Carlos Camps - Academia.edu (original) (raw)
Papers by Carlos Camps
New England Journal of Medicine
Cancer Medicine, Jul 23, 2021
ObjectivesThe aim of LungBEAM was to determine the value of a novel epidermal growth factor recep... more ObjectivesThe aim of LungBEAM was to determine the value of a novel epidermal growth factor receptor (EGFR) mutation test in blood based on BEAMing technology to predict disease progression in advanced non‐small cell lung cancer (NSCLC) patients treated with first‐ or second‐generation EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs). Another goal was to monitor the dynamics of EGFR mutations, as well as to track EGFR exon 20 p.T790M (p.T790M) resistance during treatment, as critical indicators of therapeutic efficacy and patient survival.MethodsStage IV NSCLC patients with locally confirmed EGFR‐TKI sensitizing mutations (ex19del and/or L858R) in biopsy tissue who were candidates to receive first‐ or second‐generation EGFR‐TKI as first‐line therapy were included. Plasma samples were obtained at baseline and every 4 weeks during treatment until a progression‐free survival (PFS) event or until study completion (72‐week follow‐up). The mutant allele fraction (MAF) was determined for each identified mutation using BEAMing.ResultsA total of 68 of the 110 (61.8%) patients experienced a PFS event. Twenty‐six patients (23.6%) presented with an emergent p.T790M mutation in plasma at some point during follow‐up, preceding radiologic progression with a median of 76 (interquartile ratio: 54–111) days. Disease progression correlated with the appearance of p.T790M in plasma with a hazard ratio (HR) of 1.94 (95% confidence interval [CI], 1.48–2.54; p < 0.001). The HR for progression in patients showing increasing plasma sensitizing mutation levels (positive MAF slope) versus patients showing either decreasing or unchanged plasma mutation levels (negative or null MAF slopes) was 3.85 (95% CI, 2.01–7.36; p < 0.001).ConclusionDetection and quantification of EGFR mutations in circulating tumor DNA using the highly sensitive BEAMing method should greatly assist in optimizing treatment decisions for advanced NSCLC patients.
Oncotarget, Jan 2, 2018
Circulating tumor DNA (ctDNA) levels correlate well with tumor bulk. In this paper we aim to esti... more Circulating tumor DNA (ctDNA) levels correlate well with tumor bulk. In this paper we aim to estimate the prognostic value of the dynamic quantification of ctDNA levels. A total of 251 serial plasma samples from 41 non-small-cell lung cancer patients who carried an activating EGFR mutation were analysed by digital PCR. For survival analysis, ctDNA levels were computed as a time-dependent covariate. Dynamic ctDNA measurements had prognostic significance (hazard ratio for overall survival and progression free survival according to p.T790M mutant allele frequency; 2.676 and 2.71 respectively;< 0.05). In the same way, patients with p.T790M-negative or unchanging or decreasing plasma levels of sensitizing EGFR mutation were 12 and 4.8 times more likely to maintain response or stable disease, respectively, than patients in which the opposite occurred (< 0.05).On average, the p.T790M mutation was detected in plasma 51 days before the assessment of progression disease by CT-scan. Fina...
Clinical Lung Cancer, 2017
Correlation of DNA repair gene polymorphisms with clinical outcome in locally advanced non-small-... more Correlation of DNA repair gene polymorphisms with clinical outcome in locally advanced non-small-cell lung cancer patients receiving induction chemotherapy followed by surgery
Translational lung cancer research, 2013
Metastatic non-small cell lung cancer (NSCLC) unfortunately remains a lethal disease, despite rec... more Metastatic non-small cell lung cancer (NSCLC) unfortunately remains a lethal disease, despite recent genetic characterization of subclasses of NSCLC, mainly adenocarcinoma, which has led to the development of targeted therapies that improve progression-free survival (PFS). Ultimately, however, patients fatally relapse. In this review we will focus on the search to improve survival for NSCLC patients deemed to be pan-negative for the common driver alterations susceptible to targeted therapy, above all those with EGFR mutations or ALK, ROS or RET translocations. Other uncommon driver mutations such as HER2 and BRAF mutations should be tested in order to rule out targeted treatment before assigning patients to chemotherapy. Chemotherapy yields short lived response with median survival still less than one year. Customized chemotherapy represents one way to attempt to prolong survival, although to date no prospective randomized customized studies have reported sufficient evidence to supp...
Clinical cancer research : an official journal of the American Association for Cancer Research, 1998
Paclitaxel and etoposide are two chemotherapy agents with broad cytotoxic activity and different ... more Paclitaxel and etoposide are two chemotherapy agents with broad cytotoxic activity and different mechanisms of action and resistance. Preclinical studies of their combined cytotoxicity have yielded conflicting results. We performed two sequential Phase II trials using different sequence schedules of paclitaxel and etoposide as first-line treatment in advanced non-small cell lung cancer (NSCLC). Forty-four patients with stage IIIB or IV NSCLC were included between July 1995 and September 1996. All patients received etoposide at 100 mg/m2, given as an i.v. infusion on days 1, 2, and 3. The first 20 patients (part A) also received paclitaxel at 175 mg/m2 as a 3-h infusion on day 1, immediately prior to etoposide. The subsequent 24 patients (part B) were given the same paclitaxel dose, but on day 4. Grade 3-4 granulocytopenia was seen in 70% of the patients in part A and in 37% of those in part B (P = 0.04). Twenty-five % of the courses in part A and 4% of the courses in part B were ass...
