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1.  Metabolic Tumor Volume is an Independent Prognostic Factor in Patients Treated Definitively for Non–Small-Cell Lung Cancer 
Clinical lung cancer  2011;13(1):52-58.
Fluroine-18 flurodeoxyglucose positron emission tomography (FDG-PET) imaging is considered standard for Non-Small Cell Lung Cancer (NSCLC). A retrospective review of 61 patients with NSCLC showed that higher FDG-PET metabolic tumor volume portended worse outcomes overall and in a subset of patients treated definitively.
Purpose
Fluorine-18 flurodeoxyglucose positron emission tomography (FDG-PET) imaging has rapidly become the standard of care for staging patients with lung cancer. We evaluated the prognostic value of metabolic tumor volume (MTV), a measure of tumor burden on FDG-PET imaging, in patients with non–small-cell lung cancer (NSCLC) treated definitively.
Methods and Materials
A retrospective review identified 61 patients with NSCLC who underwent FDG-PET imaging for pretreatment staging. Metabolically active tumor regions were segmented on the PET scans semiautomatically to calculate the total body MTV. We determined the relationship of overall survival (OS) and progression-free survival (PFS) with MTV in the entire cohort, and in the subgroup treated definitively.
Results
The estimated median PFS and OS for the entire cohort were 11.1 months and 18.9 months. Higher MTV was significantly associated with worse OS (P = 0.00075) and PFS (P = 0.00077). For definitively treated patients, when MTV was analyzed as a binary value above or below the median value, 2-year PFS was 60% versus 39.7% (median PFS 34.9 vs. 11.9 months) and 2-year OS was 79.7% versus 33.3% (median OS 41.9 vs. 18.9 months), respectively (log-rank P = 0.12 for PFS and P = 0.066 for OS). When MTV was analyzed as a continuous variable, multivariate Cox proportional hazards analysis demonstrated a trend to worse PFS (hazard ratio [HR] = 1.31; P = 0.12) and significantly worse OS (HR = 1.53; P = 0.018) with increasing MTV after controlling for known prognostic variables.
Conclusion
Tumor burden as assessed by MTV yields prognostic information on survival beyond that of established prognostic factors in patients with NSCLC treated definitively.
doi:10.1016/j.cllc.2011.05.001
PMCID: PMC4296977  PMID: 21703935
PET-CT
2.  A Phase II First-Line Study of Gemcitabine, Carboplatin, and Bevacizumab in Advanced Stage Non-squamous Non-small Cell Lung Cancer 
Background
Bevacizumab improves responses and progression-free survival when added to first-line paclitaxel/carboplatin or cisplatin/gemcitabine for patients with advanced nonsquamous non-small cell lung cancer. This study was designed to evaluate toxicities and efficacy of gemcitabine/carboplatin/bevacizumab.
Methods
Patients with untreated advanced nonsquamous non-small cell lung cancer, with no evidence of brain metastases and not on anticoagulation were eligible. Patients received gemcitabine 1000 mg/m2 on days 1 and 8; carboplatin area under the curve 5 day 1; and bevacizumab 15 mg/kg day 1 every 3 weeks for up to six cycles. Bevacizumab was then continued every 3 weeks until disease progression or unacceptable toxicity.
Results
From July 2006 to December 2008, 48 patients were enrolled: 23 (48%) men, 25 (52%) women, and 19 (40%) never smokers. One patient never received therapy and is not included in the analysis. Median cycle number was 8 (1– 42) with 37 patients (78.7%) completing ≥4 cycles of three drugs. Dose reductions occurred in 34 (72.3%) patients. Grade 3/4 toxicities included neutropenia (47%/15%), thrombocytopenia (11%/15%), anemia (6%/0%), dyspnea (6%/2%), bacterial pneumonia (4%/0%), and hypertension (4%/2%). No neutropenic fevers occurred. One patient died of hemoptysis. Grade 3 bleeding occurred in three other patients. There were seven (14.9%) partial responses. Median time to first event (progression/death/toxicity requiring discontinuation) was 6.4 months (95% confidence interval: 4.8 –7.9 months). The median overall survival (OS) was 12.8 months (95% confidence interval: 10.0 –16.5). The OS is 57% at 1 year and 10% at 2 years.
