic effects on lung cancer. The odds ratio (OR) comparing smokers without daily incense or mosquito coil exposure with nonsmokers without daily exposure was 2.80 [95% confidence interval (CI), 1.86-4.21], whereas the OR comparing smokers with daily exposure to the same referent group was 4.61 (95% CI, 3.41-6.24). In contrast, daily exposure to incense or mosquito coils was not associated with lung cancer among nonsmokers (OR = 0.91; 95% CI, 0.72-1.16). We observed the same pattern of associations for smokers without (OR = 2.31; 95% CI, 1.52-3.51) and with (OR = 4.50; 95% CI, 3.21-6.30) daily cooking exposure compared with nonsmokers, with no evidence of an association with daily cooking exposure among nonsmokers. CONCLUSION: Our results suggest that active tobacco smoking not only is an important risk factor for development of lung cancer, but also may cause smokers to be more susceptible to the risk-enhancing effects of other inhalants.