Ramaswamy Govindan

Publications (150)973.57 Total impact

• Article: A Phase I Trial of Sunitinib and Rapamycin in Patients with Advanced Non-Small Cell Lung Cancer.

  Saiama N Waqar, Priya K Gopalan, Kristina Williams, Siddhartha Devarakonda, Ramaswamy Govindan
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  ABSTRACT: Background: Sunitinib is an oral multitargeted tyrosine kinase inhibitor, with single-agent activity in non-small cell lung cancer (NSCLC). Resistance to tyrosine kinase inhibitor therapy is mediated by the mammalian target of rapamycin (mTOR) pathway, and may be reversed by using mTOR inhibitors. Methods: We performed a phase I study evaluating the combination of sunitinib and rapamycin in patients with advanced NSCLC. Results: Nineteen patients were enrolled in the study. The dose-limiting toxicities included infection, pneumonia, diarrhea/dehydration and treatment delay due to thrombocytopenia in 1 patient each. Sunitinib 25 mg orally daily and rapamycin 2 mg orally daily with 4 weeks on and 2 weeks off therapy were determined to be the maximum tolerated dose. No objective responses were noted, and 6 patients had stable disease as a best response. Conclusion: The combination of sunitinib and rapamycin is well-tolerated and warrants further investigation in the phase II setting.
  Chemotherapy 04/2013; 59(1):8-13. · 1.82 Impact Factor
• Article: Review of Ongoing Clinical Trials in Non-Small-Cell Lung Cancer: A Status Report for 2012 from the ClinicalTrials.gov Web Site.

  Janakiraman Subramanian, Thomas Regenbogen, Gayathri Nagaraj, Alex Lane, Siddhartha Devarakonda, Gongfu Zhou, Ramaswamy Govindan
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  ABSTRACT: INTRODUCTION:: Clinical research in non-small-cell lung cancer (NSCLC) is a rapidly evolving field. In an effort to identify the current trends in lung cancer clinical research, we reviewed ongoing clinical trials in NSCLC listed in the ClinicalTrials.gov registry in 2012, and we also compared this data to a similar survey conducted by us in 2009. METHODS:: The Web site's advanced search function was used to search for the term "non-small cell lung cancer." The search was further refined by using the following options from the search page drop-down menu, "open studies" and "interventional." Studies with non-NSCLC tumor histologies and pediatric studies were excluded. RESULTS:: Of the 477 trials included in the analysis, 105 (22.0%) were phase I, 223 phase II (46.8%), and 63 phase III trials (13.2%). When compared with data from 2009, university-sponsored trials decreased in number (45.4%-34.2%; p < 0.001) whereas industry-sponsored trials remained almost the same. There was a significant increase in trials conducted exclusively outside of the United States (35.9%-48.8%; p = 0.001). The number of studies with locations in China (61, 12.8%) was second only to that in the United States (244, 51.2%). Studies reporting biomarker analysis increased significantly from 37.5% to 49.1% in 2012 (p < 0.001). Biomarker-based patient selection also increased significantly from 7.9% to 25.8% (p < 0.001). Targeted therapies were evaluated in 70.6% of phase I/II and II trials, and the most common class of targeted agent studied was epidermal growth factor receptor tyrosine kinase inhibitors (38.0%). Prespecified accrual times were observed to increase when compared with data reported in 2009, especially among industry-sponsored studies. CONCLUSIONS:: Our survey identified major changes in lung cancer clinical research since 2009. Almost half of all studies registered at the ClinicalTrials.gov Web site are being conducted outside the United States, and several novel molecularly targeted agents are being evaluated in the treatment of patients with NSCLC. More importantly, we identified a threefold increase in the number of studies that perform biomarker testing to determine patient selection over the last 3 years.
  Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 03/2013; · 4.55 Impact Factor
• Article: Phase II Study of Docetaxel in Combination with Everolimus for Second- or Third-Line Therapy of Advanced Non-Small-Cell Lung Cancer.

