Discoidin domain receptor 2 (DDR2) is arising as a promising therapeutic target in breast carcino... more Discoidin domain receptor 2 (DDR2) is arising as a promising therapeutic target in breast carcinoma (BC). The ability of DDR2 to bind to collagen promotes protumoral responses in cancer cells that influence the tumor microenvironment (TME). Nonetheless, the interrelation between DDR2 expression and TME modulation during BC progression remains poorly known. For this reason, we aim to evaluate the correlation between intratumoral expression of DDR2 and the infiltration of the main TME cell populations, cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs). First, collagen and DDR2 expression levels were analyzed in human invasive BC samples. Then, DDR2 status correlation with tumor aggressiveness and patient survival were retrieved from different databases. Subsequently, the main pathways, cell types, and tissues correlated with DDR2 expression in BC were obtained through bioinformatics approach. Finally, we studied the association of DDR2 expression with the r...
13509 Background: AC is indicated for stage III and high risk stage II colon cancer, as well as f... more 13509 Background: AC is indicated for stage III and high risk stage II colon cancer, as well as for stages II-III rectal cancers combined with RT. Moreover, chemotherapy improves survival in metastatic disease. There are no randomised trials evaluating the role of systemic AC after resection of metastases from CRC. Methods: We retrospectively reviewed patients with completely (R0) removed HM and/or PM from CRC, analysing prognostic factors for overall survival, including AC. Kaplan-Meier method with log rank test was used to assess and compare survival curves. Cox regression model was applied for multivariate analysis. Results: From Jan 1993 to Jun 2004, 146 patients were identified: 98 (67%) with HM, 39 with PM (27%) and 9 (6%) with both HM and PM. Gender (M/F): 102/44. Median age: 65.5 y-o (39.3–82.6). Primary CRC: rectum 62 (42.5%), pN+ 87 (60%), stage IV at diagnosis 57 (39%). Number of metastatic nodules resected: mean 2.25 (1–10). Size of the largest metastasis: mean 4 cm (0.5...
15516 Background: Concomitant CRT has become a standard treatment for advanced head and neck canc... more 15516 Background: Concomitant CRT has become a standard treatment for advanced head and neck cancer. The aim of this study was to evaluate the efficacy and toxicity of concurrent CRT with D in patients (pts) with advanced squamous cell carcinoma of head and neck (SCCHN). Methods: Patients with untreated and unresectable stage III or IV (M0) squamous cell carcinoma of head and neck were included. Treatment consisted of D 20 mg/m2 weekly with concomitant radiotherapy 70 Gy (2 Gy per day, 7 weeks). Results: From September 03 to October 05, sixty-four pts with advanced SCCHN, were recruited. Gender: 61 male, 3 female. Mean age: 56.5 years old (range 42–77). ECOG PS 0/1/2: 0/57/7. Primary sites of disease: oral cavity 8, oropharynx 26, hypopharynx 15 and larynx 15. Stage III 16 pts and stage IV 48 pts. Compliance: 393 administrations of D were given, median 6, mean 6 (range 1–8). Fifty-five pts (86%) completed the radiotherapy dose planned (mean dose of RT was 66 Gy). One refused more tr...
17093 Background: Firstly, we conducted a phase I of a biweekly schedule of cisplatin with prolon... more 17093 Background: Firstly, we conducted a phase I of a biweekly schedule of cisplatin with prolonged infusion of gemcitabine (10 mg/m2/min) and stablished the dose to perform a phase II. We present final results of a phase II with this combination. Methods: Patients with cytologically or histologically confirmed NSCLC stage IIIB and IV were included. Treatment consisted of Cisplatin 50 mg/m2 days 1 and 15 with Gemcitabine 1600 mg/m2 in 160 minutes (10 mg/m2/min), days 1 and 15 every 28 days. Chemotherapy was administered to a maximum of 6 cycles; if radiotherapy was planned, patients received 4 cycles. Results: From March-04 to January-05, 55 patients were included. Patient characteristics: Median age 59 years (35–75). Gender: 51 male 4 female. ECOG performance status 0/1/2: 8/43/4. Histology: Squamous cell carcinoma 26 (47.3%), adenocarcinoma 22 (40%), large cell carcinoma 2 (3.6%), undifferentiated 5 (9%). Stage: IIIA 2 (3.6%), IIIB 27 (49.1%) and IV 26 (47.3%). Treatment complian...
