Este estudo tem como objetivo apresentar uma revisão das dissertações defendidas no Programa de P... more Este estudo tem como objetivo apresentar uma revisão das dissertações defendidas no Programa de Pós-Graduação em Psicologia da Universidade Federal de Uberlândia concernentes à Psicologia da Saúde. No total, 16 dissertações foram examinadas em função de um conjunto de dimensões de análise. Os resultados possibilitam a obtenção de um panorama acerca das dissertações em q uestão e o delineamento de novas perspectivas. Sugere-se, por exemplo, a opção por temáticas relativas à Psicologia da Saúde Pública em dissertações futuras, buscando-se contribuir para a formulação de propostas para a gestão de serviços ou para o aprimoramento de intervenções em diferentes níveis de atenção. E tal sugestão se estende aos pesquisadores brasileiros em geral, pois se revela potencialmente proveitosa para o avanço da Psicologia da Saúde no país, particularmente no sentido de promover uma maior articulação entre a produção do conhecimento científico e as demandas da realidade social no contexto nacional.
During the last six years the European School of Oncology (ESO) opened an undergraduate programme... more During the last six years the European School of Oncology (ESO) opened an undergraduate programme for European medical students, aiming to further improve their oncology knowledge and clinical skills. In this endeavour a 5-day course is organized every summer at the University of Ioannina, Greece, where distinguished European oncologists introduce preselected medical students to cancer medicine. The programme includes teaching of several oncological topic regarding diagnosis and treatment of the most common tumours; interactive case presentations and discussions were also incorporated. An overall of 229 medical students, mostly from European medical schools, have been taking part to this intensive summer course, from 2004 to 2009. This article presents the detailed educational programme, the evaluation results and the outcome of the last six ESO courses; an assessment of the oncological curricula available across European faculties is also presented.
To study the phenomenon of positive urine cytology in patients with lung cancer in the absence of... more To study the phenomenon of positive urine cytology in patients with lung cancer in the absence of obvious urothelial metastases. 150 patients with small (SCLC) and non-small cell lung cancer (NSCLC) of all stages and 3 control groups were prospectively studied. Immunocytochemical study (cytokeratins 7-20, TTF1) in all positive urine specimens and chemokine profile (CXCR4, CCL21) study of the primary tumor in selected positive patients was performed. In experimental study, C57Bl/6 BALB/C mice injected with LLC lung and 4T1 mammary cancer cells were used for the detection of positive urine cytology. 11% of patients with NSCLC, 7% of patients with SCLC and none of the control group had positive urine cytology. In NSCLC, metastatic disease and high tumor burden positively correlated (p=0.01 and 0.03 respectively) with the phenomenon. In SCLC, correlation with extensive disease and multiple metastatic sites (p=0.02 and 0.04 respectively) was found. No correlation was found in either group with: age, gender, histology, performance status, line of chemotherapy, previous platinum-based chemotherapy, adrenal metastases, renal function, abnormal urinary sediment, response to chemotherapy and overall survival (p=0.9). Distinctive chemokine expression was identified in positive patients studied and was not observed in negative patients (×2 p=0.008). In the experimental study, only the LLC lung cancer cells were detected in the urine cytology of mice. This phenomenon, carrying undefined pathophysiological mechanisms, seems to characterize only patients with metastatic/extensive disease and high tumor burden. Further studies are needed to validate our preliminary chemokine expression results.
