The effect of cardiovascular disease on the association between immune-related adverse events and overall survival.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7059-7059
Author(s):  
Ohad Oren ◽  
Julian R. Molina
Keyword(s):  
Lung Cancer ◽  
Cardiovascular Disease ◽  
Overall Survival ◽  
Survival Analysis ◽  
Adverse Events ◽  
Disease States ◽  
All Cause Mortality ◽  
Artery Disease ◽  
Competing Causes ◽  
The Individual

7059 Background: Preliminary data suggests that immune-related adverse events (irAEs) are associated with lower all-cause mortality, presumably due to improved anti-tumor responses. Investigations of large cohorts are needed to establish better understanding of that association. Methods: We reviewed the Mayo Clinic database for all patients who received an immune checkpoint inhibitor (ICI). The primary outcome was all-cause mortality. Descriptive and uni-variate analyses were generated. Results: Between March, 2010 and July, 2019, 3,326 patients received an ICI. The most common irAEs were colitis (287, 8.6%), pneumonitis (238, 7.2%) and hepatitis (227, 6.9%). A total of 933 (28.1%) patients developed at least 1 irAE and 176 (5.3%) patients experienced 2 or more irAEs. Survival analysis demonstrated an association between the number of irAEs and all-cause mortality (log-rank, P < 0.0001), a relationship which was maintained for the 3 most common cancer types (lung, melanoma, renal) and for the individual ICI agents. In patients with lung cancer, colitis (P = 0.04) but not pneumonitis (P = 0.83) was associated with improved overall survival. No association between irEA and all-cause mortality was demonstrated in patients with history of stroke (log-rank, P = 0.12), peripheral artery disease (PAD) (log-rank, P = 0.68) and obesity (log-rank, P = 0.18). In an analysis of pre-ICI body-mass index (BMI), an association between irAE and lower overall mortality was shown in patients with BMI < 30 (log-rank, P < 0.001) and not in those with higher BMIs (log-rank, P = 0.09). The presence of stroke, PAD and obesity were associated with higher all-cause mortality in a survival analysis (P < 0.001). The irAE-mortality association was not modulated by the presence hypertension (log-rank, P < 0.0001), diabetes mellitus (log-rank, P < 0.0001), or heart failure (log-rank, P = 0.006). Conclusions: The development of any irAE is associated with higher overall survival. The presence of numerous cardiovascular disease states neutralizes that association, likely a result of competing causes of mortality although interaction with immune or inflammatory pathways is possible. In addition, pneumonitis is not associated with better overall survival in patients with lung cancer presumably due to compromise of already-tenuous respiratory status.

scholarly journals All-cause mortality and location of death in patients with established cardiovascular disease before, during, and after the COVID-19 lockdown: a Danish Nationwide Cohort Study

2021 ◽  
Author(s):  
Jawad H Butt ◽  
Emil L Fosbøl ◽  
Thomas A Gerds ◽  
Charlotte Andersson ◽  
Kristian Kragholm ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Mortality Rate ◽  
Hospital Mortality ◽  
Location Of Death ◽  
All Cause Mortality ◽  
History Of ◽  
Adjusted Incidence Rate ◽  
Artery Disease ◽  
Adjusted Incidence ◽  
Overall Mortality