BMC Urology, 2015
Background: More than 429,000 patients worldwide are diagnosed with bladder cancer each year and ... more Background: More than 429,000 patients worldwide are diagnosed with bladder cancer each year and muscle-invasive bladder cancer has an especially poor outcome. The median age at diagnosis is over 70 years, and many patients also have a substantial number of age-associated impairments that need to be considered when planning therapeutic interventions. Case presentation: Here, we report the case of a 63-year-old man with a cT3b urothelial carcinoma which was surgically removed. No neoadjuvant or adjuvant chemotherapy was administered. After 18 months a lung metastasis was confirmed and resected but no chemotherapy was given after surgery. Twelve months later, the patient relapsed and was treated with a combination of gemcitabine and cisplatin and after a decline in renal function the treatment was changed to a combination of carboplatin and gemcitabine which resulted in a partial response which lasted 8 months. Following this vinflunine was administered as a second line treatment. Here we review the evidence available in the literature regarding the suitability of different treatment options for managing muscle-invasive bladder cancer at each step of the case presentation. Conclusion: Bladder cancer treatment requires a multidisciplinary approach. Although, depending on the clinical characteristics of the patient, there are some controversial points in the management of this pathology we hope that the scientific data and the clinical trials reviewed in this case report, can help to guide physicians to make more rational decisions regarding the management of these patients.
Revue des Maladies Respiratoires, 2006
Future Oncology, 2014
Lung cancer is the leading cause of cancer death worldwide. Therefore, advances in the diagnosis ... more Lung cancer is the leading cause of cancer death worldwide. Therefore, advances in the diagnosis and treatment of the disease are urgently needed. miRNAs are a family of small, noncoding RNAs that regulate gene expression at the transcriptional level. miRNAs have been reported to be deregulated and to play a critical role in different types of cancer, including lung cancer. Thus, miRNA profiling in lung cancer patients has become the core of several investigations. To this end, the development of a multitude of platforms for miRNA profiling analysis has been essential. This article focuses on the different technologies available for assessing miRNAs and the most important results obtained to date in lung cancer.
Clinical cancer research : an official journal of the American Association for Cancer Research, 2002
Overexpression of the excision repair cross-complementing 1 (ERCC1) gene, which is crucial in the... more Overexpression of the excision repair cross-complementing 1 (ERCC1) gene, which is crucial in the repair of cisplatin (CDDP)-DNA adducts, is reported to negatively influence the effectiveness of CDDP-based therapy for gastric and ovarian cancers. Recent evidence indicates that Gemcitabine (Gem) may modulate ERCC1 nucleotide excision repair activity, and down-regulation of DNA repair activity by ERCC1 antisense RNA reportedly inhibits synergism of CDDP/Gem. We investigated whether ERCC1 mRNA expression levels were associated with clinical outcomes after treatment with a combination Gem/CDDP regimen for patients with advanced stage non-small cell lung cancer (NSCLC). Response and survival were correlated with the level of ERCC1 expression in 56 patients with advanced (stage IIIb or IV) NSCLC treated as part of a multicenter randomized trial with Gem 1250 mg/m(2) days 1 and 8 plus CDDP 100 mg/m(2) on day 1 every 3 weeks. mRNA was isolated from paraffin-embedded pretreatment primary tum...
Annals of Oncology, 2014
Background: In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and re... more Background: In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients. Patients and methods: Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial.
New England Journal of Medicine, 2009
Background Activating mutations in the epidermal growth factor receptor gene (EGFR) confer hypers... more Background Activating mutations in the epidermal growth factor receptor gene (EGFR) confer hypersensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in patients with advanced non-small-cell lung cancer. We evaluated the feasibility of large-scale screening for EGFR mutations in such patients and analyzed the association between the mutations and the outcome of erlotinib treatment. Methods From April 2005 through November 2008, lung cancers from 2105 patients in 129 institutions in Spain were screened for EGFR mutations. The analysis was performed in a central laboratory. Patients with tumors carrying EGFR mutations were eligible for erlotinib treatment. Results EGFR mutations were found in 350 of 2105 patients (16.6%). Mutations were more frequent in women (69.7%), in patients who had never smoked (66.6%), and in those with adenocarcinomas (80.9%) (P<0.001 for all comparisons). The mutations were deletions in exon 19 (62.2%) and L858R (37.8%). Median progression-free survival and overall survival for 217 patients who received erlotinib were 14 months and 27 months, respectively. The adjusted hazard ratios for the duration of progressionfree survival were 2.94 for men (P<0.001); 1.92 for the presence of the L858R mutation, as compared with a deletion in exon 19 (P = 0.02); and 1.68 for the presence of the L858R mutation in paired serum DNA, as compared with the absence of the mutation (P = 0.02). The most common adverse events were mild rashes and diarrhea; grade 3 cutaneous toxic effects were recorded in 16 patients (7.4%) and grade 3 diarrhea in 8 patients (3.7%). Conclusions Large-scale screening of patients with lung cancer for EGFR mutations is feasible and can have a role in decisions about treatment.