We performed a phase I study of two fixed dosing schemes of cisplatin, a DNA cross-linker, with i... more We performed a phase I study of two fixed dosing schemes of cisplatin, a DNA cross-linker, with intravenous escalating topotecan, a DNA-topoisomerase I inhibitor. 40 patients with advanced solid tumors received intravenous cisplatin at a fixed dose of either 25 mg/m2 (schedule A) or 20 mg/m2 (schedule B) daily for 3 days with standard hydration. Topotecan escalation proceeded in 0.75, 0.90, 1.0, 1.15 mg/m2 cohorts in schedule A and 1.0, 1.1, 1.2, 1.3 mg/m2 cohorts in schedule B, administered intravenously at the end of cisplatin infusion daily for 3 days, repeated every 3 weeks. Dose-limiting toxicity (DLT) consisted of protracted grade IV neutropenia, febrile neutropenia, grade IV thrombocytopenia and any grade III/IV non-hematological toxicity. Epoetin and granulocyte colony-stimulating factor support was allowed on severe myeloablation. Endpoints were the identification of maximal tolerated dose (MTD), DLT and other toxicity. The MTD was reached in cohort 25/1.15 mg/m2 in schedule A and 20/1.2 mg/m2 in schedule B. All DLT seen consisted of three episodes of febrile neutropenia and two of grade IV thrombocytopenia in schedule A, with three episodes of febrile neutropenia and one of protracted neutropenia in schedule B. Myelosuppression was substantial in all cohorts despite granulocyte colony-stimulating factor and epoetin support, peaked on the third week of treatment and resulted in administration of chemotherapy at a median of every 4 weeks. Non-hematologic toxicity was mild. The response rate was 51% with seven complete responses occurring in patients with ovarian cancer, small cell and non-small cell lung cancer and cancer of unknown primary. The recommended dose was 20/ 1.1 mg/m2 for cisplatin and topotecan on schedule B, as the number of responses and administered topotecan dose were higher in schedule B recommended dose with lower cisplatin dose, minimizing problems of nephrotoxicity and vomiting. The schedule B daily cisplatin-topotecan x 3 combination with secondary cytokine support is associated with promising activity and schedule convenience. However, substantial myelosuppression undermines its applicability in the palliative setting, stressing the need for less toxic regimens.
PURPOSE To investigate if double modulation of fluorouracil (5-FU) with leucovorin (folinic acid ... more PURPOSE To investigate if double modulation of fluorouracil (5-FU) with leucovorin (folinic acid [FA]) and interferon alfa-2b (IFN 2b) improves responses and survival in comparison to single modulation of 5-FU with FA. PATIENTS AND METHODS One hundred six patients with histologically confirmed advanced colorectal cancer, measurable disease, and without previous chemotherapy were prospectively randomized into two groups. Patients in group A received 5-FU 450 mg/m2 as an intravenous bolus in the midinfusion of FA weekly. FA was given at a dose of 200 mg/m2 in 500 mL 0.9% normal saline solution in 2-hour infusion. Patients in group B received exactly the same regimen plus IFN 2b 5 million units subcutaneously three times weekly. RESULTS All patients were well balanced in both groups regarding age, sex, performance status, number, and site of metastasis. One hundred two patients were assessable. All patients have died. There was no difference in response between the two groups (7.8% v 9...
The aim of this retrospective study was to present the epidemiological, pathological and clinical... more The aim of this retrospective study was to present the epidemiological, pathological and clinical characteristics and treatment results of Greek women with epithelial ovarian cancer (EOC). From February 1976 to December 2006, 1,791 patients had been diagnosed, treated and followed up in the participating centers of the Hellenic Cooperative Oncology Group (HeCOG). Cox-regression analysis was carried out in order to identify possible prognostic factors. The median age at diagnosis was 60 years. Seventy-five percent had a performance status (PS) of 0-1, 58.5% had a serous carcinoma, 36% had poorly differentiated tumors and 57% had International Federation of Gynecology and Obstetrics (FIGO) stage III disease. Approximately half of the patients had been subjected to a total abdominal hysterectomy, bilateral oophorectomy and omentectomy, and 80% of them had undergone optimal debulking surgery. Among 1,462 patients with advanced disease, 96% had received platinum-based chemotherapy, while...
KiSS-1 is a metastasis suppressor gene encoding a neuropeptide with potent antimetastatic activit... more KiSS-1 is a metastasis suppressor gene encoding a neuropeptide with potent antimetastatic activities in tumour cell lines. The transcriptional activity of the gene and its associations in resected breast cancer were analysed. Tumour messenger RNA (mRNA) of the KiSS1 exon I/II boundary was extracted from paraffin-embedded stage II or III node-positive breast adenocarcinomas of 272 women. KiSS1 mRNA was examined for associations with outcome, disease and molecular characteristics. Only 8 out of 272 tumours (3%) yielded detectable KiSS1 mRNA levels. There was no evidence of correlation of KiSS1 transcription with the number of involved axillary nodes, grade, hormone receptor status or tumour size. Of women with increased KiSS1 mRNA tumour levels, 87.5% were postmenopausal, whereas only 48% were postmenopausal among patients without detectable KiSS1 mRNA (p = 0.03). No association of KiSS1 transcription was found with transcription of the cell cycle-regulators HER2, VEGF, p53, BCL2, PAE...