Abstract Background On 13 March 2020, the Danish authorities imposed extensive nationwide lockdown measures to prevent the spread of the coronavirus disease 2019 (COVID-19) and reallocated limited healthcare resources. We investigated mortality rates, overall and according to location, in patients with established cardiovascular disease before, during, and after these lockdown measures. Methods and results Using Danish nationwide registries, we identified a dynamic cohort comprising all Danish citizens with cardiovascular disease (i.e. a history of ischaemic heart disease, ischaemic stroke, heart failure, atrial fibrillation, or peripheral artery disease) alive on 2 January 2019 and 2020. The cohort was followed from 2 January 2019/2020 until death or 16/15 October 2019/2020. The cohort comprised 340 392 and 347 136 patients with cardiovascular disease in 2019 and 2020, respectively. The overall, in-hospital, and out-of-hospital mortality rate in 2020 before lockdown was significantly lower compared with the same period in 2019 [adjusted incidence rate ratio (IRR) 0.91, 95% confidence interval (CI) CI 0.87–0.95; IRR 0.95, 95% CI 0.89–1.02; and IRR 0.87, 95% CI 0.83–0.93, respectively]. The overall mortality rate during and after lockdown was not significantly different compared with the same period in 2019 (IRR 0.99, 95% CI 0.97–1.02). However, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during and after lockdown compared with the same period in 2019 (in-hospital, IRR 0.92, 95% CI 0.88–0.96; out-of-hospital, IRR 1.04, 95% CI1.01–1.08). These trends were consistent irrespective of sex and age. Conclusions Among patients with established cardiovascular disease, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during lockdown compared with the same period in the preceding year, irrespective of age and sex.

Overall Survival Analysis and Characterization of an EGFR Mutated Non-Small Cell Lung Cancer (NSCLC) Population

2018 ◽  
Vol 54 (1) ◽  
pp. 10-17
Author(s):  
Filipa Aguiar ◽  
Gabriela Fernandes ◽  
Henrique Queiroga ◽  
José Carlos Machado ◽  
Luís Cirnes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Mutated ◽  
Overall Survival Analysis

scholarly journals 803 Immune-related adverse events correlate with improved outcomes in patients with advanced non-small cell lung cancer treated with combinations of immune-checkpoint inhibitors and chemotherapy

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A840-A840
Author(s):  
Lindsey Shantzer ◽  
Sean Dougherty ◽  
Wendy Novicoff ◽  
John Melson ◽  
Daniel Reed ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung

BackgroundImmune checkpoint inhibitors (ICIs) have become the backbone of treatment for most driver-mutation negative, advanced non-small cell lung cancers. ICIs have been approved both as monotherapy and in combination with chemotherapy for front line management. While ICIs are generally regarded as well-tolerated, an unintended activation of the immune system can result in a variety of immune-related adverse events (irAEs), which can limit their use in severe cases. In patients with NSCLC treated with ICI monotherapy, the occurrence of an irAE and the development of multisystem irAEs have been associated with improved clinical outcomes, suggesting irAE occurrence could have prognostic implications.1–4 However, in patients treated with combination immunotherapy plus chemotherapy, the correlation between irAEs and survival has not been completely elucidated.MethodsWe conducted a retrospective chart review of 94 patients with advanced NSCLC treated with a combination of ICI plus chemotherapy between 2015 and 2021 to evaluate for a correlation between irAE occurrence and overall survival (OS). Patients were divided into two groups: those who experienced at least one irAE and those who did not experience an irAE. To account for immortal time bias, we conducted landmark analyses at 12 and 24 weeks. We additionally investigated the impact of multisystem irAEs on clinical outcomes and described the profile of irAEs observed at our institution.ResultsAmong the 94 evaluable patients identified in our population, 43.6% experienced at least one irAE. Of those patients who experienced an irAE, 26 (63.4%) experienced a single irAE, 9 (22.0%) experienced 2 irAEs, and 6 (14.6%) experienced 3 or more irAEs. The most commonly observed irAEs were dermatitis followed by pneumonitis and colitis. In our cohort, patients with at least one irAE had significantly longer median OS (16.8 mos vs 9.8 mos) compared to those who did not experience an irAE (HR 0.51, 95% CI 0.43–0.76, p=0.011) (figure 1). Landmark survival analyses at 12 and 24 weeks continued to support significant differences in median OS based on presence or absence of an irAE (HR 0.49, 95% CI 0.24–0.46, and HR 0.45, 95% CI 0.21–0.60 respectively). Among patients with at least one irAE, the subset of patients who experienced multiple irAEs had further improved median OS compared to those with a single irAE.ConclusionsIn patients with advanced NSCLC treated with combination ICI plus chemotherapy, the occurrence of an irAE is associated with improved overall survival.ReferencesTeraoka S, Fujimoto D, Morimoto T, et al. Early Immune-related adverse events and association with outcome in advanced non-small cell lung cancer patients treated with Nivolumab: a prospective cohort study. Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer 2017;12(12):1798–1805. doi:10.1016/j.jtho.2017.08.022.Ricciuti B, Genova C, De Giglio A, et al. Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis. Journal of Cancer Research and Clinical Oncology 2019;145(2):479–485. doi:10.1007/s00432-018-2805-3.Toi Y, Sugawara S, Kawashima Y, et al. Association of immune-related adverse events with clinical benefit in patients with advanced non-small-cell lung cancer treated with nivolumab. The Oncologist. 2018;23(11):1358–1365. doi:10.1634/theoncologist.2017-0384.Shankar B, Zhang J, Naqash AR, et al. Multisystem immune-related adverse events associated with immune checkpoint inhibitors for treatment of non-small cell lung cancer. JAMA Oncol 2020;6(12):1952–1956. doi:10.1001/jamaoncol.2020.5012Ethics ApprovalThis research study obtained ethics approval by the institutional review board at the University of Virginia, IRB# 19083.Abstract 803 Figure 1Overall Survival by presence or absence of an irAE in patients with advanced lung cancer treated with immune checkpoint inhibitors plus chemotherapy