Lung Cancer, 2013
S11 tumors had a significantly higher miRNA risk-score than subjects with benign nodules or healt... more S11 tumors had a significantly higher miRNA risk-score than subjects with benign nodules or healthy controls (p-value <0.0001). MiRNA signature had an higher sensitivity than CT/PET (63% versus 53%), particularly among subjects with non-solid nodules (64% versus 18%). The combination of CT/PET and miRNA test correctly classified 83% of tumors. MiRNA and CT/PET specificity was 100% and 92%, respectively. We did not found any statistically significant association between the miRNA risk-score and clinical or radiological characteristics both for tumors and benign nodules. Conclusions: MiRNA risk-score had a higher sensitivity than CT/PET in screen-detected lung cancers. A combination of miRNA test and CT/PET should be prospectively evaluated to optimize the workup for suspicious screen-detected nodules and to reduce the false positive cases at surgery.
Journal of Thoracic Oncology, 2007
background. Results: 805 pts received WBRT (N=403) or MGd+WBRT (N=402). Most pts had multiple BM ... more background. Results: 805 pts received WBRT (N=403) or MGd+WBRT (N=402). Most pts had multiple BM (81%), extracranial metastases (47%) and presented with neurologic deficits (84%). Treatment arms were balanced for key prognostic factors. At baseline, 77% of all patients had some degree of neurocognitive deficit with 18% having one test result abnormal, 20% having two, 18% having three, 16% having four and 5% having all five test results abnormal. Memory was the most frequently impaired function (57%). Baseline neurocognitive impairments were balanced across treatment arms. Patients treated with MGd+WBRT were less likely during follow-up to show evidence of neurocognitive progression in memory function (HR=0.80, p=0.047), in executive function (HR=0.74, p=0.028) or in a combined score for all tests, (HR=0.78, p=0.02). Conclusions: Consistent with the delay in time to clinical neurologic progression seen in a previous pooled analysis, treatment with MGd+WBRT decreased progression in each function measured by standardized neurocognitive testing in the pooled dataset from 2 randomized phase III trials.
Journal of Thoracic Oncology, 2011
Background: Circulating DNA is observed at higher concentrations in patients with lung cancer tha... more Background: Circulating DNA is observed at higher concentrations in patients with lung cancer than in controls. Qualitative and quantitative analysis of circulating DNA is a promising noninvasive tool. Our aim was to prospectively study the association between the catalytic subunit of telomerase (human telomerase reverse transcriptase [hTERT]) in plasma and clinical variables and survival in a large-scale non-small cell lung cancer (NSCLC) study. Methods: Four hundred forty-six patients with stages IIIB and IV NSCLC with a median follow-up of 9.7 months (range, 0.5-45) were analyzed. Blood samples were collected before therapy start (cisplatin/docetaxel). Quantification of baseline circulating DNA was determined as the amount of free hTERT in plasma, by using real-time quantitative polymerase chain reaction. Results: Patients with hTERT Յ49.8 ng/ml (median value) had a median time to progression (TTP) of 6.3 months compared with 4.9 for hTERT more than 49.8 ng/ml (p ϭ 0.001). Overall survival (OS) was significantly higher (10.9 versus 9.3 months) at lower hTERT levels (p ϭ 0.012). When calculations were done using hTERT as continuous variable, we did not observe independent significant differences. Thus, there is an apparent discrepancy in p values when hTERT is considered as a continuous versus dichotomized variable. There was a tendency to differentiate median hTERT levels with respect to response rates (complete response ϩ partial response: 33.1 versus stable disease ϩ progressive disease: 50.7 ng/ml, p ϭ 0.12), but other clinical variables such as age, gender, performance status, stage, histology, and number of metastatic locations were not associated with hTERT. In multivariate analysis, hTERT was an independent prognostic variable for both TTP (hazard ratio: 1.44, p Ͻ 0.001) and OS (hazard ratio: 1.33, p ϭ 0.007). Conclusions: In advanced NSCLC, high pretreatment circulating hTERT level is an independent poor prognostic marker for TTP and OS. Circulating DNA is a noninvasive marker, which may help to improve the prognostic profile of these patients.
