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Anne S Tsao,
Suyu Liu,
J Jack Lee,
Christine M Alden,
George R Blumenschein,
Roy Herbst,
Suzanne E Davis,
Edward Kim,
Scott Lippman,
John Heymach,
Hai Tran,
Ximing Tang,
Ignacio Wistuba,
Waun Ki Hong
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ABSTRACT: : The Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination trial prospectively obtained serum and tumor core biopsies and randomized 255 chemorefractory non-small-cell lung cancer (NSCLC) patients into four phase II trials: erlotinib, erlotinib-bexarotene, vandetanib, or sorafenib. Herein, we report the clinical and biomarker results of the phase II vandetanib trial.
: Fifty-four patients received vandetanib. The 8-week disease control rate was 33%, median progression-free survival (PFS) 1.81 months, and median overall survival (OS) 6.5 months. No demographic subgroups had PFS or OS benefit. Eight patients with EGFR mutations had a trend for higher 8-week disease control rate (63% versus 31%; p = 0.12) but worse OS (5.9 months versus 9 months; p = 0.8). Patients with EGFR gene amplification (n = 6) had a worse OS (3.9 months versus 9.5 months; p = 0.04). KRAS mutation patients (3.9 months versus 9.5 months; p = 0.23) also had a worse OS. For the serum biomarker analysis, patients with below the median serum expression of interleukin 9c (p = 0.019) and eotaxin (p = 0.007) had a shorter PFS. A trend toward a shorter PFS was also seen in patients with higher than the median neutrophil gelatinase-associated lipocalin (p = 0.079) and lower than the median TNF-related apoptosis-inducing ligand (p = 0.087).
: Our trial results are largely consistent with the literature in unselected pretreated NSCLC patients. Although vandetanib improved median PFS in EGFR mutation patients with epidermal growth factor receptor tyrosine kinase inhibitor-resistance compared with EGFR wild-type, there was no OS advantage. Although vandetanib is no longer in development in NSCLC, identification of a molecular phenotype that responds to dual epidermal growth factor receptor and vascular endothelial growth factor receptor inhibition would contribute to the field.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2013; 8(5):658-61. · 4.55 Impact Factor
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ABSTRACT: In recent years, the epidermal growth factor receptor (EGFR) family has become a key focus of non-small-cell lung cancer biology and targeted therapies, such as the reversible EGFR tyrosine kinase inhibitors erlotinib and gefitinib. Initially, response to these agents was associated with certain demographic and clinical characteristics; subsequently, it was discovered that these subgroups were more likely to harbor specific mutations in the EGFR gene that enhanced tumor response. However, the presence of these mutations does not equate to therapeutic success. Other aspects of EGFR family signaling, including other types of EGFR mutations, EGFR protein expression, EGFR gene amplification, mediators of downstream signaling, and other receptors with similar downstream pathways may all play a role in response or resistance to treatment. The identification of these and other molecular determinants is driving the development of novel therapies designed to achieve improved clinical outcomes in patients.
Clinical Lung Cancer 04/2013; · 2.94 Impact Factor
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ABSTRACT: INTRODUCTION:: We investigated safety, efficacy, and recurrence after postoperative hemithoracic intensity-modulated radiation therapy (IMRT) in patients with malignant pleural mesothelioma treated with extrapleural pneumonectomy (EPP), during the past decade at a single institution. METHODS:: In 2001-2011, 136 consecutive patients with malignant pleural mesothelioma underwent EPP with planned adjuvant IMRT. Eighty-six patients (64%) underwent hemithoracic IMRT; the rest were not eligible because of postoperative complications, disease progression, or poor performance status. We assessed toxicity, survival, and patterns of failure in these 86 patients. Toxicity was scored with the Common Terminology Criteria for Adverse Events version 4.0; survival outcomes were estimated with the Kaplan-Meier method; and locoregional patterns of failure were classified as in-field, marginal, or out-of-field. Risk factors related to survival were identified by univariate and multivariate Cox regression analysis. RESULTS:: Median overall survival time for all 86 patients receiving IMRT was 14.7 months. Toxicity rates of grade of 3 or more were: skin 17%, lung 12%, heart 2.3%, and gastrointestinal toxicity 16%. Five patients experienced grade 5 pulmonary toxicity. Rates of locoregional recurrence-free survival, distant metastasis-free survival, and overall survival (OS) were 88%, 55%, and 55% at 1 year and 71%, 40%, and 32% at 2 years. On multivariate analysis, pretreatment forced expiratory volume in 1 second, nonepithelioid histology, and nodal status were associated with distant metastasis-free survival and OS. CONCLUSION:: IMRT after EPP is associated with low rates of locoregional recurrence, though some patients experience life-threatening lung toxicity. Tumor histology and nodal status can be helpful in identifying patients for this aggressive treatment.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2012; · 4.55 Impact Factor
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Anne S Tsao,
Suyu Liu,
J Jack Lee,
Christine Alden,
George Blumenschein,
Roy Herbst,
Suzanne E Davis,
Edward Kim,
Scott Lippman,
David Stewart,
Xi Ming Tang,
Ignacio Wistuba,
Waun Ki Hong
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ABSTRACT: : Treating elderly non-small-cell lung cancer (NSCLC) patients in the salvage setting is challenging because of concerns of intolerance to therapy. Here we report outcomes (survival and toxicity) of elderly patients on the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial.