Overall Survival Analysis and Characterization of an EGFR Mutated Non-Small Cell Lung Cancer (NSCLC) Population

2018 ◽  
Vol 54 (1) ◽  
pp. 10-17 ◽  
Author(s):  
Filipa Aguiar ◽  
Gabriela Fernandes ◽  
Henrique Queiroga ◽  
José Carlos Machado ◽  
Luís Cirnes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Mutated ◽  
Overall Survival Analysis

scholarly journals Phase II study of α-galactosylceramide-pulsed antigen-presenting cells in patients with advanced or recurrent non-small cell lung cancer

2020 ◽  
Vol 8 (1) ◽  
pp. e000316 ◽  
Author(s):  
Takahide Toyoda ◽  
Toshiko Kamata ◽  
Kazuhisa Tanaka ◽  
Fumie Ihara ◽  
Mariko Takami ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Immune Responses ◽  
Survival Time ◽  
Phase Ii ◽  
Small Cell ◽  
Small Cell Lung ◽  
Inkt Cells ◽  
Antigen Presenting

BackgroundInvariant natural killer T (iNKT) cells produce copious amounts of cytokines in response to specific glycolipid antigens such as α-galactosylceramide (αGalCer) presented by CD1d-expressing antigen-presenting cells (APCs), thus orchestrating other immune cells to fight tumors. Because of their ability to induce strong antitumor responses activated by αGalCer, iNKT cells have been studied for their application in cancer immunotherapy. In our previous phase I/II trial in non-small cell lung cancer (NSCLC) patients who had completed the standard treatment, we showed a relatively long median survival time without severe treatment-related adverse events. Based on these results, we performed a phase II trial to evaluate clinical responses, safety profiles and immune responses as a second-line treatment for advanced NSCLC.MethodsPatients with advanced or recurrent NSCLC refractory to first-line chemotherapy were eligible. αGalCer-pulsed APCs were intravenously administered four times. Overall survival time was evaluated as the primary endpoint. The safety profile and immune responses after APC injection were also monitored. This study was an open label, single-arm, phase II clinical trial performed at Chiba University Hospital, Japan.ResultsThirty-five patients were enrolled in this study, of which 32 (91.4%) completed the trial. No severe adverse events related to the treatment were observed. The estimated median survival time of the 35 cases was 21.9 months (95% CI, 14.8 to 26.0). One case (2.9%) showed a partial response, 14 cases (40.0%) remained as stable disease, and 19 cases (54.3%) were evaluated as progressive disease. The geometric mean number of iNKT cells in all cases was significantly decreased and the mean numbers of natural killer (NK) cells, interferon-γ-producing cells in response to αGalCer, and effector CD8+ T cells were significantly increased after the administration of αGalCer-pulsed APCs.ConclusionsThe intravenous administration of αGalCer-pulsed APCs was well-tolerated and was accompanied by prolonged overall survival. These results are encouraging and warrant further evaluation in a randomized phase III trial to demonstrate the survival benefit of this immunotherapy.Trial registration numberUMIN000007321.