Conclusions
Although perhaps skewed by a high proportion of nonsmokers and women, treatment with gemcitabine/carboplatin/bevacizumab has an acceptable toxicity profile with promising median OS despite a low response rate.
doi:10.1097/JTO.0b013e3181f1d23c
PMCID: PMC4241413  PMID: 20881641
Lung cancer; Non-small cell; Antiangiogenic agents
4.  An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage 
Nature medicine  2014;20(5):548-554.
Circulating tumor DNA (ctDNA) represents a promising biomarker for noninvasive assessment of cancer burden, but existing methods have insufficient sensitivity or patient coverage for broad clinical applicability. Here we introduce CAncer Personalized Profiling by deep Sequencing (CAPP-Seq), an economical and ultrasensitive method for quantifying ctDNA. We implemented CAPP-Seq for non-small cell lung cancer (NSCLC) with a design covering multiple classes of somatic alterations that identified mutations in >95% of tumors. We detected ctDNA in 100% of stage II–IV and 50% of stage I NSCLC patients, with 96% specificity for mutant allele fractions down to ~0.02%. Levels of ctDNA significantly correlated with tumor volume, distinguished between residual disease and treatment-related imaging changes, and provided earlier response assessment than radiographic approaches. Finally, we explored biopsy-free tumor screening and genotyping with CAPP-Seq. We envision that CAPP-Seq could be routinely applied clinically to detect and monitor diverse malignancies, thus facilitating personalized cancer therapy.
doi:10.1038/nm.3519
PMCID: PMC4016134  PMID: 24705333
5.  Review of the current targeted therapies for non-small-cell lung cancer 
The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer (NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor (EGFR), and crizotinib which targets anaplastic lymphoma kinase (ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review promising agents which may overcome resistance, including the EGFR T790M-targeted agents CO-1686 and AZD9291, and the ALK-targeted agents ceritinib (LDK378), AP26113, alectinib (CH/RO5424802), and others. Emerging therapies directed against other driver oncogenes in NSCLC including ROS1, HER2, and BRAF are covered as well. The identification of specific molecular targets in a significant fraction of NSCLC has led to the personalized deployment of many effective targeted therapies, with more to come.
doi:10.5306/wjco.v5.i4.576
PMCID: PMC4129523  PMID: 25302162
Lung cancer; Non-small cell lung cancer; Targeted therapies; Epidermal growth factor receptor; Epidermal growth factor receptor; Anaplastic lymphoma kinase; Anaplastic lymphoma kinase; Acquired resistance
6.  How Do Social Factors Explain Outcomes in Non–Small-Cell Lung Cancer Among Hispanics in California? Explaining the Hispanic Paradox 
Journal of Clinical Oncology  2013;31(28):3572-3578.
Purpose
Hispanics in the United States have lower age-adjusted mortality resulting from non–small-cell lung cancer (NSCLC) compared with non-Hispanic whites (NHWs). The purpose of this study was to evaluate individual, clinical, and neighborhood factors in survival among Hispanics with NSCLC.
Patients and Methods
We performed a retrospective analysis of NHWs and Hispanics with NSCLC between 1998 and 2007 in the California Cancer Registry (follow-up to December 2009). Kaplan-Meier curves depict survival by nativity for Hispanics with NSCLC. Cox proportional hazards models estimated hazard of mortality by race with adjustment for individual (age, sex, marital status), clinical (histologic grade, surgery, irradiation, chemotherapy), and neighborhood factors (neighborhood socioeconomic status, ethnic enclave).
Results
We included 14,280 Hispanic patients with NSCLC. Foreign-born Hispanics had 15% decreased risk of disease-specific mortality resulting from NSCLC compared with NHWs (hazard ratio [HR], 0.85; 95% CI, 0.83 to 0.88) after adjustment for individual, clinical, and neighborhood factors. After adjustment for individual factors, compared with US-born Hispanics, foreign-born Hispanics had 10% decreased risk of disease-specific mortality (HR, 0.90; 95% CI, 0.87 to 0.96). Clinical and neighborhood factors slightly moderated the survival benefit for foreign-born patients. A modestly more pronounced survival advantage was seen for foreign-born Hispanics living in low socioeconomic and high Hispanic enclave neighborhoods as compared with US-born Hispanics (HR, 0.86; 95% CI, 0.81 to 0.90).