: Two hundred and fifty-five chemorefractory NSCLC patients received tumor molecular analysis, and were randomized to erlotinib, erlotinib-bexarotene, vandetanib, or sorafenib. Retrospective subgroup analyses were conducted comparing outcomes among age groups (< 65 versus ≥ 65 years; < 70 versus ≥ 70 years; < 75 versus ≥ 75 years), treatments, and sex.
: Median age was 62 years (range, 26-84); 38% were aged 65 years or more. No significant differences among age groups were seen in rates of biopsy-related pneumothorax, treatment-related death, compliance, grade 3 to 4 hematologic toxicities, response rate, nor overall survival. However, older women aged 65 years or more had more grade 3 to 4 nonhematologic toxicities (p = 0.05). Elderly men aged 65 years or more (p = 0.008) had a higher disease-control rate at 8 weeks and a better progression-free survival (PFS) (p = 0.0068). Elderly women aged 70 years or more had a trend toward higher 8-week disease-control rate (p = 0.06). Older men aged 65 years or more treated with vandetanib had a better median PFS (p = 0.03) whereas PFS of older women aged 70 years or more was worse (p = 0.03) compared with younger patients. Elderly men aged 70 years or more treated with sorafenib had a higher overall survival compared with younger men (p = 0.04). Tumor tissue biomarkers show distinct differences by sex and age.
: Fit elderly NSCLC patients should be considered for salvage targeted therapy. In this subset of patients, older men seem to have significant clinical benefit from certain agents. Tumor biomarker analysis demonstrates sex and age variations, and is hypothesis-generating.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2012; 7(11):1645-52. · 4.55 Impact Factor
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ABSTRACT: Persistent pathologic mediastinal nodal involvement after induction chemotherapy and surgical resection is a negative prognostic factor for stage III-N2 non-small cell lung cancer patients. This population has high rates of local-regional failure and distant failure, yet the effectiveness of additional therapies is not clear. We assessed the role of consolidative therapies (postoperative radiation therapy and chemotherapy) for such patients.
In all, 179 patients with stage III-N2 non-small cell lung cancer at MD Anderson Cancer Center were treated with induction chemotherapy followed by surgery from 1998 through 2008; 61 patients in this cohort had persistent, pathologically confirmed, mediastinal nodal disease, and were treated with postoperative radiation therapy. Local-regional failure was defined as recurrence at the surgical site or lymph nodes (levels 1 to 14, including supraclavicular), or both. Overall survival was calculated using the Kaplan-Meier method, and survival outcomes were assessed by log rank tests. Univariate and multivariate Cox proportional hazards models were used to identify factors influencing local-regional failure, distant failure, and overall survival.
All patients received postoperative radiation therapy after surgery, but approximately 25% of the patients also received additional chemotherapy: 9 (15%) with concurrent chemotherapy, 4 (7%) received adjuvant sequential chemotherapy, and 2 (3%) received both. Multivariate analysis indicated that additional postoperative chemotherapy significantly reduced distant failure (hazard ratio 0.183, 95% confidence interval: 0.052 to 0.649, p=0.009) and improved overall survival (hazard ratio 0.233, 95% confidence interval: 0.089 to 0.612, p=0.003). However, additional postoperative chemotherapy had no affect on local-regional failure.
Aggressive consolidative therapies may improve outcomes for patients with persistent N2 disease after induction chemotherapy and surgery.