  Suresh S Ramalingam, Taofeek K Owonikoko, Madhusmita Behera, Janakiraman Subramanian, Nabil F Saba, Scott A Kono, Anthony A Gal, Gabriel Sica, R Donald Harvey, Zhengjia Chen, Carmen M Klass, Dong M Shin, Haian Fu, Shi-Yong R Sun, Ramaswamy Govindan, Fadlo R Khuri
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  ABSTRACT: We conducted a phase II study of docetaxel in combination with everolimus, a mammalian target of rapamycin (mTOR) inhibitor, for salvage therapy of advanced non-small-cell lung cancer (NSCLC) based on promising preclinical and early-phase clinical data. Patients with advanced-stage NSCLC treated with one or two previous systemic therapy regimens were given docetaxel (60 mg/m) and everolimus (5 mg orally once daily on days 1-19) every 3 weeks. Archived tumor specimens were evaluated for markers of mTOR pathway activation (total and phosphorylated mTOR, Akt, S6, eIF4e, and 4EBP1). Twenty-eight patients were enrolled (median age: 62 years; male: 13; Caucasians: 19; adenocarcinoma: 20; performance status 0, 3; performance status 1, 23; 1 previous regimen, 16). A median of 3.5 cycles of therapy was administered. Two patients experienced partial response and 15 had stable disease (clinical benefit rate, 70%). The 6-month progression-free survival rate was 5%, and the median overall survival was 9.6 months. Low pAkt expression correlated with clinical benefit rate (p = 0.01) but not with progression-free survival or overall survival. The combination of everolimus and docetaxel was tolerated well, but the efficacy was relatively modest in an unselected population of patients with NSCLC.
  Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 03/2013; 8(3):369-72. · 4.55 Impact Factor
• Article: Prognostic impact of malignant pleural effusion at presentation in patients with metastatic non-small-cell lung cancer.

  Daniel Morgensztern, Saiama Waqar, Janakiraman Subramanian, Kathryn Trinkaus, Ramaswamy Govindan
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  ABSTRACT: : Despite its common occurrence, the influence of malignant pleural effusion (MPE) on the outcomes of patients with advanced non-small-cell lung cancer (NSCLC) with distant metastasis (M1b) is unknown. We evaluated the clinical characteristics associated with MPE at presentation and the prognostic impact of MPE at presentation in patients with stage M1b NSCLC. : We extracted data from the Surveillance Epidemiology and End Results (SEER) registry from patients with NSCLC diagnosed between 2004 and 2005. Odds-ratio estimates were calculated using logistic regression, and the Kaplan-Meier method was used to estimate the overall survival. Cox proportional hazard model was used to evaluate whether MPE was an independent risk for outcome. : Among the 57,685 patients, MPE was present in 9170 (15.9%), including 3944 out of 31,506 (12.5%) without distant metastases and 5226 (20.0%) out of 26,179 with M1b. The probability of MPE was higher in patients with larger tumors, mediastinal lymph node involvement, and adenocarcinoma, NSCLC not otherwise specified, or large-cell histology. In patients with stage M1b, median overall survival (3 months versus 5 months), estimated 1-year survival (12.6% versus 24.8%), and 2-year survival (5.4% versus 11.3%) were significantly lower in patients with MPE compared with those without MPE (hazards ratio 1.49, 95% confidence interval 1.44-1.54, p < 0.0001). MPE was also an independent factor for worse survival in multivariate analysis (hazards ratio 1.36, 95% confidence interval1.30-1.43, p < 0.001). : MPE is a common complication in patients with NSCLC and is associated with decreased survival in patients with distant metastases. If these data are validated, subsequent studies in patients with advanced NSCLC may consider stratification according to the MPE status.
  Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2012; 7(10):1485-9. · 4.55 Impact Factor
• Article: Prognostic Significance of Tumor Size in Patients with Stage III Non-Small-Cell Lung Cancer: A Surveillance, Epidemiology, and End Results (SEER) Survey from 1998 to 2003.