Journal of Thoracic Oncology, 2007
study the association between the presence of K-ras mutations at codon 12 and several clinical va... more study the association between the presence of K-ras mutations at codon 12 and several clinical variables in advanced NSCLC patients. Methods: We examined 451 NSCLC patients in stage IIIB and IV, treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the plasma using commercial adsorption columns. K-ras mutational status was determined by a method based in allelic discrimination with RT-PCR. Results: Median age was 61 years [35-82] and 84% were males. 99% had performance status 0-1. 84% were in stage IV and 16% in stage IIIB. The histological subtypes were: 32% squamous cell carcinoma, 50% adenocarcinoma, 14% anaplastic large cell, and 4% undifferentiated. 41% of the patients received second line chemotherapy. 1% achieved complete response (CR), 36% partial response (PR), 35% had stable disease (SD) and 28% progressive disease (PD). Here we present the results of the analysis of K-ras mutations in the plasma of 165 samples. 17 patients presented K-ras mutations (10.3%), being codon 12 TGT in 16 patients and GTT in 1 case. Plasmatic mutations were found either in patients presenting squamous cell carcinoma (n=3) and in patients with adenocarcinoma (14). Patients with K-ras mutations in plasma had a median time to progression (TTP) of 2.3 months (m) [0.5-4.6] while for wild type K-ras was 4.1 m [3.3-4.8], (p=0.9). Overall Survival (OS) in K-ras mutated patients was 10.1 m [4.1-15.8] and in wild type K-ras was 9.0 m [6.9-11.1], (p=0.6). Conclusions: In advanced NSCLC, there were no significant differences between patients with K-ras mutations and those with wild-type genotype with respect to baseline characteristics, response rates, TTP, or OS. Data from the rest of the cohort will be presented at the meeting.
Journal of Thoracic Oncology, 2007
study the association between the presence of K-ras mutations at codon 12 and several clinical va... more study the association between the presence of K-ras mutations at codon 12 and several clinical variables in advanced NSCLC patients. Methods: We examined 451 NSCLC patients in stage IIIB and IV, treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the plasma using commercial adsorption columns. K-ras mutational status was determined by a method based in allelic discrimination with RT-PCR. Results: Median age was 61 years [35-82] and 84% were males. 99% had performance status 0-1. 84% were in stage IV and 16% in stage IIIB. The histological subtypes were: 32% squamous cell carcinoma, 50% adenocarcinoma, 14% anaplastic large cell, and 4% undifferentiated. 41% of the patients received second line chemotherapy. 1% achieved complete response (CR), 36% partial response (PR), 35% had stable disease (SD) and 28% progressive disease (PD). Here we present the results of the analysis of K-ras mutations in the plasma of 165 samples. 17 patients presented K-ras mutations (10.3%), being codon 12 TGT in 16 patients and GTT in 1 case. Plasmatic mutations were found either in patients presenting squamous cell carcinoma (n=3) and in patients with adenocarcinoma (14). Patients with K-ras mutations in plasma had a median time to progression (TTP) of 2.3 months (m) [0.5-4.6] while for wild type K-ras was 4.1 m [3.3-4.8], (p=0.9). Overall Survival (OS) in K-ras mutated patients was 10.1 m [4.1-15.8] and in wild type K-ras was 9.0 m [6.9-11.1], (p=0.6). Conclusions: In advanced NSCLC, there were no significant differences between patients with K-ras mutations and those with wild-type genotype with respect to baseline characteristics, response rates, TTP, or OS. Data from the rest of the cohort will be presented at the meeting.
Journal of Thoracic Oncology, 2007
Journal of Thoracic Oncology, 2007
carcinoma patients, one-year survival rate and median survival time were significantly higher in ... more carcinoma patients, one-year survival rate and median survival time were significantly higher in arm A than in arm B (64.7% vs 26.3%, P=0.021) and (12.5 months vs 8.7months, P=0.033) respectively. Nausea/vomiting occurred more frequently in arm A than in arm B(67.74% vs 40.0%, P=0.030). There was no statistically difference between two groups in the other side-effects. Conclusions: The regimen of NP combined with COX-2 inhibitor celecoxib was effective and tolerable as the first-line chemotherapy in advanced NSCLC.In the subgroup of adenocarcinoma, The one-year survival rate and median survival time of those treated with NP combined with celecoxib were significantly higher.
Journal of Clinical Oncology, 2007
Purpose Although current treatment options for metastatic non–small-cell lung cancer (NSCLC) rely... more Purpose Although current treatment options for metastatic non–small-cell lung cancer (NSCLC) rely on cisplatin-based chemotherapy, individualized approaches to therapy may improve response or reduce unnecessary toxicity. Excision repair cross-complementing 1 (ERCC1) has been associated with cisplatin resistance. We hypothesized that assigning cisplatin based on pretreatment ERCC1 mRNA levels would improve response. Patients and Methods From August 2001 to October 2005, 444 stage IV NSCLC patients were enrolled. RNA was isolated from pretreatment biopsies, and quantitative real-time reverse transcriptase PCR assays were performed to determine ERCC1 mRNA expression. Patients were randomly assigned in a 1:2 ratio to either the control or genotypic arm before ERCC1 assessment. Patients in the control arm received docetaxel plus cisplatin. In the genotypic arm, patients with low ERCC1 levels received docetaxel plus cisplatin, and those with high levels received docetaxel plus gemcitabine...