The Annals of thoracic surgery 07/2012; 94(3):914-20. · 3.74 Impact Factor
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Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2011; 6(12):2144-2145. · 4.55 Impact Factor
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ABSTRACT: Malignant pleural mesothelioma (MPM) tumors express vascular epithelial growth factor (VEGF) and VEGF receptors. We conducted a phase II study of the oral pan-VEGF receptor tyrosine kinase inhibitor, cediranib, in patients with MPM after platinum-based systemic chemotherapy.
Patients with MPM previously treated with a platinum-containing chemotherapy regimen and a performance status 0 to 2 were eligible for enrollment. Cediranib 45 mg/d was administered until progression or unacceptable toxicity. The primary end point was response rate. Tumor measurements were made by RECIST criteria, with a subset analysis conducted using modified RECIST. A two-stage design with an early stopping rule based on response rate was used.
Fifty-four patients were enrolled. Of 47 evaluable patients, 4 patients (9%) had objective responses, 16 patients (34%) had stable disease, 20 patients (43%) had disease progression, 2 patients (4%) had symptomatic deterioration, and 1 patient (2%) had early death. The most common toxicities were fatigue (64%), diarrhea (64%), and hypertension (70%); 91% of patients required a dose reduction. Median overall survival was 9.5 months, 1-year survival was 36%, and median progression-free survival was 2.6 months.
Cediranib monotherapy has modest single-agent activity in MPM after platinum-based therapy. However, some patient tumors were highly sensitive to cediranib. This study provides a rationale for further testing of cediranib plus chemotherapy in MPM and highlights the need to identify a predictive biomarker for cediranib.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2011; 6(11):1938-45. · 4.55 Impact Factor
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Anne S Tsao,
Suyu Liu,
Junya Fujimoto,
Ignacio I Wistuba,
J Jack Lee,
Edith M Marom,
Chusilp Charnsangavej,
Frank V Fossella,
Hai T Tran,
George R Blumenschein,
Vassiliki Papadimitrakopoulou,
Merrill S Kies,
Waun K Hong,
David J Stewart
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ABSTRACT: Two phase II clinical trials in the aerodigestive tumors were undertaken to evaluate the efficacy of imatinib mesylate-docetaxel. We hypothesized that imatinib mesylate would inhibit platelet-derived growth factor receptor (PDGFR) on pericytes and increase docetaxel uptake into tumor cells for an additive antitumor effect. Baseline tumor specimens, serum, and perfusion computed tomography (CT) scans were obtained for supportive evaluation.
Eligible patients with metastatic non-small cell lung cancer (NSCLC) treated with 1 prior therapy and chemonaive patients with head and neck squamous cell carcinoma (HNSCC) were enrolled in separate trials, which administered both docetaxel (60 mg/m every 3 weeks) and oral imatinib mesylate (400 mg daily). Both trials used interim analyses for efficacy and safety.
Twenty-two patients with NSCLC and seven patients with HNSCC were enrolled. Both trials were closed early due to lack of efficacy, significant toxicity, and a potential antagonistic effect. In the NSCLC study, the response rate was 4.5%, median progression-free survival (PFS) 7.9 weeks, and overall survival 35.6 weeks. The HNSCC trial yielded a response rate 0%, PFS 8.8 weeks, and overall survival 34.7 weeks. Baseline NSCLC tumor immunohistochemical biomarker analyses indicated that lower expression of stromal PDGFRβ correlated with a better PFS, whereas stromal PDGFRα and tumor cell PDGFRβ were associated with a worse clinical outcome when treated with imatinib mesylate-docetaxel.
We do not recommend further investigation of this regimen in the aerodigestive tumors. Future investigations in PDGFR tyrosine kinase inhibitors should be used with caution in combination with taxanes and validation of the potential predictive or prognostic biomarkers stromal PDGFRα/β, and tumor cell PDGFRβ are needed.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2011; 6(12):2104-11. · 4.55 Impact Factor
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Oncology (Williston Park, N.Y.) 06/2011; 25(7):607, 614. · 1.03 Impact Factor
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ABSTRACT: Sarcomatoid non-small cell lung cancer (NSCLC) is an uncommon histologic variant that has not been molecularly well-characterized. We conducted immunohistochemical and fluorescence in situ hybridization studies of PDGF-B/PDGFR-b on archived surgically resected specimens and showed high PDGFR-b IHC expression and gene copy number gain. Further studies are warranted to determine whether PDGFR-b is a feasible therapeutic target in this population.
