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Papers by Lisardo Ugidos

Journal of Clinical Oncology

3612 Background: Despite optimal treatment sequence are still challenging, Neoadjuvant chemothera... more 3612 Background: Despite optimal treatment sequence are still challenging, Neoadjuvant chemotherapy (NAC) followed by chemoradiotherapy (CRT) in patients with local rectal cancer (LRC), known as total neoadjuvant therapy (TNT), offers early treatment of micrometastases, with optimal exposure to systemic chemotherapy (CT) and rapid relief of local symptoms. In one hand, Nal-IRI has demonstrated efficacy and safety in the treatment of GI tumors. On the other hand, Watch and Wait (W&W) protocol is currently being imposed as an alternative to surgery in selected patients with LCR who achieve complete clinical response (cCR), offering the possibility of a rectum preservation strategy without the need to surgical intervention. Accordingly, TNT with NAC Nal-IRI, 5-FU, Oxaliplatin (NALIRINOX) could help to increase cCR rates in LRC treatment, allowing to enter W&W protocol. Methods: We performed a national, single arm, multicenter phase II study of patients with LRC treated with biweekly NA...

The treatment and management of localized rectal cancer has evolved exponentially in recent years... more The treatment and management of localized rectal cancer has evolved exponentially in recent years. Thanks to improvements in neoadjuvant treatments and the possibility of close follow-up programs with organ preservation (watch and wait) in patients who acquire clinical complete response their quality of life has improved substantially. We present a clinical case of rectal cancer in neoadjuvant treatment complicated with tumor perianal fistula, its management and impact on its follow-up.

Oncology, 2021

Introduction: Phase I trials aim to determine the maximum-tolerated dose of a particular drug whi... more Introduction: Phase I trials aim to determine the maximum-tolerated dose of a particular drug while minimizing the number of patients exposed to either sub-therapeutic doses or severe toxicity. Thus, patient selection for phase I trials is a key component of any clinical trial design. Though several studies have been made to address this issue, patient selection still represents a major clinical challenge that needs further investigation. Methods: Twenty-nine baseline clinical and analytical characteristics of 773 consecutive patients treated in phase I trials between 2008 and 2016 in START Madrid-CIOCC were analysed and correlated to objective response (OR), progression-free survival, median overall survival, toxicity, and treatment type. The ones associated to OR in the univariate analysis were included in the stepwise logistic regression multivariate and Cox analysis. The statistically significant ones were included in a predictive score (named here as the Madrid score) of antitu...

Japan Journal of Research, 2020

Investigational New Drugs, 2021

Introduction The number of cancer cases among the elderly continue to increase as the worldwide p... more Introduction The number of cancer cases among the elderly continue to increase as the worldwide population ages. This patient subset is underrepresented in clinical trials, partly because of unresolved uncertainties about age-associated tolerabilities and antitumor activities. We reviewed phase 1 trial data to study tolerance and efficacy of novel agents used for treatment of elderly patients with cancer. Methods Data from 773 consecutive evaluable patients in 85 phase 1 clinical trials (2008–2016) at START Madrid-CIOCC were analyzed according to age, with respect to objective response, survival, and toxicity. Results The mean age was 58.7 (range: 18–87) years; 260 (33.6%) patients were >65 y (elderly group). One hundred thirty-seven (17.8%) patients received immunotherapy drugs, 308 (39.8%) received targeted agents, and 328 (42.4%) received chemotherapy. No statistically significant differences in overall survival, objective response, or severe toxicity rates were found according to treatment type. Similar toxicities and clinical activities were found between the two age subgroups; 18.8% of the elderly and 20.7% of the younger patients experienced severe hematological toxicity (p=0.5), and 30.2% and 32.7%, respectively, experienced severe non-hematological toxicity (p=0.4). Regarding antitumor activity, 12.4% of the elderly and 15% of the younger patients achieved objective responses (p=0.41). There were no significant between-group differences in overall survival (9.7 versus 11.5 months, respectively, p=0.1) or progression-free survival (2.3 versus 2.2 months, respectively, p=0.7). Conclusions This retrospective study found that elderly and younger populations had comparable antitumor activities and toxicity profiles. These results support including elderly patients with cancer in early-phase trials.