  Daniel Morgensztern, Saiama Waqar, Janakiraman Subramanian, Feng Gao, Kathryn Trinkaus, Ramaswamy Govindan
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  ABSTRACT: : Increased tumor size is a known risk for poor outcomes in patients with stage I and II non-small cell lung cancer (NSCLC), who are treated with surgery or radiotherapy. However, there is limited information regarding the impact of tumor size on the outcomes of patients with mediastinal lymph node involvement. We conducted a Surveillance, Epidemiology, and End Results (SEER) database analysis to evaluate the prognostic significance of tumor size in patients with unresected stage III NSCLC. : The SEER registry was queried for patients with unresected NSCLC stage III and no malignant pleural effusion, aged 21 years or older, and diagnosed between 1998 and 2003. Tumor size was defined as S1 (0.1-3cm), S2 (3.1-5cm), S3 (5.1-7cm), and S4 (7.1-20cm). Demographic variables included age, sex, race and histology. Overall survival (OS) and disease-specific survival (DSS) were estimated by the Kaplan-Meier method, and the Cox proportional hazard model was used to evaluate whether tumor size remained an independent risk factor in multivariable analysis. : A total of 12,315 patients met the eligibility criteria. Median age at diagnosis was 70 years and most patients were men (58.7%) and white (81.3%). Tumor size was an independent predictor for both OS (p < 0.0001) and DSS (p < 0.001) in all subgroups of patients. : Tumor size is an independent predictor for OS and DSS in patients with unresected stage III NSCLC, and should be considered in the stratification of patients treated in this setting after validation of this finding in additional studies.
  Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2012; 7(10):1479-84. · 4.55 Impact Factor
• Article: Genomic landscape of non-small cell lung cancer in smokers and never-smokers.

  Ramaswamy Govindan, Li Ding, Malachi Griffith, Janakiraman Subramanian, Nathan D Dees, Krishna L Kanchi, Christopher A Maher, Robert Fulton, Lucinda Fulton, John Wallis, [......], Jason Walker, Sandra McDonald, Ron Bose, David Ornitz, Donghai Xiong, Ming You, David J Dooling, Mark Watson, Elaine R Mardis, Richard K Wilson
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  ABSTRACT: We report the results of whole-genome and transcriptome sequencing of tumor and adjacent normal tissue samples from 17 patients with non-small cell lung carcinoma (NSCLC). We identified 3,726 point mutations and more than 90 indels in the coding sequence, with an average mutation frequency more than 10-fold higher in smokers than in never-smokers. Novel alterations in genes involved in chromatin modification and DNA repair pathways were identified, along with DACH1, CFTR, RELN, ABCB5, and HGF. Deep digital sequencing revealed diverse clonality patterns in both never-smokers and smokers. All validated EFGR and KRAS mutations were present in the founder clones, suggesting possible roles in cancer initiation. Analysis revealed 14 fusions, including ROS1 and ALK, as well as novel metabolic enzymes. Cell-cycle and JAK-STAT pathways are significantly altered in lung cancer, along with perturbations in 54 genes that are potentially targetable with currently available drugs.
  Cell 09/2012; 150(6):1121-34. · 32.40 Impact Factor
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  Article: Comprehensive genomic characterization of squamous cell lung cancers.

  Peter S Hammerman, D Neil Hayes, Matthew D Wilkerson, Nikolaus Schultz, Ron Bose, Andy Chu, Eric A Collisson, Leslie Cope, Chad J Creighton, Gad Getz, [......], Rileen Sinha, Andrey Sivachenko, Roman K Thomas, William D Travis, Ming-Sound Tsao, John N Weinstein, Dennis A Wigle, Stephen B Baylin, Ramaswamy Govindan, Matthew Meyerson
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  ABSTRACT: Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.
  Nature 09/2012; 489(7417):519-25. · 36.28 Impact Factor
• Article: Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer: a phase III trial.