Sarcomatoid non-small cell lung cancer (NSCLC) is an uncommon histologic variant that has not been molecularly well-characterized. We hypothesized that the PDGF-B/PDGF-Rβ pathway may be dysregulated in sarcomatoid lung cancer.
We conducted immunohistochemical (IHC) and gene copy number gain studies of PDGF-B/PDGFR-β on archived surgically resected specimens, 43 sarcomatoid NSCLCs and 42 control NSCLCs that were age, gender and stage-matched. Biomarkers were correlated to patient demographics, tumor characteristics, and survival.
Sarcomatoid tumors had higher PDGFR-β IHC expression than control NSCLC (median score 2.69 vs. 1.93; P < 0.0001). No difference was seen between the two groups of PDGF-B IHC expression; and neither PDGF-B nor PDGFR-β IHC levels correlated with gender, age, clinical or pathologic TNM status, or overall survival. PDGFRB gene copy number was evaluated by FISH using three ways: presence of amplification, gene copy number gain, and gene copy ratio between tumor and normal tissue. PDGFRB gene copy number gain was associated with sarcomatoid histology (P = 0.006), lower clinical and pathologic T-stage (P = 0.07, P = 0.048), and higher pathologic N-stage (P = 0.013). Sarcomatoid NSCLC patients (P = 0.006) and female patients (P = 0.03) had higher gene copy ratios above 1.83. Higher PDGFR-β IHC expression in tumor cells was associated with gene copy number gain (P = 0.021) and higher gene copy ratio status (P = 0.005).
This is the first study to demonstrate high PDGFR-β IHC expression and gene copy number gain in sarcomatoid NSCLC tumors and suggests that further studies are warranted to determine whether PDGFR-β is a feasible therapeutic target in this population.
Clinical Lung Cancer 05/2011; 12(6):369-74. · 2.94 Impact Factor
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ABSTRACT: Malignant pleural mesothelioma (MPM) is difficult to measure radiographically due to the nonradial and variable pattern of growth and response to therapy. Inaccurate and inconsistent tumor measurements often compromise results from clinical trials that are dependent on identifying response rate and progression-free survival. In this article, we sought to provide a practical guide through the Southwest Oncology Group on how to measure MPM by the updated RECIST version 1.1 and by modified RECIST. We hope that these steps will provide a simple means by which computed tomography measurements can be consistently performed, minimizing intra- and interobserver variability. With this consistency, we may be able to better estimate the prognosis and response to therapy. With greater utilization, we will be able to better understand the biology of MPM.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 03/2011; 6(3):598-601. · 4.55 Impact Factor
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David P Carbone,
J Stuart Salmon,
Dean Billheimer,
Heidi Chen,
Alan Sandler,
Heinrich Roder,
Joanna Roder,
Maxim Tsypin,
Roy S Herbst, Anne S Tsao,
Hai T Tran,
Thao P Dang
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ABSTRACT: We applied an established and commercially available serum proteomic classifier for survival after treatment with erlotinib (VeriStrat) in a blinded manner to pretreatment sera obtained from recurrent advanced NSCLC patients before treatment with the combination of erlotinib plus bevacizumab. We found that VeriStrat could classify these patients into two groups with significantly better or worse outcomes and may enable rational selection of patients more likely to benefit from this costly and potentially toxic regimen.
Lung cancer (Amsterdam, Netherlands) 09/2010; 69(3):337-40. · 3.14 Impact Factor
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ABSTRACT: Patients with stage III non-small-cell lung cancer (nSclc) comprise a heterogeneous population; the role of surgical resection in this setting has been controversial. Albain and colleagues recently demonstrated that trimodality therapy with lobectomy had clinical benefit for patients with pathologic nodal N2 stage III nSclc. we discuss the trial and its implications for future lung cancer therapy.