Journal of Clinical Oncology, 2009

11074 Background: Treatment options for patients (pts) with colorectal cancer (CRC) have increase... more 11074 Background: Treatment options for patients (pts) with colorectal cancer (CRC) have increased in the last years. However, there are no validated prospective molecular markers in CRC to select which agents are better to treat any individual case. The aim of this study was to determine the feasibility of developing an implementing a biomarker panel to guide treatment selection in this setting. Methods: Colorectal cancer tumors were prospectively analyzed with a predefined set of 11 molecular targets, including: KRas and PI3K mutations, EGFR amplification (FISH), and ERCC-1, TS, TP expression by IHC. Clinical characteristics and response to chemotherapy were registered. To establish the utility of this panel, we determine as congruent-treatment if the panel predict the best treatment in patients with more of 1 chemotherapy line and no-congruent-treatment if do not. Results: A total of 84 patients were studied. Only 6 % required a repeated biopsy to obtain sufficient tumor for mark...

Journal of Clinical Oncology, 2017

e18202 Background: The faculty clinical activity in a comprehensive Cancer Center is difficult to... more e18202 Background: The faculty clinical activity in a comprehensive Cancer Center is difficult to measure. Time clinical units is the most common procedure worldwide. In our group we have developed a new system based on the daily real activity of each medical oncologist of our team. Methods: We collected the daily activity from january to december 2016 of each doctor considering different values( from 1 to 4)depending on the complexity of the activity. Follow up visit of a patient (1), treatment visit (2). Clinical trial visit or Inpatient visit (3) and New Patient First visit (4). Then we added all the daily values of each medical oncologist. Results: 2016 Clinical activity growth measured by traditional time methods was consider 31,5%. When we applicated our new method it was 33,4%. The clinical activity of each Oncology Unit changed clearly when we applied our method. For example , breast cancer unit change from 25% to 20 % of the global activity, GI Unit from 47% to 50%, Lung Un...

Journal of Clinical Oncology, 2017

e14029 Background: A usual inclusion criterion for phase I trials is life expectancy of more than... more e14029 Background: A usual inclusion criterion for phase I trials is life expectancy of more than 3 months. Prediction of early mortality (EM), in the first 90 days after starting treatment, is thus a challenge. Predictive scores may help to select more adequate patients (pts). Our main objective was to generate a predictive score in a training set of phase I pts and to confirm it in a validation score. Secondly, we figured out if our score also predicts overall survival (OS). Methods: Consecutive pts treated in our phase I unit between 2008 and 2013 were retrospectively reviewed. We collected 35 clinical and analytical characteristics at base line. Stepwise regression was used to correlate pts characteristics with EM and generate a predictive score. Log-rank regression and Kaplan Meier curves were used to study survival. Results: We identified 438 pts. Median age was 61 yr (18-87) and 52.7% were male. More frequent tumor types were gastrointestinal (37%), thoracic (17%), and breast...

Journal of Clinical Oncology, 2016

e23059Background: RAS/RAF/PIK3CA mutations are frequent drivers of secondary drug resistance to c... more e23059Background: RAS/RAF/PIK3CA mutations are frequent drivers of secondary drug resistance to cetuximab in mCCR, which typically occurs within 3-12months from the start of therapy. The emergence ...

Journal of Clinical Oncology, 2016

4109Background: nab-paclitaxel + gemcitabine is approved for the treatment of metastastic pancrea... more 4109Background: nab-paclitaxel + gemcitabine is approved for the treatment of metastastic pancreatic cancer. So far, few studies have investigate this regimen in patients with nonmetastatic disease...

Annals of Oncology, 2019

Background Preliminary studies have suggested that the activity of anti-PD-1 immune check-point i... more Background Preliminary studies have suggested that the activity of anti-PD-1 immune check-point inhibitors in thyroid cancer is low. However, we hypothesize that combining CTLA-4 and PD-L1 clockade could have a higher effet in the setting of refractory thyroid carcinomas, in which the process of de-differentiation and evasive tumor resistance are associated with increased mutational load. Trial design This prospective, multi-center, open-label, phase II study will evaluate the efficacy and safety of Durvalumab plus Tremelimumab within three parallel cohorts: differentiated (DTC), medullary (MTC), and anaplastic (ATC) thyroid cancers. Pts will receive Durvalumab 1500mg plus Tremelimumab 75mg every 4 weeks for up to 4 cycles followed by Durvalumab until PD, unacceptable toxicity or patients’ decision. Main end point in cohorts 1 and 2 is progression-free survival (PFS). We hypothesize an increase of 6-months from 25% in historical cohorts up to 45%. A Simon two-stage design will be em...

Journal of Clinical Oncology, 2016

e15714Background: Excission Repair Cross-Complementing 1 (ERCC-1) has been shown to increase the ... more e15714Background: Excission Repair Cross-Complementing 1 (ERCC-1) has been shown to increase the resistance to platinum in some cancers. ERCC-1 expression was investigated as a predictor of respons...