Aims and Background The objective of the study was to evaluate the efficacy of combined chemoradi... more Aims and Background The objective of the study was to evaluate the efficacy of combined chemoradiation in patients with newly diagnosed glioblastoma multiforme. The main end points were time to progression and overall survival. Methods Thirty-one patients with glioblastoma multiforme underwent surgery whenever possible and then received intravenous VM26 (120 mg/m2) and oral CCNU (120 mg/m2) for three cycles followed by radiotherapy (60 Gy). Results Surgery consisted of a complete resection in 39% of patients, partial resection in 35% and a biopsy in 26%. Sixteen patients had clinical or radiological evidence of progression during or after chemotherapy. Hematologic toxicity was mild. Forty-five percent of patients received the scheduled dose of radiation. The outcome was disappointing, with a median time to progression of 18 weeks and median survival of 37.17 weeks. Conclusions The survival of patients with glioblastoma multiforme remains disappointing. Multimodal therapy does not se...
International journal of clinical pharmacology research, 2003
A new schedule with cisplatin and gemcitabine administered biweekly was prospectively evaluated i... more A new schedule with cisplatin and gemcitabine administered biweekly was prospectively evaluated in stage IIIB or IV non-small cell lung cancer. We report the interim analysis of the safety and efficacy with the first 23 patients included. The mean age was 60. Thirteen patients (56.5%) were stage IIIB and 10 (43.5%) were stage IV The overall response rate was 47.8%: 69.2% for stage IIIB and 20% for stage IV The median survival among the 23 patients was 33 weeks and 1-year survival was 39%: 53.8% for stage IIIB and 20% for stage IV Seventy-seven cycles (154 administrations) were given. The mean number of cycles/patient was 3.3 (range: 1 to 6). Of the 154 administrations, 26 were delayed 1 week for recovery from toxicity. The dose intensity (Hryniuk criteria) was 94% of the planned dose. There was one toxic death with grade 4 thrombocytopenia and grade 4 esophagitis. In two patients, grade 3-4 vascular toxicity was observed, with distal arterial ischemic changes in the lower extremitie...
Docetaxel and irinotecan chemotherapy have shown good efficacy in the treatment of advanced oesop... more Docetaxel and irinotecan chemotherapy have shown good efficacy in the treatment of advanced oesophago-gastric cancer. This randomised phase II study evaluated the efficacy and toxicity profile of two non-platinum docetaxel-based doublet regimens in advanced oesophago-gastric cancer. Chemotherapy-naïve patients with advanced oesophago-gastric cancer were randomised to receive either 3-weekly DI (docetaxel 60 mg m(-2) plus irinotecan 250 mg m(-2) (Day 1)) or 3-weekly DF (docetaxel 85 mg m(-2) (Day 1) followed by 5-fluorouracil 750 mg m(-2) per day as a continuous infusion (Days 1-5)). A total of 85 patients received DI (n=42) or DF (n=43). The primary endpoint was overall response rate (ORR). The ORR and time to progression (TTP) in the evaluable population (n=65) were 37.5% (DI) vs 33.3% (DF), and 4.2 months vs 4.4 months, respectively. In the intent-to-treat population, the observed ORR, TTP and median overall survival were similar between the two groups. Grade 3-4 neutropenia, febr...
