Foundation for Clinical and Applied Cancer Research FICMAC

Bogotá, Colombia

Foundation for Clinical and Applied Cancer Research FICMAC

Bogotá, Colombia
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Cardona A.F.,Institute of Oncology | Cardona A.F.,Foundation for Clinical and Applied Cancer Research FICMAC | Cardona A.F.,El Bosque University | Arrieta O.,Instituto Nacional Of Cancerologia Incan | And 18 more authors.
Targeted Oncology | Year: 2017

Background: Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations. Objective: The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression. Patients and Methods: EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015. Post-progression tumor specimens were collected for molecular analysis. Post-progression interventions, response to treatment, and survival were assessed and compared among all patients and those with and without T790M mutations. Results: Mean age was 59.4 ± 13.9 years, 65% were never-smokers, and 53% had a performance status 0–1. All patients received erlotinib as first-line treatment. Identified mutations included: 60% DelE19 (Del746–750) and 40% L858R. First-line erlotinib overall response rate (ORR) was 61.8% and progression free survival (PFS) was 16.8 months (95% CI: 13.7–19.9). Acquired resistance mutations identified were T790M mutation (47.1%); PI3K mutations (14.7%); EGFR amplification (14.7%); KRAS mutation (5.9%); MET amplification (8.8%); HER2 alterations (5.9%, deletions/insertions in e20); and SCLC transformation (2.9%). Of patients, 79.4% received treatment after progression. ORR for post-erlotinib treatment was 47.1% (CR 2/PR 14) and median PFS was 8.3 months (95% CI: 2.2–36.6). Median overall survival (OS) from treatment initiation was 32.9 months (95% CI: 30.4–35.3), and only the use of post-progression therapy affected OS in a multivariate analysis (p = 0.05). Conclusions: Hispanic patients with acquired resistance to erlotinib continued to be sensitive to other treatments after progression. The proportion of T790M+ patients appears to be similar to that previously reported in Caucasians.[Figure not available: see fulltext.] © 2017 Springer International Publishing Switzerland


Oscar A.,Instituto Nacional Of Cancerologia | Zatarain-Barron Z.L.,Instituto Nacional Of Cancerologia | Andres Felipe C.,Clinical and Traslational Oncology Group | Andres Felipe C.,Foundation for Clinical and Applied Cancer Research FICMAC | And 2 more authors.
Expert Opinion on Drug Safety | Year: 2017

Introduction: Therapeutic options for treating Non-Small Cell Lung Cancer (NSCLC) have recently increased. Ramucirumab (Cyramza), an anti-angionenic agent was approved in 2014 for treatment of several malignancies, including second-line treatment of patients with NSCLC with disease progression on or after platinum-based chemotherapy. Areas covered: We performed a comprehensive search of the literature focused on clinical trials with use of ramucirumab, targeting its evolution in the treatment of NSCLC. This review summarizes the results regarding its safety and efficacy. Expert opinion: Angiogenesis has been widely recognized as a quintessential feature in cancer, intrinsically mediating tumor survival and progression. Ramucirumab, an anti-VEGFR2 agent, combined with docetaxel, was FDA-approved for NSCLC patients. Results from a phase III trial have demonstrated the usefulness of this combination, with benefits in progression free survival and overall survival for NSCLC patients. A greater magnitude of benefit is seen in patients with aggressive tumor behavior. Treatment with ramucirumab is generally tolerable, however, there is potential for severe toxicity. Adverse events reported with this combination include neutropenia, febrile neutropenia and hypertension. Also, there is the intrinsic risk of bleeding resulting from the mechanism of action. As such, adverse events should be identified timely, so drug-related complications can be prevented. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Rojas-Puentes L.,Hospital Universitario San Ignacio | Cardona A.F.,Institute of Oncology | Cardona A.F.,Foundation for Clinical and Applied Cancer Research FICMAC | Carranza H.,Institute of Oncology | And 9 more authors.
Cancer Medicine | Year: 2016

We evaluated the association between epithelial–mesenchymal transition (EMT)-derived markers and expression of proteins associated with cell proliferation and tumor growth, as well as their prognostic roles, in 61 patients (mean age 52 ± 10 years) with locally advanced cervical cancer, all of whom were treated with chemoradiation and intracavitary brachytherapy. We used immunohistochemical analysis to assess the expression of proteins targeted in our investigation. Various statistical analyses were then conducted to assess protein marker associations with survival outcomes. Forty-six percent of the patients were positive for human papilloma virus. Median progression-free survival (PFS) was 6.6 months (95% confidence interval [CI]: 4.0–9.1, whereas overall survival (OS) was 30.0 months (95% CI: 11–48). Multivariate analysis demonstrated that vascular endothelial growth factor (VEGF) (P = 0.002), epidermal growth factor receptor (EGFR) (P = 0.001), and TWIST2 (P = 0.001) expression levels, as well as a tumor size <6 cm (P = 0.02), influenced OS. Changes in TWIST2 levels and loss of E-cadherin expression were correlated with VEGF and EGFR levels; furthermore, patients with high TWIST2 expression had shorter OS (P = 0.0001), as those with loss of E-cadherin (P = 0.02). OS was even shorter when positive EGFR or VEGF expression was related with EMT markers (positive EGFR + negative E-cadherin: median 14 months, 95% CI: 3–24; negative EGFR + positive E-cadherin: median 31 months, 95% CI: 14–NA; P = 0.02.). The presence of EMT markers was associated with proliferative and pro-angiogenic protein expression and influenced the prognosis of locally advanced cervical cancer. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.