Nature Reviews Clinical Oncology 01/2010; 7(1):10-2. · 11.96 Impact Factor
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Anne S Tsao,
Diane Liu,
Jack Martin,
Xi-ming Tang,
J Jack Lee,
Adel K El-Naggar,
Ignacio Wistuba,
Kirk S Culotta,
Li Mao,
Ann Gillenwater,
Yuko M Sagesaka,
Waun K Hong,
Vassiliki Papadimitrakopoulou
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ABSTRACT: Epidemiologic and preclinical data support the oral cancer prevention potential of green tea extract (GTE). We randomly assigned patients with high-risk oral premalignant lesions (OPL) to receive GTE at 500, 750, or 1,000 mg/m(2) or placebo thrice daily for 12 weeks, evaluating biomarkers in baseline and 12-week biopsies. The OPL clinical response rate was higher in all GTE arms (n = 28; 50%) versus placebo (n = 11; 18.2%; P = 0.09) but did not reach statistical significance. However, the two higher-dose GTE arms [58.8% (750 and 1,000 mg/m(2)), 36.4% (500 mg/m(2)), and 18.2% (placebo); P = 0.03] had higher responses, suggesting a dose-response effect. GTE treatment also improved histology (21.4% versus 9.1%; P = 0.65), although not statistically significant. GTE was well tolerated, although higher doses increased insomnia/nervousness but produced no grade 4 toxicity. Higher mean baseline stromal vascular endothelial growth factor (VEGF) correlated with a clinical (P = 0.04) but not histologic response. Baseline scores of other biomarkers (epithelial VEGF, p53, Ki-67, cyclin D1, and p16 promoter methylation) were not associated with a response or survival. Baseline p16 promoter methylation (n = 5) was associated with a shorter cancer-free survival. Stromal VEGF and cyclin D1 expression were downregulated in clinically responsive GTE patients and upregulated in nonresponsive patients at 12 weeks (versus at baseline). An extended (median, 27.5 months) follow-up showed a median time to oral cancer of 46.4 months. GTE may suppress OPLs, in part through reducing angiogenic stimulus (stromal VEGF). Higher doses of GTE may improve short-term (12-week) OPL outcome. The present results support longer-term clinical testing of GTE for oral cancer prevention.
Cancer Prevention Research 11/2009; 2(11):931-41. · 4.91 Impact Factor
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International journal of radiation oncology, biology, physics 11/2009; 75(2):326-37. · 4.59 Impact Factor
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ABSTRACT: Malignant pleural mesothelioma (MPM) is a deadly disease that occurs in 2,000 to 3,000 people each year in the United States. Although MPM is an extremely difficult disease to treat, with the median overall survival ranging between 9 and 17 months regardless of stage, there has been significant progress over the last few years that has reshaped the clinical landscape. This article will provide a comprehensive discussion of the latest developments in the treatment of MPM. We will provide an update of the major clinical trials that impact mesothelioma treatment in the resectable and unresectable settings, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. In addition, there are controversial issues, such as the role of extrapleural pneumonectomy, adjuvant radiotherapy, and use of intensity-modulated radiotherapy versus hemithoracic therapy that will also be addressed in this manuscript.
Journal of Clinical Oncology 04/2009; 27(12):2081-90. · 18.37 Impact Factor
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ABSTRACT: Historically, malignant pleural mesothelioma patients with potentially resectable disease have been treated with surgery and radiation alone. With improvements in systemic and intrapleural treatment options, a movement toward multi-modality therapy has become more common. Systemic treatment options largely consist of neoadjuvant chemotherapy with platinum doublets and most recently novel targeted agents, such as dasatinib. Intrapleural strategies have included injecting chemotherapy, chemotherapy with hyper thermic per fusion, gene therapy, and immunotherapy. The following review discusses the latest results in neoadjuvant and intrapleural therapies in malignant pleural mesothelioma.
Clinical Lung Cancer 02/2009; 10(1):36-41. · 2.94 Impact Factor
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ABSTRACT: Malignant pleural mesothelioma (MPM) is a deadly disease with few systemic treatment options. One potential therapeutic target, the non-receptor tyrosine kinase c-Src, causes changes in proliferation, motility, invasion, survival, and angiogenesis in cancer cells and may be a valid therapeutic target in MPM. To test this hypothesis, we determined the effects of c-Src inhibition in MPM cell lines and examined c-Src expression and activation in tissue samples. We analyzed four MPM cell lines and found that all expressed total and activated c-Src. Three of the four cell lines were sensitive by in vitro cytotoxicity assays to the c-Src inhibitor dasatinib, which led to cell cycle arrest and increased apoptosis. Dasatinib also inhibited migration and invasion independent of the cytotoxic effects, and led to the rapid and durable inhibition of c-Src and its downstream pathways. We used immunohistochemical analysis to determine the levels of c-Src expression and activation in 46 archived MPM tumor specimens. The Src protein was highly expressed in tumor cells, but expression did not correlate with survival. However, expression of activated Src (p-Src Y419) on the tumor cell membrane was higher in patients with advanced-stage disease; the presence of metastasis correlated with higher membrane (P = 0.03) and cytoplasmic (P = 0.04) expression of p-Src Y419. Lower levels of membrane expression of inactive c-Src (p-Src Y530) correlated with advanced N stage (P = 0.02). Activated c-Src may play a role in survival, metastasis, and invasion of MPM, and targeting c-Src may be an important therapeutic strategy.