New England Journal of Medicine
Cancer Medicine, Jul 23, 2021
ObjectivesThe aim of LungBEAM was to determine the value of a novel epidermal growth factor recep... more ObjectivesThe aim of LungBEAM was to determine the value of a novel epidermal growth factor receptor (EGFR) mutation test in blood based on BEAMing technology to predict disease progression in advanced non‐small cell lung cancer (NSCLC) patients treated with first‐ or second‐generation EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs). Another goal was to monitor the dynamics of EGFR mutations, as well as to track EGFR exon 20 p.T790M (p.T790M) resistance during treatment, as critical indicators of therapeutic efficacy and patient survival.MethodsStage IV NSCLC patients with locally confirmed EGFR‐TKI sensitizing mutations (ex19del and/or L858R) in biopsy tissue who were candidates to receive first‐ or second‐generation EGFR‐TKI as first‐line therapy were included. Plasma samples were obtained at baseline and every 4 weeks during treatment until a progression‐free survival (PFS) event or until study completion (72‐week follow‐up). The mutant allele fraction (MAF) was determined for each identified mutation using BEAMing.ResultsA total of 68 of the 110 (61.8%) patients experienced a PFS event. Twenty‐six patients (23.6%) presented with an emergent p.T790M mutation in plasma at some point during follow‐up, preceding radiologic progression with a median of 76 (interquartile ratio: 54–111) days. Disease progression correlated with the appearance of p.T790M in plasma with a hazard ratio (HR) of 1.94 (95% confidence interval [CI], 1.48–2.54; p < 0.001). The HR for progression in patients showing increasing plasma sensitizing mutation levels (positive MAF slope) versus patients showing either decreasing or unchanged plasma mutation levels (negative or null MAF slopes) was 3.85 (95% CI, 2.01–7.36; p < 0.001).ConclusionDetection and quantification of EGFR mutations in circulating tumor DNA using the highly sensitive BEAMing method should greatly assist in optimizing treatment decisions for advanced NSCLC patients.
Oncotarget, Jan 2, 2018
Circulating tumor DNA (ctDNA) levels correlate well with tumor bulk. In this paper we aim to esti... more Circulating tumor DNA (ctDNA) levels correlate well with tumor bulk. In this paper we aim to estimate the prognostic value of the dynamic quantification of ctDNA levels. A total of 251 serial plasma samples from 41 non-small-cell lung cancer patients who carried an activating EGFR mutation were analysed by digital PCR. For survival analysis, ctDNA levels were computed as a time-dependent covariate. Dynamic ctDNA measurements had prognostic significance (hazard ratio for overall survival and progression free survival according to p.T790M mutant allele frequency; 2.676 and 2.71 respectively;< 0.05). In the same way, patients with p.T790M-negative or unchanging or decreasing plasma levels of sensitizing EGFR mutation were 12 and 4.8 times more likely to maintain response or stable disease, respectively, than patients in which the opposite occurred (< 0.05).On average, the p.T790M mutation was detected in plasma 51 days before the assessment of progression disease by CT-scan. Fina...
Clinical Lung Cancer, 2017
Correlation of DNA repair gene polymorphisms with clinical outcome in locally advanced non-small-... more Correlation of DNA repair gene polymorphisms with clinical outcome in locally advanced non-small-cell lung cancer patients receiving induction chemotherapy followed by surgery
Translational lung cancer research, 2013
Metastatic non-small cell lung cancer (NSCLC) unfortunately remains a lethal disease, despite rec... more Metastatic non-small cell lung cancer (NSCLC) unfortunately remains a lethal disease, despite recent genetic characterization of subclasses of NSCLC, mainly adenocarcinoma, which has led to the development of targeted therapies that improve progression-free survival (PFS). Ultimately, however, patients fatally relapse. In this review we will focus on the search to improve survival for NSCLC patients deemed to be pan-negative for the common driver alterations susceptible to targeted therapy, above all those with EGFR mutations or ALK, ROS or RET translocations. Other uncommon driver mutations such as HER2 and BRAF mutations should be tested in order to rule out targeted treatment before assigning patients to chemotherapy. Chemotherapy yields short lived response with median survival still less than one year. Customized chemotherapy represents one way to attempt to prolong survival, although to date no prospective randomized customized studies have reported sufficient evidence to supp...
Clinical cancer research : an official journal of the American Association for Cancer Research, 1998
Paclitaxel and etoposide are two chemotherapy agents with broad cytotoxic activity and different ... more Paclitaxel and etoposide are two chemotherapy agents with broad cytotoxic activity and different mechanisms of action and resistance. Preclinical studies of their combined cytotoxicity have yielded conflicting results. We performed two sequential Phase II trials using different sequence schedules of paclitaxel and etoposide as first-line treatment in advanced non-small cell lung cancer (NSCLC). Forty-four patients with stage IIIB or IV NSCLC were included between July 1995 and September 1996. All patients received etoposide at 100 mg/m2, given as an i.v. infusion on days 1, 2, and 3. The first 20 patients (part A) also received paclitaxel at 175 mg/m2 as a 3-h infusion on day 1, immediately prior to etoposide. The subsequent 24 patients (part B) were given the same paclitaxel dose, but on day 4. Grade 3-4 granulocytopenia was seen in 70% of the patients in part A and in 37% of those in part B (P = 0.04). Twenty-five % of the courses in part A and 4% of the courses in part B were ass...