Conclusion
Foreign-born Hispanics with NSCLC have a decreased risk of disease-specific mortality compared with NHWs and US-born Hispanics with NSCLC. Neighborhood factors slightly moderate this survival advantage. This survival advantage is slightly more pronounced in lower socioeconomic and higher Hispanic enclave neighborhoods.
doi:10.1200/JCO.2012.48.6217
PMCID: PMC3782149  PMID: 23960183
8.  Isolation and mutational analysis of circulating tumor cells from lung cancer patients with magnetic sifters and biochips† 
Lab on a chip  2014;14(1):78-88.
Detection and characterization of circulating tumor cells (CTCs) may reveal insights into the diagnosis and treatment of malignant disease. Technologies for isolating CTCs developed thus far suffer from one or more limitations, such as low throughput, inability to release captured cells, and reliance on expensive instrumentation for enrichment or subsequent characterization. We report a continuing development of a magnetic separation device, the magnetic sifter, which is a miniature microfluidic chip with a dense array of magnetic pores. It offers high efficiency capture of tumor cells, labeled with magnetic nanoparticles, from whole blood with high throughput and efficient release of captured cells. For subsequent characterization of CTCs, an assay, using a protein chip with giant magnetoresistive nanosensors, has been implemented for mutational analysis of CTCs enriched with the magnetic sifter. The use of these magnetic technologies, which are separate devices, may lead the way to routine preparation and characterization of “liquid biopsies” from cancer patients.
doi:10.1039/c3lc50580d
PMCID: PMC4144998  PMID: 23969419
10.  A double-blind randomized discontinuation phase II study of sorafenib (BAY 43-9006) in previously treated non-small cell lung cancer patients: Eastern Cooperative Oncology Group study E2501 
Introduction
Sorafenib is a raf kinase and angiogenesis inhibitor with activity in multiple cancers. This phase II study in heavily pretreated non-small cell lung cancer (NSCLC) patients (≥ two prior therapies) utilized a randomized discontinuation design.
Methods
Patients received 400 mg of sorafenib orally twice daily for two cycles (two months) (Step 1). Responding patients on Step 1 continued on sorafenib; progressing patients went off study, and patients with stable disease were randomized to placebo or sorafenib (Step 2), with crossover from placebo allowed upon progression. The primary endpoint of this study was the proportion of patients having stable or responding disease two months after randomization.
Results
: There were 299 patients evaluated for Step 1 with 81 eligible patients randomized on Step 2 who received sorafenib (n=50) or placebo (n=31). The two-month disease control rates following randomization were 54% and 23% for patients initially receiving sorafenib and placebo respectively, p=0.005. The hazard ratio for progression on Step 2 was 0.51 (95% CI 0.30, 0.87, p=0.014) favoring sorafenib. A trend in favor of overall survival with sorafenib was also observed (13.7 versus 9.0 months from time of randomization), HR 0.67 (95% CI 0.40-1.11), p=0.117. A dispensing error occurred which resulted in unblinding of some patients, but not before completion of the 8 week initial step 2 therapy. Toxicities were manageable and as expected.
Conclusions
: The results of this randomized discontinuation trial suggest that sorafenib has single agent activity in a heavily pretreated, enriched patient population with advanced NSCLC. These results support further investigation with sorafenib as a single agent in larger, randomized studies in NSCLC.
doi:10.1097/JTO.0b013e31826149ba
PMCID: PMC3444827  PMID: 22982658
NSCLC; sorafenib; randomized discontinuation trial
12.  Survival following non-small cell lung cancer among Asian/Pacific Islander, Latina, and non-Hispanic White women who have never smoked 
BACKGROUND
Lung cancer is the leading cause of cancer death among US Asian/Pacific Islander (API) and Latina women, despite low smoking prevalence. This study examined survival patterns following non-small cell lung cancer in a population-based sample of lung cancer cases from the San Francisco Bay Area Lung Cancer Study (SFBALCS).
METHODS
Women diagnosed with lung cancer from 1998–2003 and 2005–2008 and identified through the Greater Bay Area Cancer Registry were telephone-screened for eligibility for the SFBALCS. The screener data were linked to the cancer registry data to determine follow-up. This analysis included 187 non-Hispanic White, 23 US-born Latina, 32 foreign-born Latina, 30 US-born API, and 190 foreign-born API never smokers diagnosed with lung cancer and followed through 2008.