Molecular Cancer Therapeutics 08/2007; 6(7):1962-72. · 5.23 Impact Factor
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Anne S Tsao,
Adam S Garden,
Merrill S Kies,
William Morrison,
Lei Feng,
J Jack Lee,
Fadlo Khuri,
Ralph Zinner,
Jeffery Myers,
Vassiliki Papadimitrakopoulou,
Jan Lewin,
Gary L Clayman,
K Kian Ang,
Bonnie S Glisson
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ABSTRACT: To investigate the feasibility of combining concomitant boost accelerated radiation with docetaxel and cisplatin and assess the regimen's toxicity, locoregional control rate, and survival in patients with locally advanced head and neck cancer (HNSCC).
Patients with stage III-IV HNSCC were eligible. Phase I included two schedules of docetaxel and cisplatin: arm 1, once per week during weeks 1 to 4; arm 2, every 21 days for weeks 1 and 4. Radiation consisted of 72 Gy in 42 fractions over 6 weeks (concomitant boost).
Twenty patients were enrolled in phase I. The arm 1 maximum-tolerated dose (MTD) was defined at docetaxel 15 mg/m2 and cisplatin 20 mg/m2 based on prolonged mucositis in 29% of patients. The initial dose level in arm 2 was above the MTD. In total, 52 patients were treated using the arm 1 regimen in phase II. Acute toxicity included grade 3 mucositis and dermatitis in 81% and 44% of patients. The 2-year locoregional control rate was 71%. The 2-year progression-free and overall survival rates were 61% and 65%. Median survival was 37.8 months. Late effects included feeding tube dependence in 17% of patients alive and free of disease.
Locoregional control, survival, and acute toxicity with this regimen were comparable with other trials utilizing taxanes and/or platins and concomitant conventional or altered fractionation radiation. Our data suggest that chemotherapy added to concomitant boost fractionation may increase rates of long-term feeding tube dependence. Phase III trials are needed to assess the contribution of concomitant boost fractionation to chemoradiotherapy.
Journal of Clinical Oncology 10/2006; 24(25):4163-9. · 18.37 Impact Factor
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ABSTRACT: The purpose of the current study was to determine whether smoking during chemotherapy or chemoradiation therapy for nonsmall cell lung cancer (NSCLC) affects treatment outcome.
The authors reviewed the medical records of patients with NSCLC (AJCC Stage III or IV) who were treated with frontline chemotherapy or chemoradiation therapy at the University of Texas M. D. Anderson Cancer Center between January 1993 and December 2002. Treatment type, response, progression-free survival, and overall survival (OS) were correlated with patient demographic characteristics, clinical features, and smoking habits at the time of diagnosis and during therapy.
Of 1370 patients who were eligible for analysis, 497 received chemoradiation therapy and 873 received chemotherapy. In the chemoradiation group, 6% of patients were never-smokers, 45% were former smokers, and 49% were current smokers. Multivariate analysis demonstrated no prognostic effect of smoking status on treatment response or OS rates in the chemoradiation therapy group. In the chemotherapy group, 16% of patients were never-smokers, 42% were former smokers, and 42% were current smokers; 20% of patients continued to smoke during therapy. Never-smokers had higher response rates (19% vs. 8% vs. 12%; P=.004) and lower rates of progressive disease (49% vs. 65% vs. 66%; P=.002) than former and current smokers, respectively. The OS rates were found to be higher among never-smokers (P<0001), women (P=.002), and those with a better Eastern Cooperative Oncology Group (ECOG) performance status (P<.0001). The multivariate Cox model indicated that with adjustment for age, gender, stage of disease, and ECOG performance status, the hazard ratio was 1.47 for former smokers (P=.003) and 1.55 for current smokers (P=.0004). Active smoking during therapy did not appear to impact outcome.
Never-smokers were found to have an improved outcome over smokers when treated with chemotherapy.
Cancer 06/2006; 106(11):2428-36. · 4.77 Impact Factor