BMC Urology, 2015
Background: More than 429,000 patients worldwide are diagnosed with bladder cancer each year and ... more Background: More than 429,000 patients worldwide are diagnosed with bladder cancer each year and muscle-invasive bladder cancer has an especially poor outcome. The median age at diagnosis is over 70 years, and many patients also have a substantial number of age-associated impairments that need to be considered when planning therapeutic interventions. Case presentation: Here, we report the case of a 63-year-old man with a cT3b urothelial carcinoma which was surgically removed. No neoadjuvant or adjuvant chemotherapy was administered. After 18 months a lung metastasis was confirmed and resected but no chemotherapy was given after surgery. Twelve months later, the patient relapsed and was treated with a combination of gemcitabine and cisplatin and after a decline in renal function the treatment was changed to a combination of carboplatin and gemcitabine which resulted in a partial response which lasted 8 months. Following this vinflunine was administered as a second line treatment. Here we review the evidence available in the literature regarding the suitability of different treatment options for managing muscle-invasive bladder cancer at each step of the case presentation. Conclusion: Bladder cancer treatment requires a multidisciplinary approach. Although, depending on the clinical characteristics of the patient, there are some controversial points in the management of this pathology we hope that the scientific data and the clinical trials reviewed in this case report, can help to guide physicians to make more rational decisions regarding the management of these patients.
Revue des Maladies Respiratoires, 2006
Future Oncology, 2014
Lung cancer is the leading cause of cancer death worldwide. Therefore, advances in the diagnosis ... more Lung cancer is the leading cause of cancer death worldwide. Therefore, advances in the diagnosis and treatment of the disease are urgently needed. miRNAs are a family of small, noncoding RNAs that regulate gene expression at the transcriptional level. miRNAs have been reported to be deregulated and to play a critical role in different types of cancer, including lung cancer. Thus, miRNA profiling in lung cancer patients has become the core of several investigations. To this end, the development of a multitude of platforms for miRNA profiling analysis has been essential. This article focuses on the different technologies available for assessing miRNAs and the most important results obtained to date in lung cancer.
Clinical cancer research : an official journal of the American Association for Cancer Research, 2002
Overexpression of the excision repair cross-complementing 1 (ERCC1) gene, which is crucial in the... more Overexpression of the excision repair cross-complementing 1 (ERCC1) gene, which is crucial in the repair of cisplatin (CDDP)-DNA adducts, is reported to negatively influence the effectiveness of CDDP-based therapy for gastric and ovarian cancers. Recent evidence indicates that Gemcitabine (Gem) may modulate ERCC1 nucleotide excision repair activity, and down-regulation of DNA repair activity by ERCC1 antisense RNA reportedly inhibits synergism of CDDP/Gem. We investigated whether ERCC1 mRNA expression levels were associated with clinical outcomes after treatment with a combination Gem/CDDP regimen for patients with advanced stage non-small cell lung cancer (NSCLC). Response and survival were correlated with the level of ERCC1 expression in 56 patients with advanced (stage IIIb or IV) NSCLC treated as part of a multicenter randomized trial with Gem 1250 mg/m(2) days 1 and 8 plus CDDP 100 mg/m(2) on day 1 every 3 weeks. mRNA was isolated from paraffin-embedded pretreatment primary tum...
Annals of Oncology, 2014
Background: In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and re... more Background: In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients. Patients and methods: Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial.
New England Journal of Medicine, 2009
Background Activating mutations in the epidermal growth factor receptor gene (EGFR) confer hypers... more Background Activating mutations in the epidermal growth factor receptor gene (EGFR) confer hypersensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in patients with advanced non-small-cell lung cancer. We evaluated the feasibility of large-scale screening for EGFR mutations in such patients and analyzed the association between the mutations and the outcome of erlotinib treatment. Methods From April 2005 through November 2008, lung cancers from 2105 patients in 129 institutions in Spain were screened for EGFR mutations. The analysis was performed in a central laboratory. Patients with tumors carrying EGFR mutations were eligible for erlotinib treatment. Results EGFR mutations were found in 350 of 2105 patients (16.6%). Mutations were more frequent in women (69.7%), in patients who had never smoked (66.6%), and in those with adenocarcinomas (80.9%) (P<0.001 for all comparisons). The mutations were deletions in exon 19 (62.2%) and L858R (37.8%). Median progression-free survival and overall survival for 217 patients who received erlotinib were 14 months and 27 months, respectively. The adjusted hazard ratios for the duration of progressionfree survival were 2.94 for men (P<0.001); 1.92 for the presence of the L858R mutation, as compared with a deletion in exon 19 (P = 0.02); and 1.68 for the presence of the L858R mutation in paired serum DNA, as compared with the absence of the mutation (P = 0.02). The most common adverse events were mild rashes and diarrhea; grade 3 cutaneous toxic effects were recorded in 16 patients (7.4%) and grade 3 diarrhea in 8 patients (3.7%). Conclusions Large-scale screening of patients with lung cancer for EGFR mutations is feasible and can have a role in decisions about treatment.