Population pharmacokinetic-dynamic analysis was prospectively integrated in a broad phase II prog... more Population pharmacokinetic-dynamic analysis was prospectively integrated in a broad phase II program of lurtotecan (GI147211), a novel camptothecin derived topoisomerase I inhibitor, to determine the population pharmacokinetic profile in a larger population, to estimate individual pharmacokinetic parameters and to investigate relationships with clinical outcome. A sparse sampling method was applied during course one, which involved two sampling time-points. A Bayesian algorithm was used to estimate individual pharmacokinetic parameters, in particular total plasma clearance (CL) and volume of distribution. In total, samples were collected of 109 (63%) of 173 patients. Pharmacokinetic-dynamic evaluation could be carried out successfully in 85 (78%) of the sampled patients. CL of lurtotecan showed substantial variability (mean 87 +/- 28 L/h) and was of the same magnitude as in the phase I studies where full pharmacokinetic curves were used. Residual variability in the population estima...
Journal of experimental & clinical cancer research : CR, 2001
The clinical relevance of quantitative assessment of tumor-tissue expression of the bcl-2 protein... more The clinical relevance of quantitative assessment of tumor-tissue expression of the bcl-2 protein in operated stage II breast cancer was investigated in this study. Thirty-five cases were studied by immunohistochemistry for the expression of bcl-2 protein and analyzed for disease outcome. One fourth (25%) of the cases were negative and 57% demonstrated near-absolute expression of the bcl-2 protein. No association was found between immunohistochemical detection of the protein with age, hormonal receptor status and tumor grading other than between bcl-2 and estrogen receptor expression (p=0.01). An impressively positive impact of near-absolute expression of bcl-2 on clinical outcome was identified. Our results provide evidence that quantitative assessment of bcl-2 expression constitutes a new approach in early breast cancer with potential clinical implications. We consider that molecular sub-staging of patients with stage II breast cancer by level of bcl-2 expression provides addition...
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 2001
Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic r... more Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic radiation therapy (HTRT) in limited disease (LD) small cell lung cancer (SCLC) is associated with a high response rate and significant prolongation of survival. Given these results, the Hellenic Cooperative Oncology Group (HeCOG) performed a multicenter randomized phase II study in patients with LD SCLC to evaluate the timing of HTRT (early vs. late) when given concurrently with chemotherapy. To be eligible for the study, patients were required to have histologically or cytologically proven LD SCLC, confined to one hemithorax and/or ipsilateral mediastinal or supraclavicular lymphnodes and absence of pleural effusion or controlateral supraclavicular lymphnode involvement. Moreover, patients had to have a good performance status and adequate haematological, liver and renal function. Patients with LD SCLC were randomized to receive HTRT either concurrently with the first (Group A) or with t...
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 2000
GI147211 is a water-soluble synthetic analogue of camptothecin showing promising in vivo and in v... more GI147211 is a water-soluble synthetic analogue of camptothecin showing promising in vivo and in vitro antitumor activity and an acceptable toxicity profile. Between April 1995 and November 1996, 67 eligible patients with pretreated breast cancer (25 patients) and chemo-naïve colorectal (19 patients) and non-small-cell lung cancer (23 patients) were entered into three multicentric, non-randomized phase II trials. Treatment schedule consisted of intravenous GI1147211 administered at a dose of 1.2 mg/m2/day for five consecutive days every three weeks. Hematological toxicity was common with grade 3-4 neutropenia in 54% of patients and neutropenic fever together or not associated with infection in 14.5% of patients. Grade 3-4 thrombocytopenia and grade 2-4 anemia were observed in 20% and in 68% of patients, respectively. Non-hematological toxicity was generally mild to moderate and consisted mainly of gastrointestinal toxicity, asthenia and alopecia. A dose-escalation to 1.5 mg/m2/d was ...