  Giorgio V Scagliotti, Maciej Krzakowski, Aleksandra Szczesna, Janos Strausz, Anatoly Makhson, Martin Reck, Rafal F Wierzbicki, Istvan Albert, Michael Thomas, Jose Elias Abrao Miziara, Zsolt S Papai, Nina Karaseva, Sumitra Thongprasert, Elsa Dalmau Portulas, Joachim von Pawel, Ke Zhang, Paulina Selaru, Lesley Tye, Richard C Chao, Ramaswamy Govindan
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  ABSTRACT: Sunitinib plus erlotinib may enhance antitumor activity compared with either agent alone in non-small-cell lung cancer (NSCLC), based on the importance of the signaling pathways involved in tumor growth, angiogenesis, and metastasis. This phase III trial investigated overall survival (OS) for sunitinib plus erlotinib versus placebo plus erlotinib in patients with refractory NSCLC. Patients previously treated with one to two chemotherapy regimens (including one platinum-based regimen) for recurrent NSCLC, and for whom erlotinib was indicated, were randomly assigned (1:1) to sunitinib 37.5 mg/d plus erlotinib 150 mg/d or to placebo plus erlotinib 150 mg/d, stratified by prior bevacizumab use, smoking history, and epidermal growth factor receptor expression. The primary end point was OS. Key secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. In all, 960 patients were randomly assigned, and baseline characteristics were balanced. Median OS was 9.0 months for sunitinib plus erlotinib versus 8.5 months for erlotinib alone (hazard ratio [HR], 0.922; 95% CI, 0.797 to 1.067; one-sided stratified log-rank P = .1388). Median PFS was 3.6 months versus 2.0 months (HR, 0.807; 95% CI, 0.695 to 0.937; one-sided stratified log-rank P = .0023), and ORR was 10.6% versus 6.9% (two-sided stratified log-rank P = .0471), respectively. Treatment-related toxicities of grade 3 or higher, including rash/dermatitis, diarrhea, and asthenia/fatigue were more frequent in the sunitinib plus erlotinib arm. In patients with refractory NSCLC, sunitinib plus erlotinib did not improve OS compared with erlotinib alone, but the combination was associated with a statistically significantly longer PFS and greater ORR. The incidence of grade 3 or higher toxicities was greater with combination therapy.
  Journal of Clinical Oncology 05/2012; 30(17):2070-8. · 18.37 Impact Factor
• Article: Optimising therapy for EGFR-addicted NSCLC: just the start.

  Ramaswamy Govindan, Janakiraman Subramanian
  The lancet oncology 03/2012; 13(3):216-7. · 14.47 Impact Factor
• Article: A roundup of articles published in recent months.

  Janakiraman Subramanian, Saiama Waqar, Daniel Morgensztern, Ramaswamy Govindan
  Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 03/2012; 7(3):626-8. · 4.55 Impact Factor
• Article: MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer.

  Yan Lu, Ramaswamy Govindan, Liang Wang, Peng-yuan Liu, Boone Goodgame, Weidong Wen, Ananth Sezhiyan, John Pfeifer, Ya-fei Li, Xing Hua, Yian Wang, Ping Yang, Ming You
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  ABSTRACT: About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. MicroRNAs (miRNAs) are a class of small non-coding RNAs of 19-25 nt and play important roles in gene regulation in human cancers. The purpose of this study is to identify miRNA expression profiles that would better predict prognosis of stage I NSCLC. MiRNAs extracted from 527 stage I NSCLC patients were profiled on the human miRNA expression profiling v2 panel (Illumina). The expression profiles were analyzed for their association with cancer subtypes, lung cancer brain metastasis and recurrence/relapse free survival (RFS). MiRNA expression patterns between lung adenocarcinoma and squamous cell carcinoma differed significantly with 171 miRNAs, including Let-7 family members and miR-205. Ten miRNAs associated with brain metastasis were identified including miR-145*, which inhibit cell invasion and metastasis. Two miRNA signatures that are highly predictive of RFS were identified. The first contained 34 miRNAs derived from 357 stage I NSCLC patients independent of cancer subtype, whereas the second containing 27 miRNAs was adenocarcinoma specific. Both signatures were validated using formalin-fixed paraffin embedded and/or fresh frozen tissues in independent data set with 170 stage I patients. Our findings have important prognostic or therapeutic implications for the management of stage I lung cancer patients. The identified miRNAs hold great potential as targets for histology-specific treatment or prevention and treatment of recurrent disease.
  Carcinogenesis 03/2012; 33(5):1046-54. · 5.70 Impact Factor
• Article: Recent advances in lung cancer: summary of presentations from the 47 th annual meeting of the American Society of Clinical Oncology (ASCO) 2011.