In an attempt to increase the dose intensity of cisplatin and gemcitabine given to patients with ... more In an attempt to increase the dose intensity of cisplatin and gemcitabine given to patients with stage IIIB or IV nonsmall cell lung cancer without increasing toxicity, we have studied a biweekly administration schedule. We analyze the safety and efficacy of this treatment. Methods and Patients: In this study, cycles of 50 mg/m 2 cisplatin with 2500 mg/m 2 gemcitabine were given on days 1 and 15 every 28 days. The median age of the 49 patients was 62 years and 23 were in stage IIIB patients (46.9%), whereas 26 (53.1%) were in stage IV. Results: Overall response rate was 38.8%, 52.2% for stage IIIB and 26.9% for stage IV. Median survival was 48 weeks and 1-year survival was 44%, with 66.7% of stage IIIB patients and 13.3% of stage IV patients surviving for 1 year. In the study, 178 cycles were administered, a mean of 4 cycles per patient. The intensity of the 359 administrations reached 91.16% of the planned dosage, although 49 were delayed for 1 week while subjects recovered from the toxicity. There was 1 toxic death and 2 patients experienced vascular toxicity with distal arterial ischemic severe changes in their lower extremities. There were 7 episodes of grade 2 neutropenia, 2 of grade 3, and one of grade 4; however, no cases of febrile neutropenia were seen. The predominant nonhematologic toxic effects were asthenia and nausea/vomiting. Conclusion: The schedule of cisplatin and gemcitabine analyzed is active with a good therapeutic index.
A case of epithelioid haemangioendothelioma sited at pulmonary valve, with an excrescence growing... more A case of epithelioid haemangioendothelioma sited at pulmonary valve, with an excrescence growing invading pulmonary artery troncus and its principal branches, in a 56-year-old woman is reported. The evolutive behavior simulated some clinical situations which made difficult the diagnosis: a mild-moderate pulmonary stenosis, a general syndrome, and, finally, an acute pulmonary thromboembolism that carried to an aggressive management which conducted to the entity diagnosis.
Purpose To assess the activity of induction chemotherapy followed by surgery in stage IIIA and se... more Purpose To assess the activity of induction chemotherapy followed by surgery in stage IIIA and selected stage IIIB non–small-cell lung cancer patients. Patients and Methods Mediastinoscopy proof of either positive N2 (IIIA) or T4N0-1 (IIIB) disease was required. Induction therapy was three cycles of cisplatin/gemcitabine/docetaxel, followed by surgery. Results From December 1999 to March 2003, 136 patients were entered onto the study; the clinical response rate in 129 assessable patients was 56%. The overall complete resection rate was 68.9% of patients eligible for surgery (72% of stage IIIA patients and 66% of stage IIIB patients) and 48% of all assessable patients. Eight (12.9%) of 62 completely resected patients had a pathologic complete response. Seven patients (7.8%) died during the postoperative period. The median overall survival time was 15.9 months, 3-year survival rate was 36.8%, and 5-year survival rate was 21.1%, with no significant differences in survival between stage...
Cancer and cisplatin-based chemotherapy both are well recognized risk factors for coagulation dis... more Cancer and cisplatin-based chemotherapy both are well recognized risk factors for coagulation disorders and thrombosis. However, vascular events (VEs) seldom are considered adverse effects of treatment and may not even be taken into account in reports of chemotherapy trials. VEs were recorded prospectively in a population of patients with nonsmall-cell lung carcinoma (NSCLC) who were treated consecutively with cisplatin and gemcitabine using a diagnostic flow chart based on a thorough clinical examination, hematologic and coagulative parameters, and imaging assessments when appropriate. From January, 2000 to January 2003, 108 patients with Stage III-IV NSCLC underwent chemotherapy and were evaluated. Overall, 22 VEs occurred in 19 patients (17.6%; 95% confidence interval [95% CI], 10.3-24.8%), including 10 arterial VEs (2 myocardial infarctions, 7 lower limb arterial thrombosis, and 1 ischemic stroke) and 12 venous VEs (3 catheter-related upper limb VEs, 6 venous thrombosis of the lower limb, and 3 pulmonary embolisms). The cumulative proportion of VEs at 1 year after the start of chemotherapy was 22.0% (95% CI, 12.7-31.3%). Four patients died due to the VE (overall mortality, 3.7%), and 3 patients needed surgical revascularization. In the other patients, conservative medical treatment was effective. Baseline patient-related and disease-related characteristics of the patients with VEs did not differ significantly from the characteristics of patients without VE; liver and brain metastases were more frequent in patients with VE, although the difference did not reach statistical significance. Response rates were similar in the two groups. A double VE was detected in three patients who were given further chemotherapy after resolution of the first event. VEs were a common finding in chemotherapy-treated NSCLC patients. Chemotherapy itself seem to be a powerful risk factor for VE. Strategies to predict the occurrence of VEs should be developed to spare this life-threatening toxicity.