Evolution of mixed chimerism after allogeneic bone marrow transplantation as determined on granul... more Evolution of mixed chimerism after allogeneic bone marrow transplantation as determined on granulocytes and mononuclear cells by polymerase chain reaction.
Journal of experimental & clinical cancer research : CR, 1998
Tropisetron is a novel selective antagonist of the type-3 serotonin (5-HT3) receptor, with proven... more Tropisetron is a novel selective antagonist of the type-3 serotonin (5-HT3) receptor, with proven efficacy in the control of emesis related to cancer treatment. Epirubicin in doses of > 100 mg/m2 has a high emetogenic potential. This study was designed to determine whether a single intravenous administration of tropisetron could prevent acute nausea and vomiting in patients treated with high dose epirubicin. Forty chemotherapy naive breast cancer patients treated with epirubicin at a dose of 110 mg/m2 on an outpatient basis were enrolled in the study. Tropisetron 5 mg i.v. was used as antiemetic prophylaxis. "On demand" treatment with tropisetron 5 mg p.os was used for the rescue of patients who failed on the initial i.v. dose. Complete control of acute nausea and vomiting had 62.5% (95% C.I. 47.2-77.8), partial control 15% (95% C.I. 3.8-26.2) and 22.5% (95% C.I. 9.3-35.7) insufficient control or failure. Headache was the most common adverse event reported in 3 patients...
The identification of prognostic factors influencing local control and survival of patients with ... more The identification of prognostic factors influencing local control and survival of patients with nasopharyngeal cancer (NPC) might help in pointing out those patients who would probably benefit from primary treatment. A series of 137 Greek patients with locally advanced NPC treated with chemotherapy and/or radiation were analyzed for significant prognostic factors influencing complete response (CR) to treatment, time to progression (TTP) and overall survival (OS). After the completion of treatment, 92 (67%) patients achieved CR. Logistic regression analysis revealed that only T classification was significant for CR (p = 0.0058). After a median follow-up of 5 years, 66 (48%) patients demonstrated tumor progression and 64 (47%) died. Median TTP was 25.8 months (range, 0.3-118+) and median survival 58.3 months (range, 0.3-124+). Cox proportional hazards model identified age (p = 0.024) and T classification (p = 0.009) as significant factors for TTP. These two factors were also found to...
Based on the activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton,... more Based on the activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and the significant 1-year survival rates of patients with non-small cell lung cancer treated with carboplatin, the Hellenic Cooperative Oncology Group initiated a phase II trial using both agents in patients with inoperable stage III or IV disease to investigate the efficacy and toxicity of the combination. Since July 1995, 31 patients fulfilling all eligibility criteria entered this study. All patients received paclitaxel 175 mg/m2 as a 3-hour infusion and carboplatin dosed to an area under the concentration-time curve of 7, every 3 weeks. No granulocyte colony-stimulating factor was given. Among the 29 male and two female patients, the median age was 55 years (age range, 29 to 73 years) and the median Eastern Cooperative Oncology Group performance status was 1. Most of the patients had stage IV adenocarcinoma (19) with low differentiation (15). The median number of chemotherapy c...
The efficacy and toxicity of cisplatin/etoposide and carboplatin/etoposide combinations along wit... more The efficacy and toxicity of cisplatin/etoposide and carboplatin/etoposide combinations along with thoracic irradiation were prospectively assessed in patients with small cell lung cancer. Both combinations were equally effective. However, the carboplatin/etoposide regimen caused significantly less nausea, vomiting, nephrotoxicity, and neurotoxicity, and it was easier to administer. Dose intensity and treatment delays were similar in both groups. Thoracic irradiation given concurrently with chemotherapy is feasible and seems to offer a survival advantage. The relapse rate also is lower among patients who have received radiation therapy, and recurrences tended to be outside of the lung. Overall, a survival benefit was identified for patients aged between 50 and 65 years who had limited disease, good performance status, and only one metastatic site. Prophylactic brain irradiation in a subset of patients reduced brain metastasis, but the difference did not reach significance. From this...