  Janakiraman Subramanian, Saiama N Waqar, Daniel Morgensztern, Ramaswamy Govindan
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  ABSTRACT: In the last several years, we have made slow but steady progress in developing new treatment strategies for patients with lung cancer. The use of molecularly targeted therapy has made a significant impact on the outcomes of patients with lung cancer. Further research is ongoing to identify more effective ways to target lung cancer. In the recently concluded 47 th annual meeting of the American Society of Clinical Oncology, there were several presentations on novel targeted therapies for lung cancer, in addition to the effective and optimal use of existing cytotoxic and targeted therapies for lung cancer. For this review, we have selected presentations that primarily have an impact on clinical practice, and some presentations regarding emerging therapeutic agents.
  Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 01/2012; 7(1):260-5. · 4.55 Impact Factor
• Article: Malignant pleural mesothelioma.

  David S Ettinger, Wallace Akerley, Hossein Borghaei, Andrew Chang, Richard T Cheney, Lucian R Chirieac, Thomas A D'Amico, Todd L Demmy, Apar Kishor P Ganti, Ramaswamy Govindan, [......], Gregory A Otterson, Jyoti D Patel, Mary Pinder Schenck, Katherine M Pisters, Karen Reckamp, Gregory J Riely, Eric Rohren, Scott J Swanson, Douglas E Wood, Stephen C Yang
  Journal of the National Comprehensive Cancer Network: JNCCN 01/2012; 10(1):26-41. · 4.41 Impact Factor
• Article: Cancer gene sequencing: ethical challenges and promises.

  Siddhartha Devarakonda, Ramaswamy Govindan, Peter S Hammerman
  The virtual mentor : VM. 01/2012; 14(11):868-72.
• Article: Targeted and cytotoxic therapy in coordinated sequence (TACTICS): erlotinib, bevacizumab, and standard chemotherapy for non-small-cell lung cancer, a phase II trial.

  Ezra E W Cohen, Janakiraman Subramanian, Feng Gao, Livia Szeto, Mark Kozloff, Leonardo Faoro, Theodore Karrison, Ravi Salgia, Ramaswamy Govindan, Everett E Vokes
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  ABSTRACT: This trial focused on optimally combining existing targeted therapies and cytotoxic chemotherapy in the treatment of unselected patients with advanced non-small-cell lung cancer (NSCLC). Patients with previously untreated advanced-stage nonsquamous NSCLC were eligible for this trial. In module A, patients received up to 4 cycles of erlotinib 150 mg daily and bevacizumab 15 mg/kg every 3 weeks. Patients then received carboplatin (AUC = 6), paclitaxel 200 mg/m2, and bevacizumab 15 mg/kg for 4 cycles in module B. Patients who did not have progressive disease in module A received maintenance erlotinib 150 mg daily and bevacizumab 15 mg/kg every 3 weeks in module C. Forty-eight patients were enrolled in this multicenter phase II trial. Most patients were male (62.5%) and white (77.1%) with stage IV disease (93.8%) and adenocarcinoma histologic type (66.7%). The overall response rate in module A was 10.4%, in module B it was 15.1%, and in module C it was 5.5%. The study achieved its primary endpoint, with a nonprogression rate of 45.8% in module A. The median overall survival (OS) was 12.6 months. The novel systemic therapy regimen is feasible in patients with advanced NSCLC. However there is no further role for developing this regimen in unselected patients with NSCLC.
  Clinical Lung Cancer 11/2011; 13(2):123-8. · 2.94 Impact Factor
• Article: Targeted therapy in lung cancer: lessons learned from past experiences.

  Janakiraman Subramanian, Saiama N Waqar, Ramaswamy Govindan
  Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 11/2011; 6(11 Suppl 4):S1786-8. · 4.55 Impact Factor
• Article: Small cell lung cancer.