RESULTS
All-cause survival was poorer among APIs (hazard ratio (HR) and 95% confidence interval (CI) = 1.7 (1.0–2.8) among US-born APIs; 1.2 (0.9–1.5) among foreign-born APIs), and Latinas (HR (95% CI) = 2.1 (1.2–3.6) among US-born Latinas; 1.4 (0.9–2.3) among foreign-born Latinas), relative to non-Hispanic Whites. These survival differences were not explained by differences in selected sociodemographic or clinical factors.
CONCLUSIONS
Further research should focus on factors such as cultural behaviors, access to or attitudes toward health care, and genetic variations, as possible explanations for these striking racial/ethnic differences.
IMPACT
Latina and API female never smokers diagnosed with lung cancer were up to two-times more likely to die than non-Hispanic Whites, highlighting the need for additional research to identify the underlying reasons for the disparities, as well as heightened clinical awareness.
doi:10.1158/1055-9965.EPI-10-0965
PMCID: PMC3070404  PMID: 21239685
lung cancer survival; Asian; Latina; Hispanic; never smokers; nativity
13.  A phase I dose-escalation and pharmacokinetic study of enzastaurin and erlotinib in patients with advanced solid tumors 
Cancer Chemotherapy and Pharmacology  2011;69(4):1013-1020.
Purpose
Enzastaurin, an oral serine/threonine kinase inhibitor, targets the protein kinase C and AKT pathways with anti-tumor and anti-angiogenic effects. Erlotinib, an oral epidermal growth factor receptor (EGFR) inhibitor, has activity in solid tumors. Based on the promising combination of EGFR inhibitors and anti-angiogenic agents, this phase I trial was initiated.
Methods
This single-institution, open-label, non-randomized trial used a standard 3 + 3 dose-escalation model in patients with advanced solid malignancies including non-small-cell lung cancer (NSCLC). Two dose levels of enzastaurin (with loading doses) were explored: 250 mg daily and 500 mg daily. Erlotinib was given at 150 mg daily.
Results
Sixteen patients were enrolled in this study (median age, 64 years). Most patients were heavily pre-treated, female, and Caucasian and had NSCLC. The highest dose of enzastaurin, 500 mg daily, was tolerated with no unexpected adverse events and no alteration in the pharmacokinetics of either drug at this dose level. The mean clearance was 5.75 L/h for erlotinib and 53.8 L/h for enzastaurin. The most common possibly drug-related grade 3–4 adverse events included diarrhea (25.0%), neurologic symptoms (18.8%), and vomiting (18.8%). Activity was noted, with a partial response in one patient and prolonged disease stability for >12 cycles in three patients.
Conclusion
The combination of enzastaurin 500 mg daily and erlotinib 150 mg daily is well tolerated and does not alter the pharmacokinetics of the individual drugs, with clinical activity seen. A phase II trial of this combination has been initiated in patients with advanced-stage NSCLC.
doi:10.1007/s00280-011-1792-8
PMCID: PMC3313020  PMID: 22160298
Clinical trial; Enzastaurin; Erlotinib; Pharmacokinetics
14.  Lung Cancer Among Postmenopausal Women Treated With Estrogen Alone in the Women's Health Initiative Randomized Trial 
Background
In the Women's Health Initiative (WHI) randomized controlled trial, use of estrogen plus progestin increased lung cancer mortality. We conducted post hoc analyses in the WHI trial evaluating estrogen alone to determine whether use of conjugated equine estrogen without progestin had a similar adverse influence on lung cancer.
Methods
The WHI study is a randomized, double-blind, placebo-controlled trial conducted in 40 centers in the United States. A total of 10 739 postmenopausal women aged 50–79 years who had a previous hysterectomy were randomly assigned to receive a once-daily 0.625-mg tablet of conjugated equine estrogen (n = 5310) or matching placebo (n = 5429). Incidence and mortality rates for all lung cancers, small cell lung cancers, and non–small cell lung cancers in the two randomization groups were compared by use of hazard ratios (HRs) and 95% confidence intervals (CIs) that were estimated from Cox proportional hazards regression analyses. Analyses were by intention to treat, and all statistical tests were two-sided.