Cardona A.F.,Institute of Oncology | Cardona A.F.,Foundation for Clinical and Applied Cancer Research FICMAC | Rojas L.,Foundation for Clinical and Applied Cancer Research FICMAC | Rojas L.,Hospital Universitario San Ignacio | And 15 more authors.
PLoS ONE | Year: 2016

Objective: To evaluate the efficacy and safety of pemetrexed, carboplatin and bevacizumab (PCB) followed by maintenance therapy with pemetrexed and bevacizumab (PB) in chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer (NSCLC) through the influence of thymidylate synthase (TS) protein and mRNA expression on several outcomes. The primary endpoints were the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Methods: A cohort of 144 patients were administered pemetrexed (500 mg/m2), carboplatin (AUC, 5.0 mg/ml/min) and bevacizumab (7.5 mg/kg) intravenously every three weeks for up to four cycles. Maintenance PB was administered until disease progression or unacceptable toxicity. Results: One hundred forty-four Colombian patients with a median follow-up of 13.8 months and a median number of 6 maintenance cycles (range, 1-32) were assessed. The ORR among the patients was 66% (95% CI, 47% to 79%). The median PFS and (OS) rates were 7.9 months (95% CI, 5.9-10.0 months) and 21.4 months (95% CI, 18.3 to 24.4 months), respectively. We documented grade 3/4 hematologic toxicities, including anemia (14%), neutropenia (8%), and thrombocytopenia (16%). The identified grade 3/4 non-hematologic toxicities were proteinuria (2%), venous thrombosis (4%), fatigue (11%), infection (6%), nephrotoxicity (2%), and sensory neuropathy (4%). No grade >3 hemorrhagic events or hypertension cases were reported. OS was significantly higher in patients with the lowest TS mRNA levels [median, 29.6 months (95% CI, 26.2-32.9)] compared with those in patients with higher levels [median, 9.3 months (95% CI, 6.6-12.0); p = 0.0001]. TS expression (mRNA levels or protein expression) did not influence the treatment response. Conclusion: Overall, PCB followed by maintenance pemetrexed and bevacizumab was effective and tolerable in Hispanic patients with non-squamous NSCLC. This regimen was associated with acceptable toxicity and prolonged OS, particularly in patients with low TS expression. We found a role for Ki67 and TS expression as prognostic factors. © 2016 Cardona et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


PubMed | Institute of Oncology, Hospital Of Clinicas Udelar, Alexander Fleming Institute, Hospital San Juan Of Dios and 3 more.
Type: Journal Article | Journal: PloS one | Year: 2016

To evaluate the efficacy and safety of pemetrexed, carboplatin and bevacizumab (PCB) followed by maintenance therapy with pemetrexed and bevacizumab (PB) in chemotherapy-nave patients with stage IV non-squamous non-small cell lung cancer (NSCLC) through the influence of thymidylate synthase (TS) protein and mRNA expression on several outcomes. The primary endpoints were the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).A cohort of 144 patients were administered pemetrexed (500 mg/m2), carboplatin (AUC, 5.0 mg/ml/min) and bevacizumab (7.5 mg/kg) intravenously every three weeks for up to four cycles. Maintenance PB was administered until disease progression or unacceptable toxicity.One hundred forty-four Colombian patients with a median follow-up of 13.8 months and a median number of 6 maintenance cycles (range, 1-32) were assessed. The ORR among the patients was 66% (95% CI, 47% to 79%). The median PFS and (OS) rates were 7.9 months (95% CI, 5.9-10.0 months) and 21.4 months (95% CI, 18.3 to 24.4 months), respectively. We documented grade 3/4 hematologic toxicities, including anemia (14%), neutropenia (8%), and thrombocytopenia (16%). The identified grade 3/4 non-hematologic toxicities were proteinuria (2%), venous thrombosis (4%), fatigue (11%), infection (6%), nephrotoxicity (2%), and sensory neuropathy (4%). No grade >3 hemorrhagic events or hypertension cases were reported. OS was significantly higher in patients with the lowest TS mRNA levels [median, 29.6 months (95% CI, 26.2-32.9)] compared with those in patients with higher levels [median, 9.3 months (95% CI, 6.6-12.0); p = 0.0001]. TS expression (mRNA levels or protein expression) did not influence the treatment response.Overall, PCB followed by maintenance pemetrexed and bevacizumab was effective and tolerable in Hispanic patients with non-squamous NSCLC. This regimen was associated with acceptable toxicity and prolonged OS, particularly in patients with low TS expression. We found a role for Ki67 and TS expression as prognostic factors.