Association between hospital volume and overall survival of patients with metastatic non-small cell lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9044-9044 ◽  
Author(s):  
Gaurav Goyal ◽  
Adam C. Bartley ◽  
Ronald S. Go
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Small Cell Lung ◽  
Risk Of Death ◽  
All Cause Mortality ◽  
Lower Volume

9044 Background: Prior studies have shown superior surgical outcomes of stage I-III non-small cell lung cancer (NSCLC) in centers with higher patient volumes. However, there is a lack of such information in stage IV NSCLC. In this study, we aim to determine the association between the number of patients with stage IV NSCLC treated annually at a treatment facility (volume) and all-cause mortality (outcome). Methods: Using the National Cancer Database, we identified patients diagnosed with stage IV NSCLC between 2004 and 2013. We classified the facilities by quartiles (Q; mean patients with NSCLC treated per year): Q1: < 13.8; Q2: 13.8 to 23.6, Q3: 23.6 to 30.3, and Q4: > 30.3. We used sandwich variance estimators to account for clustering of patients within facilities and Cox regression to determine the volume-outcome relationship, adjusting for demographic (sex, age, race), socioeconomic (insurance type), receipt of chemotherapy, and comorbid (Charlson-Deyo score) factors and year of diagnosis. Results: There were 281,654 patients with stage IV NSCLC treated at 1,275 facilities. The median age at diagnosis was 66 years, and 55.7% were men. The median annual facility volume was 23.6 patients per year (range, 1.0 to 301.4). The distribution of patients according to facility volume was: Q1: 6.6%, Q2: 14.9%, Q3: 25.4%, and Q4: 53.1%. The unadjusted median overall survival by facility volume was: Q1: 4.4 months, Q2: 4.5 months, Q3: 4.7 months, and Q4: 5.3 months ( P< .001). Multivariable analysis showed that facility volume was independently associated with all-cause mortality. Compared with patients treated at Q4 facilities, patients treated at lower-quartile facilities had a small but significantly higher risk of death (Q3 hazard ratio [HR], 1.05 [95% CI, 1.03 to 1.07]; Q2 HR, 1.06 [95% CI, 1.03 to 1.09]; Q1 HR, 1.09 [95% CI, 1.06 to 1.13]). Conclusions: Patients who were treated for stage IV NSCLC at lower-volume facilities had a significantly higher risk of all-cause mortality compared with those who were treated at lower-volume facilities. [Table: see text]

NIVORAD: A randomised phase 2 trial of nivolumab and stereotactic ablative body radiotherapy in advanced non-small cell lung cancer, progressing after first or second line chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS9097-TPS9097 ◽  
Author(s):  
Paul Mitchell ◽  
Shankar Siva ◽  
Peey Sei Kok ◽  
Ken O'Byrne ◽  
Annie Yeung ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
New Zealand ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Stereotactic Ablative Body Radiotherapy

TPS9097 Background: Recent data has demonstrated improvements in overall survival in patients with advanced non-small cell lung cancer (NSCLC) treated with nivolumab. Radiation may augment the immune response through abscopal effects - evidence of tumour control at sites other than those irradiated. We hypothesize that the addition of stereotactic ablative body radiotherapy (SABR) to immunotherapy with nivolumab will improve progression free survival (PFS) compared with nivolumab alone. Methods: DESIGN: Open label, randomised phase II trial with 25 sites across Australia and New Zealand. ELIGIBILITY: Metastatic NSCLC progressing after 1 or 2 lines of chemotherapy with an extrapulmonary metastasis suitable for SABR. STRATIFICATION: Age, lines of chemotherapy, histology and treating institution. TREATMENT: A single dose of SABR (18-20Gy) plus nivolumab or nivolumab alone (240mg 2-weekly) given until disease progression or prohibitive adverse events. ENDPOINTS: PFS at 6 months (PFS6; primary), objective tumour response rate, adverse events, overall survival, PFS at 1 and 2 years. Tertiary correlative objectives include associations between possible prognostic/ predictive biomarkers and outcomes (including PD-L1 expression). STATISTICS:Total sample size of 120 participants allocated in a ratio of 2:1, 80 to nivolumab + SABR and 40 nivolumab alone to provide 80% power, one-sided type I error rate of 5% for PFS6 of 50% (worthy of pursuit) vs 35% (not worthy of pursuit). BIOSPECIMENS: Tumour tissue and serial bloods (4 time points) will be collected for translational research. CURRENT ENROLLMENT (as of Feb 2017): 2 out of 20 sites are open. NIVORAD is an investigator-initiated, cooperative-group trial led by the ALTG in collaboration with the NHMRC Clinical Trials Centre, University of Sydney and the Trans Tasman Radiation Oncology Group (TROG). Australian New Zealand Clinical Trials Registry: ACTRN12616000352404.