Este estudo tem como objetivo apresentar uma revisão das dissertações defendidas no Programa de P... more Este estudo tem como objetivo apresentar uma revisão das dissertações defendidas no Programa de Pós-Graduação em Psicologia da Universidade Federal de Uberlândia concernentes à Psicologia da Saúde. No total, 16 dissertações foram examinadas em função de um conjunto de dimensões de análise. Os resultados possibilitam a obtenção de um panorama acerca das dissertações em q uestão e o delineamento de novas perspectivas. Sugere-se, por exemplo, a opção por temáticas relativas à Psicologia da Saúde Pública em dissertações futuras, buscando-se contribuir para a formulação de propostas para a gestão de serviços ou para o aprimoramento de intervenções em diferentes níveis de atenção. E tal sugestão se estende aos pesquisadores brasileiros em geral, pois se revela potencialmente proveitosa para o avanço da Psicologia da Saúde no país, particularmente no sentido de promover uma maior articulação entre a produção do conhecimento científico e as demandas da realidade social no contexto nacional.
During the last six years the European School of Oncology (ESO) opened an undergraduate programme... more During the last six years the European School of Oncology (ESO) opened an undergraduate programme for European medical students, aiming to further improve their oncology knowledge and clinical skills. In this endeavour a 5-day course is organized every summer at the University of Ioannina, Greece, where distinguished European oncologists introduce preselected medical students to cancer medicine. The programme includes teaching of several oncological topic regarding diagnosis and treatment of the most common tumours; interactive case presentations and discussions were also incorporated. An overall of 229 medical students, mostly from European medical schools, have been taking part to this intensive summer course, from 2004 to 2009. This article presents the detailed educational programme, the evaluation results and the outcome of the last six ESO courses; an assessment of the oncological curricula available across European faculties is also presented.
To study the phenomenon of positive urine cytology in patients with lung cancer in the absence of... more To study the phenomenon of positive urine cytology in patients with lung cancer in the absence of obvious urothelial metastases. 150 patients with small (SCLC) and non-small cell lung cancer (NSCLC) of all stages and 3 control groups were prospectively studied. Immunocytochemical study (cytokeratins 7-20, TTF1) in all positive urine specimens and chemokine profile (CXCR4, CCL21) study of the primary tumor in selected positive patients was performed. In experimental study, C57Bl/6 BALB/C mice injected with LLC lung and 4T1 mammary cancer cells were used for the detection of positive urine cytology. 11% of patients with NSCLC, 7% of patients with SCLC and none of the control group had positive urine cytology. In NSCLC, metastatic disease and high tumor burden positively correlated (p=0.01 and 0.03 respectively) with the phenomenon. In SCLC, correlation with extensive disease and multiple metastatic sites (p=0.02 and 0.04 respectively) was found. No correlation was found in either group with: age, gender, histology, performance status, line of chemotherapy, previous platinum-based chemotherapy, adrenal metastases, renal function, abnormal urinary sediment, response to chemotherapy and overall survival (p=0.9). Distinctive chemokine expression was identified in positive patients studied and was not observed in negative patients (×2 p=0.008). In the experimental study, only the LLC lung cancer cells were detected in the urine cytology of mice. This phenomenon, carrying undefined pathophysiological mechanisms, seems to characterize only patients with metastatic/extensive disease and high tumor burden. Further studies are needed to validate our preliminary chemokine expression results.