Arrieta O.,National Cancer Institute INCan | Cardona A.F.,Santa Fe Institute | Cardona A.F.,Foundation for Clinical and Applied Cancer Research FICMAC | Corrales L.,Hospital San Juan Of Dios Ccss | And 13 more authors.
Lung Cancer | Year: 2015

Objectives: In non-small cell lung cancer (NSCLC), the association between common EGFR mutations (Del EX19/L858R) with EGFR tyrosine kinase inhibitors (EGFR-TKIs) has been well established. However, this has not been investigated for rare EGFR mutations or their impact on treatment response and outcome to EGFR TKIs (primary objective) and chemotherapy (secondary objective). Materials and methods: In an observational prospective cohort, we analyzed 188 NSCLC patients from Mexico, Colombia and Costa Rica with EGFR mutations. As a first line of treatment, 66.5% received platinum-based chemotherapy. All patients received TKIs in first-line treatment or after progression to chemotherapy. The clinical-pathological characteristics as well as the f of common and rare EGFR mutations associated with treatment response were analyzed. Results: Of all patients, 79.5% had common and 20.5% had rare EGFR mutations. Lepidic and acinar adenocarcinomas were associated with common EGFR mutations (p=. 0.010). Patients with common EGFR mutations had higher response rates to EGFR-TKIs than those who had rare EGFR mutations (63.8 vs 32.4%, p<. 0.001). Women had increased progression-free survival (PFS) to EGFR-TKIs than men (16.4 vs 9.5 months, p=. 0.02). The median PFS and overall survival (OS) were better in patients with common EGFR mutations (15.5 vs 3.9 months, p<. 0.001; and 37.3 vs 17.4 months, p<. 0.001) respectively. Conclusion: Our findings suggested that only patients with rare EGFR mutations could receive platinum-based chemotherapy as a first-line treatment, due to their low response rates and short PFS in response to EGFR-TKIs. Consequently, EGFR-TKIs could be reserved as a second- or third-line treatment. In patients with EGFR mutations, women have better PFS to EGFR-TKIs than men, and rare EGFR mutations are more frequent in high grade adenocarcinomas than in low grade tumors. © 2014 Elsevier Ireland Ltd.


Arrieta O.,Instituto Nacional Of Cancerologia Incan | Varela-Santoyo E.,Instituto Nacional Of Cancerologia Incan | Soto-Perez-de-Celis E.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran | Sanchez-Reyes R.,Instituto Nacional Of Cancerologia Incan | And 4 more authors.
BMC Cancer | Year: 2016

Background: Previous population-based studies have demonstrated an association between metformin use and improved survival among diabetic patients with cancer. We sought to analyze the effects of diabetes and its treatment in terms of the survival of patients with lung cancer. Methods: Overall, 1106 patients with non-small cell lung cancer (94.3 % with stage IV disease) were included. The outcomes were compared between the patients with (n = 186) and without diabetes (n = 920). The characteristics associated with antidiabetic treatment and proper glycemic control (defined as a mean plasma glucose <130 mg/dL) were examined at diagnosis. The overall survivals (OSs) of the different patient populations were analyzed using Kaplan-Meier curves, and a multivariate Cox proportional hazard model was used to determine the influences of the patient and tumor characteristics on survival. Results: The OS for the entire population was 18.3 months (95 % CI 16.1-20.4). There was no difference in the OSs of the diabetic and non-diabetic patients (18.5 vs 16.4 months, p = 0.62). The diabetic patients taking metformin exhibited a superior OS than did those on other antidiabetic treatments (25.6 vs 13.2 months, p = 0.017). Those with proper glycemic control had a better OS than did those without proper glycemic control and the non-diabetics (40.5 vs 13.2 and 18.5 months, respectively, p < 0.001). Both the use of metformin (HR 0.53, p < 0.0001 and HR 0.57, p = 0.017, respectively) and proper glycemic control (HR 0.49, p < 0.0001 and HR 0.40, p = 0.002, respectively) were significant protective factors in all and only diabetic patients, respectively. Conclusions: The diabetic patients with proper glycemic control exhibited a better OS than did those without proper glycemic control and even exhibited a better OS than did the patients without diabetes mellitus. Metformin use was independently associated with a better OS. © 2016 The Author(s).

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