Discoidin domain receptor 2 (DDR2) is arising as a promising therapeutic target in breast carcino... more Discoidin domain receptor 2 (DDR2) is arising as a promising therapeutic target in breast carcinoma (BC). The ability of DDR2 to bind to collagen promotes protumoral responses in cancer cells that influence the tumor microenvironment (TME). Nonetheless, the interrelation between DDR2 expression and TME modulation during BC progression remains poorly known. For this reason, we aim to evaluate the correlation between intratumoral expression of DDR2 and the infiltration of the main TME cell populations, cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs). First, collagen and DDR2 expression levels were analyzed in human invasive BC samples. Then, DDR2 status correlation with tumor aggressiveness and patient survival were retrieved from different databases. Subsequently, the main pathways, cell types, and tissues correlated with DDR2 expression in BC were obtained through bioinformatics approach. Finally, we studied the association of DDR2 expression with the r...
13509 Background: AC is indicated for stage III and high risk stage II colon cancer, as well as f... more 13509 Background: AC is indicated for stage III and high risk stage II colon cancer, as well as for stages II-III rectal cancers combined with RT. Moreover, chemotherapy improves survival in metastatic disease. There are no randomised trials evaluating the role of systemic AC after resection of metastases from CRC. Methods: We retrospectively reviewed patients with completely (R0) removed HM and/or PM from CRC, analysing prognostic factors for overall survival, including AC. Kaplan-Meier method with log rank test was used to assess and compare survival curves. Cox regression model was applied for multivariate analysis. Results: From Jan 1993 to Jun 2004, 146 patients were identified: 98 (67%) with HM, 39 with PM (27%) and 9 (6%) with both HM and PM. Gender (M/F): 102/44. Median age: 65.5 y-o (39.3–82.6). Primary CRC: rectum 62 (42.5%), pN+ 87 (60%), stage IV at diagnosis 57 (39%). Number of metastatic nodules resected: mean 2.25 (1–10). Size of the largest metastasis: mean 4 cm (0.5...
15516 Background: Concomitant CRT has become a standard treatment for advanced head and neck canc... more 15516 Background: Concomitant CRT has become a standard treatment for advanced head and neck cancer. The aim of this study was to evaluate the efficacy and toxicity of concurrent CRT with D in patients (pts) with advanced squamous cell carcinoma of head and neck (SCCHN). Methods: Patients with untreated and unresectable stage III or IV (M0) squamous cell carcinoma of head and neck were included. Treatment consisted of D 20 mg/m2 weekly with concomitant radiotherapy 70 Gy (2 Gy per day, 7 weeks). Results: From September 03 to October 05, sixty-four pts with advanced SCCHN, were recruited. Gender: 61 male, 3 female. Mean age: 56.5 years old (range 42–77). ECOG PS 0/1/2: 0/57/7. Primary sites of disease: oral cavity 8, oropharynx 26, hypopharynx 15 and larynx 15. Stage III 16 pts and stage IV 48 pts. Compliance: 393 administrations of D were given, median 6, mean 6 (range 1–8). Fifty-five pts (86%) completed the radiotherapy dose planned (mean dose of RT was 66 Gy). One refused more tr...
17093 Background: Firstly, we conducted a phase I of a biweekly schedule of cisplatin with prolon... more 17093 Background: Firstly, we conducted a phase I of a biweekly schedule of cisplatin with prolonged infusion of gemcitabine (10 mg/m2/min) and stablished the dose to perform a phase II. We present final results of a phase II with this combination. Methods: Patients with cytologically or histologically confirmed NSCLC stage IIIB and IV were included. Treatment consisted of Cisplatin 50 mg/m2 days 1 and 15 with Gemcitabine 1600 mg/m2 in 160 minutes (10 mg/m2/min), days 1 and 15 every 28 days. Chemotherapy was administered to a maximum of 6 cycles; if radiotherapy was planned, patients received 4 cycles. Results: From March-04 to January-05, 55 patients were included. Patient characteristics: Median age 59 years (35–75). Gender: 51 male 4 female. ECOG performance status 0/1/2: 8/43/4. Histology: Squamous cell carcinoma 26 (47.3%), adenocarcinoma 22 (40%), large cell carcinoma 2 (3.6%), undifferentiated 5 (9%). Stage: IIIA 2 (3.6%), IIIB 27 (49.1%) and IV 26 (47.3%). Treatment complian...