We performed a phase I study of two fixed dosing schemes of cisplatin, a DNA cross-linker, with i... more We performed a phase I study of two fixed dosing schemes of cisplatin, a DNA cross-linker, with intravenous escalating topotecan, a DNA-topoisomerase I inhibitor. 40 patients with advanced solid tumors received intravenous cisplatin at a fixed dose of either 25 mg/m2 (schedule A) or 20 mg/m2 (schedule B) daily for 3 days with standard hydration. Topotecan escalation proceeded in 0.75, 0.90, 1.0, 1.15 mg/m2 cohorts in schedule A and 1.0, 1.1, 1.2, 1.3 mg/m2 cohorts in schedule B, administered intravenously at the end of cisplatin infusion daily for 3 days, repeated every 3 weeks. Dose-limiting toxicity (DLT) consisted of protracted grade IV neutropenia, febrile neutropenia, grade IV thrombocytopenia and any grade III/IV non-hematological toxicity. Epoetin and granulocyte colony-stimulating factor support was allowed on severe myeloablation. Endpoints were the identification of maximal tolerated dose (MTD), DLT and other toxicity. The MTD was reached in cohort 25/1.15 mg/m2 in schedule A and 20/1.2 mg/m2 in schedule B. All DLT seen consisted of three episodes of febrile neutropenia and two of grade IV thrombocytopenia in schedule A, with three episodes of febrile neutropenia and one of protracted neutropenia in schedule B. Myelosuppression was substantial in all cohorts despite granulocyte colony-stimulating factor and epoetin support, peaked on the third week of treatment and resulted in administration of chemotherapy at a median of every 4 weeks. Non-hematologic toxicity was mild. The response rate was 51% with seven complete responses occurring in patients with ovarian cancer, small cell and non-small cell lung cancer and cancer of unknown primary. The recommended dose was 20/ 1.1 mg/m2 for cisplatin and topotecan on schedule B, as the number of responses and administered topotecan dose were higher in schedule B recommended dose with lower cisplatin dose, minimizing problems of nephrotoxicity and vomiting. The schedule B daily cisplatin-topotecan x 3 combination with secondary cytokine support is associated with promising activity and schedule convenience. However, substantial myelosuppression undermines its applicability in the palliative setting, stressing the need for less toxic regimens.
PURPOSE To investigate if double modulation of fluorouracil (5-FU) with leucovorin (folinic acid ... more PURPOSE To investigate if double modulation of fluorouracil (5-FU) with leucovorin (folinic acid [FA]) and interferon alfa-2b (IFN 2b) improves responses and survival in comparison to single modulation of 5-FU with FA. PATIENTS AND METHODS One hundred six patients with histologically confirmed advanced colorectal cancer, measurable disease, and without previous chemotherapy were prospectively randomized into two groups. Patients in group A received 5-FU 450 mg/m2 as an intravenous bolus in the midinfusion of FA weekly. FA was given at a dose of 200 mg/m2 in 500 mL 0.9% normal saline solution in 2-hour infusion. Patients in group B received exactly the same regimen plus IFN 2b 5 million units subcutaneously three times weekly. RESULTS All patients were well balanced in both groups regarding age, sex, performance status, number, and site of metastasis. One hundred two patients were assessable. All patients have died. There was no difference in response between the two groups (7.8% v 9...
The aim of this retrospective study was to present the epidemiological, pathological and clinical... more The aim of this retrospective study was to present the epidemiological, pathological and clinical characteristics and treatment results of Greek women with epithelial ovarian cancer (EOC). From February 1976 to December 2006, 1,791 patients had been diagnosed, treated and followed up in the participating centers of the Hellenic Cooperative Oncology Group (HeCOG). Cox-regression analysis was carried out in order to identify possible prognostic factors. The median age at diagnosis was 60 years. Seventy-five percent had a performance status (PS) of 0-1, 58.5% had a serous carcinoma, 36% had poorly differentiated tumors and 57% had International Federation of Gynecology and Obstetrics (FIGO) stage III disease. Approximately half of the patients had been subjected to a total abdominal hysterectomy, bilateral oophorectomy and omentectomy, and 80% of them had undergone optimal debulking surgery. Among 1,462 patients with advanced disease, 96% had received platinum-based chemotherapy, while...
KiSS-1 is a metastasis suppressor gene encoding a neuropeptide with potent antimetastatic activit... more KiSS-1 is a metastasis suppressor gene encoding a neuropeptide with potent antimetastatic activities in tumour cell lines. The transcriptional activity of the gene and its associations in resected breast cancer were analysed. Tumour messenger RNA (mRNA) of the KiSS1 exon I/II boundary was extracted from paraffin-embedded stage II or III node-positive breast adenocarcinomas of 272 women. KiSS1 mRNA was examined for associations with outcome, disease and molecular characteristics. Only 8 out of 272 tumours (3%) yielded detectable KiSS1 mRNA levels. There was no evidence of correlation of KiSS1 transcription with the number of involved axillary nodes, grade, hormone receptor status or tumour size. Of women with increased KiSS1 mRNA tumour levels, 87.5% were postmenopausal, whereas only 48% were postmenopausal among patients without detectable KiSS1 mRNA (p = 0.03). No association of KiSS1 transcription was found with transcription of the cell cycle-regulators HER2, VEGF, p53, BCL2, PAE...