Lung Cancer, 2013
S11 tumors had a significantly higher miRNA risk-score than subjects with benign nodules or healt... more S11 tumors had a significantly higher miRNA risk-score than subjects with benign nodules or healthy controls (p-value <0.0001). MiRNA signature had an higher sensitivity than CT/PET (63% versus 53%), particularly among subjects with non-solid nodules (64% versus 18%). The combination of CT/PET and miRNA test correctly classified 83% of tumors. MiRNA and CT/PET specificity was 100% and 92%, respectively. We did not found any statistically significant association between the miRNA risk-score and clinical or radiological characteristics both for tumors and benign nodules. Conclusions: MiRNA risk-score had a higher sensitivity than CT/PET in screen-detected lung cancers. A combination of miRNA test and CT/PET should be prospectively evaluated to optimize the workup for suspicious screen-detected nodules and to reduce the false positive cases at surgery.
Journal of Thoracic Oncology, 2007
background. Results: 805 pts received WBRT (N=403) or MGd+WBRT (N=402). Most pts had multiple BM ... more background. Results: 805 pts received WBRT (N=403) or MGd+WBRT (N=402). Most pts had multiple BM (81%), extracranial metastases (47%) and presented with neurologic deficits (84%). Treatment arms were balanced for key prognostic factors. At baseline, 77% of all patients had some degree of neurocognitive deficit with 18% having one test result abnormal, 20% having two, 18% having three, 16% having four and 5% having all five test results abnormal. Memory was the most frequently impaired function (57%). Baseline neurocognitive impairments were balanced across treatment arms. Patients treated with MGd+WBRT were less likely during follow-up to show evidence of neurocognitive progression in memory function (HR=0.80, p=0.047), in executive function (HR=0.74, p=0.028) or in a combined score for all tests, (HR=0.78, p=0.02). Conclusions: Consistent with the delay in time to clinical neurologic progression seen in a previous pooled analysis, treatment with MGd+WBRT decreased progression in each function measured by standardized neurocognitive testing in the pooled dataset from 2 randomized phase III trials.
Journal of Thoracic Oncology, 2011
Background: Circulating DNA is observed at higher concentrations in patients with lung cancer tha... more Background: Circulating DNA is observed at higher concentrations in patients with lung cancer than in controls. Qualitative and quantitative analysis of circulating DNA is a promising noninvasive tool. Our aim was to prospectively study the association between the catalytic subunit of telomerase (human telomerase reverse transcriptase [hTERT]) in plasma and clinical variables and survival in a large-scale non-small cell lung cancer (NSCLC) study. Methods: Four hundred forty-six patients with stages IIIB and IV NSCLC with a median follow-up of 9.7 months (range, 0.5-45) were analyzed. Blood samples were collected before therapy start (cisplatin/docetaxel). Quantification of baseline circulating DNA was determined as the amount of free hTERT in plasma, by using real-time quantitative polymerase chain reaction. Results: Patients with hTERT Յ49.8 ng/ml (median value) had a median time to progression (TTP) of 6.3 months compared with 4.9 for hTERT more than 49.8 ng/ml (p ϭ 0.001). Overall survival (OS) was significantly higher (10.9 versus 9.3 months) at lower hTERT levels (p ϭ 0.012). When calculations were done using hTERT as continuous variable, we did not observe independent significant differences. Thus, there is an apparent discrepancy in p values when hTERT is considered as a continuous versus dichotomized variable. There was a tendency to differentiate median hTERT levels with respect to response rates (complete response ϩ partial response: 33.1 versus stable disease ϩ progressive disease: 50.7 ng/ml, p ϭ 0.12), but other clinical variables such as age, gender, performance status, stage, histology, and number of metastatic locations were not associated with hTERT. In multivariate analysis, hTERT was an independent prognostic variable for both TTP (hazard ratio: 1.44, p Ͻ 0.001) and OS (hazard ratio: 1.33, p ϭ 0.007). Conclusions: In advanced NSCLC, high pretreatment circulating hTERT level is an independent poor prognostic marker for TTP and OS. Circulating DNA is a noninvasive marker, which may help to improve the prognostic profile of these patients.