  Gregory P Kalemkerian, Wallace Akerley, Paul Bogner, Hossein Borghaei, Laura Chow, Robert J Downey, Leena Gandhi, Apar Kishor P Ganti, Ramaswamy Govindan, John C Grecula, [......], Leora Horn, Thierry M Jahan, Marianna Koczywas, Cesar A Moran, Harvey B Niell, Janis O'Malley, Jyoti D Patel, Neal Ready, Charles M Rudin, Charles C Williams
  Journal of the National Comprehensive Cancer Network: JNCCN 10/2011; 9(10):1086-113. · 4.41 Impact Factor
• Article: A phase II study of AT-101 (Gossypol) in chemotherapy-sensitive recurrent extensive-stage small cell lung cancer.

  Maria Q Baggstrom, Yingwei Qi, Marianna Koczywas, Athanassios Argiris, Elizabeth A Johnson, Michael J Millward, Sara C Murphy, Charles Erlichman, Charles M Rudin, Ramaswamy Govindan
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  ABSTRACT: AT-101 is an oral inhibitor of the antiapoptotic Bcl proteins (Bcl-2, Bcl-XL, Bcl-W, and Mcl-1) and an inducer of the pro-apoptotic proteins noxa and puma. We studied the efficacy of AT-101 in patients with recurrent chemosensitive extensive-stage small cell lung cancer (SCLC). Patients with recurrent "sensitive" SCLC (defined as no progression during and no disease recurrence <2 months after completion of first-line platinum-based chemotherapy) were eligible. AT-101 was administered 20 mg orally daily for 21 of 28 days each cycle for up to six cycles. The primary end point was the objective response rate. At the time of planned interim evaluation, none of the 14 evaluable patients enrolled in the first stage had any response to therapy, and the study was closed permanently for further accrual. Three patients (21%) achieved stable disease after two cycles of therapy. Grade 3 toxicities included anorexia, fatigue, and nausea/vomiting. AT-101 is not active in patients with recurrent chemosensitive SCLC.
  Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2011; 6(10):1757-60. · 4.55 Impact Factor
• Article: Hope without hype: EML4-ALK inhibition for treatment of lung cancer.

  Ramaswamy Govindan
  The lancet oncology 09/2011; 12(11):983-4. · 14.47 Impact Factor
• Article: Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small-cell lung cancer: Cancer and Leukemia Group B trial 30407.

  Ramaswamy Govindan, Jeffrey Bogart, Thomas Stinchcombe, Xiaofei Wang, Lydia Hodgson, Robert Kratzke, Jennifer Garst, Timothy Brotherton, Everett E Vokes
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  ABSTRACT: Cancer and Leukemia Group B conducted a randomized phase II trial to investigate two novel chemotherapy regimens in combination with concurrent thoracic radiation therapy (TRT). Patients with unresectable stage III non-small-cell lung cancer (NSCLC) were randomly assigned to carboplatin (area under the curve, 5) and pemetrexed (500 mg/m(2)) every 21 days for four cycles and TRT (70 Gy; arm A) or the same treatment with cetuximab administered concurrent only with TRT (arm B). Patients in both arms received up to four cycles of pemetrexed as consolidation therapy. The primary end point was the 18-month overall survival (OS) rate; if the 18-month OS rate was ≥ 55%, the regimen(s) would be considered for further study. Of the 101 eligible patients enrolled (48 in arm A and 53 in arm B), 60% were male; the median age was 66 years (range, 32 to 81 years); 44% and 35% had adenocarcinoma and squamous carcinoma, respectively; and more patients enrolled onto arm A compared with arm B had a performance status of 0 (58% v 34%, respectively; P = .04). The 18-month OS rate was 58% (95% CI, 46% to 74%) in arm A and 54% (95% CI, 42% to 70%) in arm B. No significant difference in OS between patients with squamous and nonsquamous NSCLC was observed (P = .667). The toxicities observed were consistent with toxicities associated with concurrent chemoradiotherapy. The combination of pemetrexed, carboplatin, and TRT met the prespecified criteria for further evaluation. This regimen should be studied further in patients with locally advanced unresectable nonsquamous NSCLC.
  Journal of Clinical Oncology 08/2011; 29(23):3120-5. · 18.37 Impact Factor