Aims and Background The objective of the study was to evaluate the efficacy of combined chemoradi... more Aims and Background The objective of the study was to evaluate the efficacy of combined chemoradiation in patients with newly diagnosed glioblastoma multiforme. The main end points were time to progression and overall survival. Methods Thirty-one patients with glioblastoma multiforme underwent surgery whenever possible and then received intravenous VM26 (120 mg/m2) and oral CCNU (120 mg/m2) for three cycles followed by radiotherapy (60 Gy). Results Surgery consisted of a complete resection in 39% of patients, partial resection in 35% and a biopsy in 26%. Sixteen patients had clinical or radiological evidence of progression during or after chemotherapy. Hematologic toxicity was mild. Forty-five percent of patients received the scheduled dose of radiation. The outcome was disappointing, with a median time to progression of 18 weeks and median survival of 37.17 weeks. Conclusions The survival of patients with glioblastoma multiforme remains disappointing. Multimodal therapy does not se...
International journal of clinical pharmacology research, 2003
A new schedule with cisplatin and gemcitabine administered biweekly was prospectively evaluated i... more A new schedule with cisplatin and gemcitabine administered biweekly was prospectively evaluated in stage IIIB or IV non-small cell lung cancer. We report the interim analysis of the safety and efficacy with the first 23 patients included. The mean age was 60. Thirteen patients (56.5%) were stage IIIB and 10 (43.5%) were stage IV The overall response rate was 47.8%: 69.2% for stage IIIB and 20% for stage IV The median survival among the 23 patients was 33 weeks and 1-year survival was 39%: 53.8% for stage IIIB and 20% for stage IV Seventy-seven cycles (154 administrations) were given. The mean number of cycles/patient was 3.3 (range: 1 to 6). Of the 154 administrations, 26 were delayed 1 week for recovery from toxicity. The dose intensity (Hryniuk criteria) was 94% of the planned dose. There was one toxic death with grade 4 thrombocytopenia and grade 4 esophagitis. In two patients, grade 3-4 vascular toxicity was observed, with distal arterial ischemic changes in the lower extremitie...
Docetaxel and irinotecan chemotherapy have shown good efficacy in the treatment of advanced oesop... more Docetaxel and irinotecan chemotherapy have shown good efficacy in the treatment of advanced oesophago-gastric cancer. This randomised phase II study evaluated the efficacy and toxicity profile of two non-platinum docetaxel-based doublet regimens in advanced oesophago-gastric cancer. Chemotherapy-naïve patients with advanced oesophago-gastric cancer were randomised to receive either 3-weekly DI (docetaxel 60 mg m(-2) plus irinotecan 250 mg m(-2) (Day 1)) or 3-weekly DF (docetaxel 85 mg m(-2) (Day 1) followed by 5-fluorouracil 750 mg m(-2) per day as a continuous infusion (Days 1-5)). A total of 85 patients received DI (n=42) or DF (n=43). The primary endpoint was overall response rate (ORR). The ORR and time to progression (TTP) in the evaluable population (n=65) were 37.5% (DI) vs 33.3% (DF), and 4.2 months vs 4.4 months, respectively. In the intent-to-treat population, the observed ORR, TTP and median overall survival were similar between the two groups. Grade 3-4 neutropenia, febr...
In an attempt to increase the dose intensity of cisplatin and gemcitabine given to patients with ... more In an attempt to increase the dose intensity of cisplatin and gemcitabine given to patients with stage IIIB or IV nonsmall cell lung cancer without increasing toxicity, we have studied a biweekly administration schedule. We analyze the safety and efficacy of this treatment. Methods and Patients: In this study, cycles of 50 mg/m 2 cisplatin with 2500 mg/m 2 gemcitabine were given on days 1 and 15 every 28 days. The median age of the 49 patients was 62 years and 23 were in stage IIIB patients (46.9%), whereas 26 (53.1%) were in stage IV. Results: Overall response rate was 38.8%, 52.2% for stage IIIB and 26.9% for stage IV. Median survival was 48 weeks and 1-year survival was 44%, with 66.7% of stage IIIB patients and 13.3% of stage IV patients surviving for 1 year. In the study, 178 cycles were administered, a mean of 4 cycles per patient. The intensity of the 359 administrations reached 91.16% of the planned dosage, although 49 were delayed for 1 week while subjects recovered from the toxicity. There was 1 toxic death and 2 patients experienced vascular toxicity with distal arterial ischemic severe changes in their lower extremities. There were 7 episodes of grade 2 neutropenia, 2 of grade 3, and one of grade 4; however, no cases of febrile neutropenia were seen. The predominant nonhematologic toxic effects were asthenia and nausea/vomiting. Conclusion: The schedule of cisplatin and gemcitabine analyzed is active with a good therapeutic index.