Journal of Thoracic Oncology, 2007
study the association between the presence of K-ras mutations at codon 12 and several clinical va... more study the association between the presence of K-ras mutations at codon 12 and several clinical variables in advanced NSCLC patients. Methods: We examined 451 NSCLC patients in stage IIIB and IV, treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the plasma using commercial adsorption columns. K-ras mutational status was determined by a method based in allelic discrimination with RT-PCR. Results: Median age was 61 years [35-82] and 84% were males. 99% had performance status 0-1. 84% were in stage IV and 16% in stage IIIB. The histological subtypes were: 32% squamous cell carcinoma, 50% adenocarcinoma, 14% anaplastic large cell, and 4% undifferentiated. 41% of the patients received second line chemotherapy. 1% achieved complete response (CR), 36% partial response (PR), 35% had stable disease (SD) and 28% progressive disease (PD). Here we present the results of the analysis of K-ras mutations in the plasma of 165 samples. 17 patients presented K-ras mutations (10.3%), being codon 12 TGT in 16 patients and GTT in 1 case. Plasmatic mutations were found either in patients presenting squamous cell carcinoma (n=3) and in patients with adenocarcinoma (14). Patients with K-ras mutations in plasma had a median time to progression (TTP) of 2.3 months (m) [0.5-4.6] while for wild type K-ras was 4.1 m [3.3-4.8], (p=0.9). Overall Survival (OS) in K-ras mutated patients was 10.1 m [4.1-15.8] and in wild type K-ras was 9.0 m [6.9-11.1], (p=0.6). Conclusions: In advanced NSCLC, there were no significant differences between patients with K-ras mutations and those with wild-type genotype with respect to baseline characteristics, response rates, TTP, or OS. Data from the rest of the cohort will be presented at the meeting.
Journal of Thoracic Oncology, 2007
study the association between the presence of K-ras mutations at codon 12 and several clinical va... more study the association between the presence of K-ras mutations at codon 12 and several clinical variables in advanced NSCLC patients. Methods: We examined 451 NSCLC patients in stage IIIB and IV, treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the plasma using commercial adsorption columns. K-ras mutational status was determined by a method based in allelic discrimination with RT-PCR. Results: Median age was 61 years [35-82] and 84% were males. 99% had performance status 0-1. 84% were in stage IV and 16% in stage IIIB. The histological subtypes were: 32% squamous cell carcinoma, 50% adenocarcinoma, 14% anaplastic large cell, and 4% undifferentiated. 41% of the patients received second line chemotherapy. 1% achieved complete response (CR), 36% partial response (PR), 35% had stable disease (SD) and 28% progressive disease (PD). Here we present the results of the analysis of K-ras mutations in the plasma of 165 samples. 17 patients presented K-ras mutations (10.3%), being codon 12 TGT in 16 patients and GTT in 1 case. Plasmatic mutations were found either in patients presenting squamous cell carcinoma (n=3) and in patients with adenocarcinoma (14). Patients with K-ras mutations in plasma had a median time to progression (TTP) of 2.3 months (m) [0.5-4.6] while for wild type K-ras was 4.1 m [3.3-4.8], (p=0.9). Overall Survival (OS) in K-ras mutated patients was 10.1 m [4.1-15.8] and in wild type K-ras was 9.0 m [6.9-11.1], (p=0.6). Conclusions: In advanced NSCLC, there were no significant differences between patients with K-ras mutations and those with wild-type genotype with respect to baseline characteristics, response rates, TTP, or OS. Data from the rest of the cohort will be presented at the meeting.
Journal of Thoracic Oncology, 2007
Journal of Thoracic Oncology, 2007
carcinoma patients, one-year survival rate and median survival time were significantly higher in ... more carcinoma patients, one-year survival rate and median survival time were significantly higher in arm A than in arm B (64.7% vs 26.3%, P=0.021) and (12.5 months vs 8.7months, P=0.033) respectively. Nausea/vomiting occurred more frequently in arm A than in arm B(67.74% vs 40.0%, P=0.030). There was no statistically difference between two groups in the other side-effects. Conclusions: The regimen of NP combined with COX-2 inhibitor celecoxib was effective and tolerable as the first-line chemotherapy in advanced NSCLC.In the subgroup of adenocarcinoma, The one-year survival rate and median survival time of those treated with NP combined with celecoxib were significantly higher.
Journal of Clinical Oncology, 2007
Purpose Although current treatment options for metastatic non–small-cell lung cancer (NSCLC) rely... more Purpose Although current treatment options for metastatic non–small-cell lung cancer (NSCLC) rely on cisplatin-based chemotherapy, individualized approaches to therapy may improve response or reduce unnecessary toxicity. Excision repair cross-complementing 1 (ERCC1) has been associated with cisplatin resistance. We hypothesized that assigning cisplatin based on pretreatment ERCC1 mRNA levels would improve response. Patients and Methods From August 2001 to October 2005, 444 stage IV NSCLC patients were enrolled. RNA was isolated from pretreatment biopsies, and quantitative real-time reverse transcriptase PCR assays were performed to determine ERCC1 mRNA expression. Patients were randomly assigned in a 1:2 ratio to either the control or genotypic arm before ERCC1 assessment. Patients in the control arm received docetaxel plus cisplatin. In the genotypic arm, patients with low ERCC1 levels received docetaxel plus cisplatin, and those with high levels received docetaxel plus gemcitabine...