Results
After a mean of 7.9 years (standard deviation = 1.8 years) of follow-up, 61 women in the hormone therapy group were diagnosed with lung cancer compared with 54 in the placebo group (incidence of lung cancer per year = 0.15% vs 0.13%, respectively; HR of incidence = 1.17, 95% CI = 0.81 to 1.69, P = .39). Non–small cell lung cancers were of comparable number, stage, and grade in both groups. Deaths from lung cancer did not differ between the two groups (34 vs 33 deaths in estrogen and placebo groups, respectively; HR of death = 1.07, 95% CI = 0.66 to 1.72, P = .79).
Conclusion
Unlike use of estrogen plus progestin, which increased deaths from lung cancer, use of conjugated equine estrogen alone did not increase incidence or death from lung cancer.
doi:10.1093/jnci/djq285
PMCID: PMC2943522  PMID: 20709992
15.  Adjuvant Chemotherapy for Early Stage Non-Small Cell Lung Cancer 
For many years adjuvant chemotherapy has been a standard treatment after complete resection in malignancies such as breast and colon but only recently has its use become standard in early stage non-small cell lung cancer (NSCLC). Although surgery is regarded as the best possible treatment for early stage NSCLC, only 20–25% of patients have resectable disease at presentation. Despite optimal surgical treatment, 5-year survival rates for NSCLC remain 50–60% for stage IB, 40–50% for stage II, and 20–30% for stage III (Kohler et al., 2011; Siegel et al., 2011). Adjuvant chemotherapy provides additional survival benefit in resected NSCLC but questions remain as to how to select patients for therapy and which regimen is best. Other than work with tegafur/uracil in Japan, the positive adjuvant trials have all utilized a cisplatin backbone, but the drug(s) to pair with cisplatin are a matter of debate and will be discussed further in this manuscript.
doi:10.3389/fonc.2011.00045
PMCID: PMC3356017  PMID: 22655247
lung cancer; non-small cell; adjuvant; chemotherapy; early stage
16.  Estrogen Plus Progestin and Lung Cancer in Postmenopausal Women 
Lancet  2009;374(9697):1243-1251.
Background
In the post intervention period of the Women’s Health Initiative (WHI) clinical trial, estrogen plus progestin increased total cancer incidence and an adverse influence on lung cancer mortality was suggested.
Methods
We conducted post hoc analyses over the full follow-up period of the WHI randomized, placebo-controlled clinical trial evaluating daily conjugated equine estrogen (CEE, 0.625 mg) plus medroxyprogesterone acetate (MPA, 2.5 mg) influence on lung cancer incidence and mortality in 16,608 postmenopausal women.
Findings
After 5.6 years intervention and 2.4 years additional follow-up (mean), there were 109 lung cancers in the hormone group and 85 in the placebo group (hazard ratio (HR) 1.23, 95% confidence interval (CI), 0.92, 1.63, P=0.16). While the difference was not statistically significant, for non-small cell lung cancer a possible divergence emerged over time, with more diagnoses in the CEE plus MPA group (96 vs 72 cases, respectively, HR 1.28, 95% CI 0.94, 1.73, P=0.12) and these cancers were more commonly poorly differentiated and more commonly had distant metastasis. Deaths from lung cancer were significantly increased in the CEE plus MPA group (73 vs 40 deaths, respectively, HR 1.71, 95% CI 1.16, 2.52, P=0.01) as were deaths from non-small cell lung cancer (62 vs 31 deaths, respectively, HR 1.87, 95% CI 1.22, 2.88, P=0.004). Small cell lung cancer incidence and mortality was comparable between randomization groups.
Interpretation
Use of estrogen plus progestin did not increase lung cancer incidence but significantly increased deaths from lung cancer. The effect may primarily be through influence on non-small cell lung cancer outcome.