A case of epithelioid haemangioendothelioma sited at pulmonary valve, with an excrescence growing... more A case of epithelioid haemangioendothelioma sited at pulmonary valve, with an excrescence growing invading pulmonary artery troncus and its principal branches, in a 56-year-old woman is reported. The evolutive behavior simulated some clinical situations which made difficult the diagnosis: a mild-moderate pulmonary stenosis, a general syndrome, and, finally, an acute pulmonary thromboembolism that carried to an aggressive management which conducted to the entity diagnosis.
Purpose To assess the activity of induction chemotherapy followed by surgery in stage IIIA and se... more Purpose To assess the activity of induction chemotherapy followed by surgery in stage IIIA and selected stage IIIB non–small-cell lung cancer patients. Patients and Methods Mediastinoscopy proof of either positive N2 (IIIA) or T4N0-1 (IIIB) disease was required. Induction therapy was three cycles of cisplatin/gemcitabine/docetaxel, followed by surgery. Results From December 1999 to March 2003, 136 patients were entered onto the study; the clinical response rate in 129 assessable patients was 56%. The overall complete resection rate was 68.9% of patients eligible for surgery (72% of stage IIIA patients and 66% of stage IIIB patients) and 48% of all assessable patients. Eight (12.9%) of 62 completely resected patients had a pathologic complete response. Seven patients (7.8%) died during the postoperative period. The median overall survival time was 15.9 months, 3-year survival rate was 36.8%, and 5-year survival rate was 21.1%, with no significant differences in survival between stage...
Cancer and cisplatin-based chemotherapy both are well recognized risk factors for coagulation dis... more Cancer and cisplatin-based chemotherapy both are well recognized risk factors for coagulation disorders and thrombosis. However, vascular events (VEs) seldom are considered adverse effects of treatment and may not even be taken into account in reports of chemotherapy trials. VEs were recorded prospectively in a population of patients with nonsmall-cell lung carcinoma (NSCLC) who were treated consecutively with cisplatin and gemcitabine using a diagnostic flow chart based on a thorough clinical examination, hematologic and coagulative parameters, and imaging assessments when appropriate. From January, 2000 to January 2003, 108 patients with Stage III-IV NSCLC underwent chemotherapy and were evaluated. Overall, 22 VEs occurred in 19 patients (17.6%; 95% confidence interval [95% CI], 10.3-24.8%), including 10 arterial VEs (2 myocardial infarctions, 7 lower limb arterial thrombosis, and 1 ischemic stroke) and 12 venous VEs (3 catheter-related upper limb VEs, 6 venous thrombosis of the lower limb, and 3 pulmonary embolisms). The cumulative proportion of VEs at 1 year after the start of chemotherapy was 22.0% (95% CI, 12.7-31.3%). Four patients died due to the VE (overall mortality, 3.7%), and 3 patients needed surgical revascularization. In the other patients, conservative medical treatment was effective. Baseline patient-related and disease-related characteristics of the patients with VEs did not differ significantly from the characteristics of patients without VE; liver and brain metastases were more frequent in patients with VE, although the difference did not reach statistical significance. Response rates were similar in the two groups. A double VE was detected in three patients who were given further chemotherapy after resolution of the first event. VEs were a common finding in chemotherapy-treated NSCLC patients. Chemotherapy itself seem to be a powerful risk factor for VE. Strategies to predict the occurrence of VEs should be developed to spare this life-threatening toxicity.
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Papers by Ramon Barcelo