Population pharmacokinetic-dynamic analysis was prospectively integrated in a broad phase II prog... more Population pharmacokinetic-dynamic analysis was prospectively integrated in a broad phase II program of lurtotecan (GI147211), a novel camptothecin derived topoisomerase I inhibitor, to determine the population pharmacokinetic profile in a larger population, to estimate individual pharmacokinetic parameters and to investigate relationships with clinical outcome. A sparse sampling method was applied during course one, which involved two sampling time-points. A Bayesian algorithm was used to estimate individual pharmacokinetic parameters, in particular total plasma clearance (CL) and volume of distribution. In total, samples were collected of 109 (63%) of 173 patients. Pharmacokinetic-dynamic evaluation could be carried out successfully in 85 (78%) of the sampled patients. CL of lurtotecan showed substantial variability (mean 87 +/- 28 L/h) and was of the same magnitude as in the phase I studies where full pharmacokinetic curves were used. Residual variability in the population estima...
Journal of experimental & clinical cancer research : CR, 2001
The clinical relevance of quantitative assessment of tumor-tissue expression of the bcl-2 protein... more The clinical relevance of quantitative assessment of tumor-tissue expression of the bcl-2 protein in operated stage II breast cancer was investigated in this study. Thirty-five cases were studied by immunohistochemistry for the expression of bcl-2 protein and analyzed for disease outcome. One fourth (25%) of the cases were negative and 57% demonstrated near-absolute expression of the bcl-2 protein. No association was found between immunohistochemical detection of the protein with age, hormonal receptor status and tumor grading other than between bcl-2 and estrogen receptor expression (p=0.01). An impressively positive impact of near-absolute expression of bcl-2 on clinical outcome was identified. Our results provide evidence that quantitative assessment of bcl-2 expression constitutes a new approach in early breast cancer with potential clinical implications. We consider that molecular sub-staging of patients with stage II breast cancer by level of bcl-2 expression provides addition...
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 2001
Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic r... more Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic radiation therapy (HTRT) in limited disease (LD) small cell lung cancer (SCLC) is associated with a high response rate and significant prolongation of survival. Given these results, the Hellenic Cooperative Oncology Group (HeCOG) performed a multicenter randomized phase II study in patients with LD SCLC to evaluate the timing of HTRT (early vs. late) when given concurrently with chemotherapy. To be eligible for the study, patients were required to have histologically or cytologically proven LD SCLC, confined to one hemithorax and/or ipsilateral mediastinal or supraclavicular lymphnodes and absence of pleural effusion or controlateral supraclavicular lymphnode involvement. Moreover, patients had to have a good performance status and adequate haematological, liver and renal function. Patients with LD SCLC were randomized to receive HTRT either concurrently with the first (Group A) or with t...
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 2000
GI147211 is a water-soluble synthetic analogue of camptothecin showing promising in vivo and in v... more GI147211 is a water-soluble synthetic analogue of camptothecin showing promising in vivo and in vitro antitumor activity and an acceptable toxicity profile. Between April 1995 and November 1996, 67 eligible patients with pretreated breast cancer (25 patients) and chemo-naïve colorectal (19 patients) and non-small-cell lung cancer (23 patients) were entered into three multicentric, non-randomized phase II trials. Treatment schedule consisted of intravenous GI1147211 administered at a dose of 1.2 mg/m2/day for five consecutive days every three weeks. Hematological toxicity was common with grade 3-4 neutropenia in 54% of patients and neutropenic fever together or not associated with infection in 14.5% of patients. Grade 3-4 thrombocytopenia and grade 2-4 anemia were observed in 20% and in 68% of patients, respectively. Non-hematological toxicity was generally mild to moderate and consisted mainly of gastrointestinal toxicity, asthenia and alopecia. A dose-escalation to 1.5 mg/m2/d was ...