Journal of Cancer Treatment and Research, 2019

Journal of Clinical Oncology

3612 Background: Despite optimal treatment sequence are still challenging, Neoadjuvant chemothera... more 3612 Background: Despite optimal treatment sequence are still challenging, Neoadjuvant chemotherapy (NAC) followed by chemoradiotherapy (CRT) in patients with local rectal cancer (LRC), known as total neoadjuvant therapy (TNT), offers early treatment of micrometastases, with optimal exposure to systemic chemotherapy (CT) and rapid relief of local symptoms. In one hand, Nal-IRI has demonstrated efficacy and safety in the treatment of GI tumors. On the other hand, Watch and Wait (W&W) protocol is currently being imposed as an alternative to surgery in selected patients with LCR who achieve complete clinical response (cCR), offering the possibility of a rectum preservation strategy without the need to surgical intervention. Accordingly, TNT with NAC Nal-IRI, 5-FU, Oxaliplatin (NALIRINOX) could help to increase cCR rates in LRC treatment, allowing to enter W&W protocol. Methods: We performed a national, single arm, multicenter phase II study of patients with LRC treated with biweekly NA...

The treatment and management of localized rectal cancer has evolved exponentially in recent years... more The treatment and management of localized rectal cancer has evolved exponentially in recent years. Thanks to improvements in neoadjuvant treatments and the possibility of close follow-up programs with organ preservation (watch and wait) in patients who acquire clinical complete response their quality of life has improved substantially. We present a clinical case of rectal cancer in neoadjuvant treatment complicated with tumor perianal fistula, its management and impact on its follow-up.

Oncology, 2021

Introduction: Phase I trials aim to determine the maximum-tolerated dose of a particular drug whi... more Introduction: Phase I trials aim to determine the maximum-tolerated dose of a particular drug while minimizing the number of patients exposed to either sub-therapeutic doses or severe toxicity. Thus, patient selection for phase I trials is a key component of any clinical trial design. Though several studies have been made to address this issue, patient selection still represents a major clinical challenge that needs further investigation. Methods: Twenty-nine baseline clinical and analytical characteristics of 773 consecutive patients treated in phase I trials between 2008 and 2016 in START Madrid-CIOCC were analysed and correlated to objective response (OR), progression-free survival, median overall survival, toxicity, and treatment type. The ones associated to OR in the univariate analysis were included in the stepwise logistic regression multivariate and Cox analysis. The statistically significant ones were included in a predictive score (named here as the Madrid score) of antitu...

Japan Journal of Research, 2020

Investigational New Drugs, 2021

Introduction The number of cancer cases among the elderly continue to increase as the worldwide p... more Introduction The number of cancer cases among the elderly continue to increase as the worldwide population ages. This patient subset is underrepresented in clinical trials, partly because of unresolved uncertainties about age-associated tolerabilities and antitumor activities. We reviewed phase 1 trial data to study tolerance and efficacy of novel agents used for treatment of elderly patients with cancer. Methods Data from 773 consecutive evaluable patients in 85 phase 1 clinical trials (2008–2016) at START Madrid-CIOCC were analyzed according to age, with respect to objective response, survival, and toxicity. Results The mean age was 58.7 (range: 18–87) years; 260 (33.6%) patients were >65 y (elderly group). One hundred thirty-seven (17.8%) patients received immunotherapy drugs, 308 (39.8%) received targeted agents, and 328 (42.4%) received chemotherapy. No statistically significant differences in overall survival, objective response, or severe toxicity rates were found according to treatment type. Similar toxicities and clinical activities were found between the two age subgroups; 18.8% of the elderly and 20.7% of the younger patients experienced severe hematological toxicity (p=0.5), and 30.2% and 32.7%, respectively, experienced severe non-hematological toxicity (p=0.4). Regarding antitumor activity, 12.4% of the elderly and 15% of the younger patients achieved objective responses (p=0.41). There were no significant between-group differences in overall survival (9.7 versus 11.5 months, respectively, p=0.1) or progression-free survival (2.3 versus 2.2 months, respectively, p=0.7). Conclusions This retrospective study found that elderly and younger populations had comparable antitumor activities and toxicity profiles. These results support including elderly patients with cancer in early-phase trials.