scholarly journals Effects of adding ivabradine to usual care in patients with angina pectoris: a systematic review of randomised clinical trials with meta-analysis and Trial Sequential Analysis

Open Heart ◽  
2020 ◽  
Vol 7 (2) ◽  
pp. e001288
Author(s):  
Mathias Maagaard ◽  
Emil Eik Nielsen ◽  
Naqash Javaid Sethi ◽  
Liang Ning ◽  
Si-hong Yang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Angina Pectoris ◽  
Adverse Events ◽  
Sequential Analysis ◽  
Randomised Clinical Trials ◽  
Trial Sequential Analysis ◽  
Serious Adverse Events ◽  
All Cause Mortality ◽  
Artery Disease

ObjectiveTo determine the impact of ivabradine on outcomes important to patients with angina pectoris caused by coronary artery disease.MethodsWe conducted a systematic review. We included randomised clinical trials comparing ivabradine versus placebo or no intervention for patients with angina pectoris due to coronary artery disease published prior to June 2020. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Cochrane methodology, Trial Sequential Analysis, Grading of Recommendations Assessment, Development, and Evaluation, and our eight-step procedure. Primary outcomes were all-cause mortality, serious adverse events and quality of life.ResultsWe included 47 randomised clinical trials enrolling 35 797 participants. All trials and outcomes were at high risk of bias. Ivabradine compared with control did not have effects when assessing all-cause mortality (risk ratio [RR] 1.04; 95% CI 0.96 to 1.13), quality of life (standardised mean differences −0.05; 95% CI −0.11 to 0.01), cardiovascular mortality (RR 1.07; 95% CI 0.97 to 1.18) and myocardial infarction (RR 1.03; 95% CI 0.91 to 1.16). Ivabradine seemed to increase the risk of serious adverse events after removal of outliers (RR 1.07; 95% CI 1.03 to 1.11) as well as the following adverse events classified as serious: bradycardia, prolonged QT interval, photopsia, atrial fibrillation and hypertension. Ivabradine also increased the risk of non-serious adverse events (RR 1.13; 95% CI 1.11 to 1.16). Ivabradine might have a statistically significant effect when assessing angina frequency (mean difference (MD) 2.06; 95% CI 0.82 to 3.30) and stability (MD 1.48; 95% CI 0.07 to 2.89), but the effect sizes seemed minimal and possibly without any relevance to patients, and we identified several methodological limitations, questioning the validity of these results.ConclusionOur findings do not support that ivabradine offers significant benefits on patient important outcomes, but rather seems to increase the risk of serious adverse events such as atrial fibrillation and non-serious adverse events. Based on current evidence, guidelines need reassessment and the use of ivabradine for angina pectoris should be reconsidered.PROSPERO registration numberCRD42018112082.

scholarly journals Improvement in VO2peak predicts readmissions for cardiovascular disease and mortality in patients undergoing cardiac rehabilitation