doi:10.1016/S0140-6736(09)61526-9
PMCID: PMC2995490  PMID: 19767090
17.  Uncovering disparities in survival after non-small-cell lung cancer among Asian/Pacific Islander ethnic populations in California 
Asians may have better survival after non-small-cell lung cancer (NSCLC) than non-Asians. However, it is unknown whether survival varies among the heterogeneous U.S. Asian/Pacific Islander (API) populations. Therefore, this study aimed to quantify survival differences among APIs with NSCLC. Differences in overall and disease-specific survival were analyzed in the California Cancer Registry among 16,577 API patients diagnosed with incident NSCLC between 1988 and 2007. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models with separate baseline hazards by disease stage. Despite better overall and disease-specific survival among APIs compared with non-Hispanic Whites, differences were evident across API populations. Among women, Japanese (overall survival HR=1.16, 95% CI=1.06–1.27) and APIs other than those in the six largest ethnic groups (“other APIs”; HR=1.19, 95% CI=1.07–1.33) had significantly poorer overall and disease-specific survival than Chinese. By contrast, South Asian women had significantly better survival than Chinese (HR=0.79, 95% CI=0.63–0.97). Among men, Japanese (HR=1.15, 95% CI=1.07–1.24), Vietnamese (HR=1.07, 95% CI=1.00–1.16), and other APIs (HR=1.18, 95% CI=1.08–1.28) had significantly poorer overall and disease-specific survival than Chinese. Other factors independently associated with poorer survival were lower neighborhood SES, involvement with a non-university-teaching hospital, unmarried status, older age, and earlier year of diagnosis. APIs have significant ethnic differences in NSCLC survival that may be related to disparate lifestyles, biology, and especially health care access or use. To reduce the nationwide burden of lung cancer mortality, it is critical to identify and ameliorate hidden survival disparities such as those among APIs.
doi:10.1158/1055-9965.EPI-09-0332
PMCID: PMC2764550  PMID: 19622719
non-small-cell lung cancer; survival; Asian Americans; Pacific Islanders; ethnic groups
18.  Lung cancer incidence in never-smokers 
Purpose
Lung cancer is a leading cause of cancer death worldwide. While smoking remains the predominant cause of lung cancer, lung cancer in never-smokers is an increasingly prominent public health issue. Data on this topic, particularly lung cancer incidence rates in never-smokers, however, are limited.
Methods
We review the existing literature on lung cancer incidence and mortality rates among never-smokers and present new data regarding rates in never-smokers from large, population-based cohorts: 1) Nurses’ Health Study, 2) Health Professionals Follow-up Study, 3) California Teachers Study, 4) Multiethnic Cohort Study, 5) Swedish Lung Cancer Register in the Uppsala/Örebro region, and the 6) First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study.
Results
Truncated age-adjusted incidence rates of lung cancer among never-smokers aged 40 to 79 years in these six cohorts ranged from 14.4 to 20.8 per 100,000 person-years in women and 4.8 to 13.7 per 100,000 person-years in men, supporting earlier observations that women are more likely than men to have non-smoking-associated lung cancer. The distinct biology of lung cancer in never-smokers is apparent in differential responses to epidermal growth factor receptor inhibitors and an increased prevalence of adenocarcinoma histology in never-smokers.
Conclusion
Lung cancer in never-smokers is an important public health issue needing further exploration of its incidence patterns, etiology, and biology.
doi:10.1200/JCO.2006.07.2983
PMCID: PMC2764546  PMID: 17290054
19.  Review of erlotinib in the treatment of advanced non-small cell lung cancer 
Biologics : Targets & Therapy  2007;1(4):335-346.
Epidermal growth factor receptor (EGFR) is a transmembrane receptor with a cytoplasmic tyrosine kinase (TK) domain present on many solid tumors including non-small cell lung cancer (NSCLC). Once stimulated by ligand, the downstream pathway is activated leading to cell growth, survival, and carcinogenesis. There are several methods of EGFR inhibition including monoclonal antibodies directed against the external region and small molecule inhibitors of TK domain. Erlotinib and gefitinib are orally available small molecule EGFR TK inhibitors, with proven efficacy in NSCLC. The most common side effects are skin toxicity and diarrhea. Erlotinib has been shown to improve survival compared to placebo in second or third-line therapy for NSCLC. However, erlotinib in combination with chemotherapy failed to show a survival advantage in two first-line studies which could be due to the timing of chemotherapy administration. In general, patients with adenocarcinoma histology, female gender, Asian ethnicity, and never smokers have a better response when treated with erlotinib. This could be related to the presence of EGFR mutations, lack of KRAS mutations, or overexpression of EGFR as measured by fluorescent in-situ hybridization (FISH) analysis. Future studies should concentrate on further development of predictors of clinical benefit with erlotinib, overcoming resistance to erlotinib that develops in initial responders, as well as more effective sequencing of erlotinib with chemotherapy and combinations of the drug with other “targeted” therapeutic agents.
PMCID: PMC2721286  PMID: 19707304
epidermal growth factor receptor; erlotinib; non-small cell lung cancer

Results 1-19 (19)