Journal of Clinical Oncology, 2009

11074 Background: Treatment options for patients (pts) with colorectal cancer (CRC) have increase... more 11074 Background: Treatment options for patients (pts) with colorectal cancer (CRC) have increased in the last years. However, there are no validated prospective molecular markers in CRC to select which agents are better to treat any individual case. The aim of this study was to determine the feasibility of developing an implementing a biomarker panel to guide treatment selection in this setting. Methods: Colorectal cancer tumors were prospectively analyzed with a predefined set of 11 molecular targets, including: KRas and PI3K mutations, EGFR amplification (FISH), and ERCC-1, TS, TP expression by IHC. Clinical characteristics and response to chemotherapy were registered. To establish the utility of this panel, we determine as congruent-treatment if the panel predict the best treatment in patients with more of 1 chemotherapy line and no-congruent-treatment if do not. Results: A total of 84 patients were studied. Only 6 % required a repeated biopsy to obtain sufficient tumor for mark...

Journal of Clinical Oncology, 2017

e18202 Background: The faculty clinical activity in a comprehensive Cancer Center is difficult to... more e18202 Background: The faculty clinical activity in a comprehensive Cancer Center is difficult to measure. Time clinical units is the most common procedure worldwide. In our group we have developed a new system based on the daily real activity of each medical oncologist of our team. Methods: We collected the daily activity from january to december 2016 of each doctor considering different values( from 1 to 4)depending on the complexity of the activity. Follow up visit of a patient (1), treatment visit (2). Clinical trial visit or Inpatient visit (3) and New Patient First visit (4). Then we added all the daily values of each medical oncologist. Results: 2016 Clinical activity growth measured by traditional time methods was consider 31,5%. When we applicated our new method it was 33,4%. The clinical activity of each Oncology Unit changed clearly when we applied our method. For example , breast cancer unit change from 25% to 20 % of the global activity, GI Unit from 47% to 50%, Lung Un...

Journal of Clinical Oncology, 2017

e14029 Background: A usual inclusion criterion for phase I trials is life expectancy of more than... more e14029 Background: A usual inclusion criterion for phase I trials is life expectancy of more than 3 months. Prediction of early mortality (EM), in the first 90 days after starting treatment, is thus a challenge. Predictive scores may help to select more adequate patients (pts). Our main objective was to generate a predictive score in a training set of phase I pts and to confirm it in a validation score. Secondly, we figured out if our score also predicts overall survival (OS). Methods: Consecutive pts treated in our phase I unit between 2008 and 2013 were retrospectively reviewed. We collected 35 clinical and analytical characteristics at base line. Stepwise regression was used to correlate pts characteristics with EM and generate a predictive score. Log-rank regression and Kaplan Meier curves were used to study survival. Results: We identified 438 pts. Median age was 61 yr (18-87) and 52.7% were male. More frequent tumor types were gastrointestinal (37%), thoracic (17%), and breast...

Journal of Clinical Oncology, 2016

e23059Background: RAS/RAF/PIK3CA mutations are frequent drivers of secondary drug resistance to c... more e23059Background: RAS/RAF/PIK3CA mutations are frequent drivers of secondary drug resistance to cetuximab in mCCR, which typically occurs within 3-12months from the start of therapy. The emergence ...

Journal of Clinical Oncology, 2016

4109Background: nab-paclitaxel + gemcitabine is approved for the treatment of metastastic pancrea... more 4109Background: nab-paclitaxel + gemcitabine is approved for the treatment of metastastic pancreatic cancer. So far, few studies have investigate this regimen in patients with nonmetastatic disease...

Annals of Oncology, 2019

Background Preliminary studies have suggested that the activity of anti-PD-1 immune check-point i... more Background Preliminary studies have suggested that the activity of anti-PD-1 immune check-point inhibitors in thyroid cancer is low. However, we hypothesize that combining CTLA-4 and PD-L1 clockade could have a higher effet in the setting of refractory thyroid carcinomas, in which the process of de-differentiation and evasive tumor resistance are associated with increased mutational load. Trial design This prospective, multi-center, open-label, phase II study will evaluate the efficacy and safety of Durvalumab plus Tremelimumab within three parallel cohorts: differentiated (DTC), medullary (MTC), and anaplastic (ATC) thyroid cancers. Pts will receive Durvalumab 1500mg plus Tremelimumab 75mg every 4 weeks for up to 4 cycles followed by Durvalumab until PD, unacceptable toxicity or patients’ decision. Main end point in cohorts 1 and 2 is progression-free survival (PFS). We hypothesize an increase of 6-months from 25% in historical cohorts up to 45%. A Simon two-stage design will be em...

Journal of Clinical Oncology, 2016

e15714Background: Excission Repair Cross-Complementing 1 (ERCC-1) has been shown to increase the ... more e15714Background: Excission Repair Cross-Complementing 1 (ERCC-1) has been shown to increase the resistance to platinum in some cancers. ERCC-1 expression was investigated as a predictor of respons...

Journal of Cancer Treatment and Research, 2019