2019 ◽  
Vol 27 (8) ◽  
pp. 811-819 ◽  
Author(s):  
Nicolai Mikkelsen ◽  
Carmen Cadarso-Suárez ◽  
Oscar Lado-Baleato ◽  
Carla Díaz-Louzao ◽  
Carlos P Gil ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiac Rehabilitation ◽  
Cox Regression ◽  
State Model ◽  
Cardiac Rehabilitation Programme ◽  
All Cause Mortality ◽  
Long Term Follow Up ◽  
Artery Disease

Background Improvement in exercise capacity is a main goal of cardiac rehabilitation but the effects are often lost at long-term follow-up and thus also the benefits on prognosis. We assessed whether improvement in VO2peak during a cardiac rehabilitation programme predicts long-term prognosis. Methods and results We performed a retrospective analysis of 1561 cardiac patients completing cardiac rehabilitation in 2011–2017 in Copenhagen. Mean age was 63.6 (11) years, 74% were male and 84% had coronary artery disease, 6% chronic heart failure and 10% heart valve replacement. The association between baseline VO2peak and improvement after cardiac rehabilitation and being readmitted for cardiovascular disease and/or all-cause mortality was assessed with three different analyses: Cox regression for the combined outcome, for all-cause mortality and a multi-state model. During a median follow-up of 2.3 years, 167 readmissions for cardiovascular disease and 77 deaths occurred. In adjusted Cox regression there was a non-linear decreasing risk of the combined outcome with higher baseline VO2peak and with improvement of VO2peak after cardiac rehabilitation. A similar linear association was seen for all-cause mortality. Applying the multi-state model, baseline VO2peak and change in VO2peak were associated with risk of a cardiovascular disease readmission and with all-cause mortality but not with mortality in those having an intermediate readmission for cardiovascular disease. Conclusion VO2peak as well as change in VO2peak were highly predictive of future risk of readmissions for cardiovascular disease and all-cause mortality. The predictive value did not extend beyond the next admission for a cardiovascular event.

Phase I/IIa Study of Cetuximab With Gemcitabine Plus Carboplatin in Patients With Chemotherapy-Naïve Advanced Non–Small-Cell Lung Cancer

2005 ◽  
Vol 23 (36) ◽  
pp. 9089-9096 ◽  
Author(s):  
Francisco Robert ◽  
George Blumenschein ◽  
Roy S. Herbst ◽  
Frank V. Fossella ◽  
Jennifer Tseng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Tumor Response ◽  
Response Rate ◽  
Small Cell ◽  
Toxicity Profile ◽  
Time To Progression ◽  
Small Cell Lung ◽  
Grade 3

Purpose This multicenter, open-label, phase I/IIa study was undertaken to establish the safety/toxicity profile of cetuximab in combination with gemcitabine and carboplatin in patients with chemotherapy-naïve, epidermal growth factor receptor–positive, stage IV non–small-cell lung cancer. Secondary objectives were to gather preliminary evidence of efficacy including tumor response rate, time to progression, and overall survival. Patients and Methods Thirty-five patients received a total of 264 3-week cycles of treatment with cetuximab, carboplatin, and gemcitabine. An initial dose of cetuximab 400 mg/m2 intravenously was administered the first week, followed by weekly doses of 250 mg/m2. Carboplatin (area under the curve = 5, day 1) and gemcitabine 1,000 mg/m2 on days 1 and 8 were administered every 3 weeks. Patients were evaluated for tumor response after every two cycles of therapy. Results The most frequently reported adverse events related to cetuximab included an acne-like rash (88.6%), dry skin (34.3%), asthenia and skin disorders (31.4%), mucositis/stomatitis (25.7%), fever/chills (20%), and nausea/vomiting (17.1%). The majority of these toxicities were mild to moderate. One patient withdrew from the study because of a grade 3 allergic reaction. Myelosuppression was the most frequently observed toxicity related to chemotherapy. Responses among 35 assessable patients included 10 partial responses (28.6%). Twenty-one patients had stable disease. The median time to progression was 165 days, and the median overall survival was 310 days. Conclusion The combination of cetuximab, carboplatin, and gemcitabine was well tolerated with an acceptable toxicity profile. Most grade 3 adverse events were attributable to chemotherapy. The response rate and median survival are encouraging and warrant additional investigation.

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