Evolution of mixed chimerism after allogeneic bone marrow transplantation as determined on granul... more Evolution of mixed chimerism after allogeneic bone marrow transplantation as determined on granulocytes and mononuclear cells by polymerase chain reaction.
Journal of experimental & clinical cancer research : CR, 1998
Tropisetron is a novel selective antagonist of the type-3 serotonin (5-HT3) receptor, with proven... more Tropisetron is a novel selective antagonist of the type-3 serotonin (5-HT3) receptor, with proven efficacy in the control of emesis related to cancer treatment. Epirubicin in doses of > 100 mg/m2 has a high emetogenic potential. This study was designed to determine whether a single intravenous administration of tropisetron could prevent acute nausea and vomiting in patients treated with high dose epirubicin. Forty chemotherapy naive breast cancer patients treated with epirubicin at a dose of 110 mg/m2 on an outpatient basis were enrolled in the study. Tropisetron 5 mg i.v. was used as antiemetic prophylaxis. "On demand" treatment with tropisetron 5 mg p.os was used for the rescue of patients who failed on the initial i.v. dose. Complete control of acute nausea and vomiting had 62.5% (95% C.I. 47.2-77.8), partial control 15% (95% C.I. 3.8-26.2) and 22.5% (95% C.I. 9.3-35.7) insufficient control or failure. Headache was the most common adverse event reported in 3 patients...
The identification of prognostic factors influencing local control and survival of patients with ... more The identification of prognostic factors influencing local control and survival of patients with nasopharyngeal cancer (NPC) might help in pointing out those patients who would probably benefit from primary treatment. A series of 137 Greek patients with locally advanced NPC treated with chemotherapy and/or radiation were analyzed for significant prognostic factors influencing complete response (CR) to treatment, time to progression (TTP) and overall survival (OS). After the completion of treatment, 92 (67%) patients achieved CR. Logistic regression analysis revealed that only T classification was significant for CR (p = 0.0058). After a median follow-up of 5 years, 66 (48%) patients demonstrated tumor progression and 64 (47%) died. Median TTP was 25.8 months (range, 0.3-118+) and median survival 58.3 months (range, 0.3-124+). Cox proportional hazards model identified age (p = 0.024) and T classification (p = 0.009) as significant factors for TTP. These two factors were also found to...
Based on the activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton,... more Based on the activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and the significant 1-year survival rates of patients with non-small cell lung cancer treated with carboplatin, the Hellenic Cooperative Oncology Group initiated a phase II trial using both agents in patients with inoperable stage III or IV disease to investigate the efficacy and toxicity of the combination. Since July 1995, 31 patients fulfilling all eligibility criteria entered this study. All patients received paclitaxel 175 mg/m2 as a 3-hour infusion and carboplatin dosed to an area under the concentration-time curve of 7, every 3 weeks. No granulocyte colony-stimulating factor was given. Among the 29 male and two female patients, the median age was 55 years (age range, 29 to 73 years) and the median Eastern Cooperative Oncology Group performance status was 1. Most of the patients had stage IV adenocarcinoma (19) with low differentiation (15). The median number of chemotherapy c...
The efficacy and toxicity of cisplatin/etoposide and carboplatin/etoposide combinations along wit... more The efficacy and toxicity of cisplatin/etoposide and carboplatin/etoposide combinations along with thoracic irradiation were prospectively assessed in patients with small cell lung cancer. Both combinations were equally effective. However, the carboplatin/etoposide regimen caused significantly less nausea, vomiting, nephrotoxicity, and neurotoxicity, and it was easier to administer. Dose intensity and treatment delays were similar in both groups. Thoracic irradiation given concurrently with chemotherapy is feasible and seems to offer a survival advantage. The relapse rate also is lower among patients who have received radiation therapy, and recurrences tended to be outside of the lung. Overall, a survival benefit was identified for patients aged between 50 and 65 years who had limited disease, good performance status, and only one metastatic site. Prophylactic brain irradiation in a subset of patients reduced brain metastasis, but the difference did not reach significance. From this...
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Papers by N. Pavlidis