Biomedical subjects

P Kosmidis

Publications and source records attributed to P Kosmidis.

140 records · Page 8Linked to original sources

PubMedDate not supplied

A randomized trial comparing adjuvant fluorouracil, epirubicin, and mitomycin with no treatment in operable gastric cancer.

Combination chemotherapy (CT) has, in some groups of patients with gastric cancer (GC), who are at a high risk for relapse, resulted in a small but measurable improvement in palliation and patient survival not reaching statistical significance and therefore remaining applicable in an investigational setting. Based on the above data, we studied adjuvant CT with FEM (5-fluorouracil (5-FU), epirubicin, mitomycin C) in a randomized study of patients with completely resected stage III GC and patients with stages T1-3 with a low histologic grade. CT was started 2-3 weeks after surgery. From August 1988 until February 1994, 84 patients with completely resected tumors and lymph nodes were randomized to either group A (FEM) or group B (no treatment). Patients were eligible for randomization if they had a Karnofsky score > 60, no postoperative evidence of residual tumor, and normal cardiac, hepatic and renal functions. Forty-two patients were randomized to each group, with no significant differences regarding: age distribution, group A 53 years (41-65), group B 57 years (35-66); sex, group A 32/10, group B 25/17 (men/women); site of primary tumor, group A 22/20, group B 25/17 (pylorus/antrum); histologic grade, group A 0/19/23, group B 0/25/17 (grades I/II/III); lymph node metastases, group A 30, group B 32, and surgical procedure, group A 33/9/6, group B 35/7/9 (total gastrectomy/partial gastrectomy/splenectomy). Group A received 5-FU 600 mg/m2/day i.v. on days 1, 8, 29 and 36, epirubicin 45 mg/m2/day i.v. on days 1 and 29, and mitomycin C 10 mg/m2 i.v. on day 1. The schedule was repeated every 56 days for 3 cycles. Group B received no treatment odd was only subjected to the regular follow-up. At the last follow-up at 66 months, 27/42 patients in group A (64%) had relapsed or died, compared to 34/42 patients in group B (81%). The differences in the relapse and the disease-free and the overall survival rates were not statistically significant. Only the subgroup of patients with histologic grade III tumors receiving adjuvant FEM demonstrated a trend towards improved survival (p = 0.085). Main therapy-related toxicities for the treatment group were grade I-II anemia, neutropenia, and throbocytopenia in 16, 45, and 22% of patients, respectively, and grade I-II nausea and vomiting in 29% of patients. Based on the present findings and those of previous studies, even if one considers the difference reaching statistical significance in the latter for histologic grade III tumors, it becomes evident that with current therapeutic modalities adjuvant therapy has no established role in the management of resectable GC. Studies of new-generation regimens, such as FAMTX (5-FU, Adriamycin and methotrexate) as well as ELF (etoposide, Leucoverin, and 5-FU), should be conducted in the adjuvant therapy setting with a nontherapy control group, in order to clarify the issue of adjuvant CT in resectable GC.

Adult↗

PubMedDate not supplied

A randomized open-label parallel-group study comparing ondansetron with ondansetron plus dexamethasone in patients with metastatic breast cancer receiving high-dose epirubicin. A Hellenic Cooperative Oncology Group study.

AIMS AND BACKGROUND: The purpose of this multicenter randomized, open-label, parallel-group study was to assess whether the addition of low-dose dexamethasone to ondansetron results in improved control of chemotherapy-induced emesis in patients undergoing first-line chemotherapy with high-dose epirubicin. METHODS & STUDY DESIGN: Patients were randomized to receive either 24 mg of ondansetron or 24 mg of ondansetron plus 8 mg of dexamethasone administered as an intravenous infusion 30 minutes prior to administration of chemotherapy. Both groups of patients received 8 mg of ondansetron given orally from day 2 to 5 two times daily. Fifty-three patients received ondansetron and 50 received ondansetron plus dexamethasone. The patients recorded nausea and the number of vomits and retches daily on diary cards. RESULTS: Significantly more patients in the ondansetron plus dexamethasone group experienced neither vomiting nor retching during the first day of the first course of chemotherapy compared to those receiving ondansetron alone (79.6% vs 53.8%, P = 0.0062). Furthermore, there was a trend in favor of ondansetron plus dexamethasone in the control of nausea. There was no statistically significant difference between ondansetron plus dexamethasone versus ondansetron alone in protecting patients from emesis between days 2 and 5 of the first course of chemotherapy (66.7% vs 62.7%, P = 0.68). This was probably due to the small sample size. Ondansetron was well tolerated, with 15 patients (15%) reporting adverse events such as headache or constipation. CONCLUSIONS: It appears that ondansetron given intravenously in combination with dexamethasone is more effective than ondansetron alone in the control of acute emesis in patients undergoing their first course of chemotherapy with high-dose epirubicin. No difference between the regimens was found with regard to nausea and delayed emesis control.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

Radiation and concurrent carboplatin administration in locally advanced head and neck cancer. A Hellenic Cooperative Oncology Group Study.

AIMS AND BACKGROUND: To improve local control in patients with locally advanced inoperable head and neck cancer we administered carboplatin concurrently with radiation. METHODS: Thirty-nine patients entered the study. There were 35 men and 4 women with a median age of 58 years (range, 24-74) and a median performance status of 90 (range, 60-100) of the Karnofsky scale. The primary site included nasopharynx (5 patients), oropharynx (n = 10), hypopharynx (n = 5), larynx (n = 12), oral cavity (n = 2), paranasal sinuses (n = 3), salivary glands (n = 1) and unknown (n = 1). Histology was squamous cell carcinoma in all cases. All patients were irradiated with a 60Co unit. According to the protocol, they should receive 66-70 Gy to the tumor area and 45 Gy to the tumor-free area of the neck. Carboplatin was administered at a dose of 400 mg/m2 on days 2, 22 and 42. RESULTS: Totally, 112 cycles of carboplatin were administered, of which 106 (95%) were at full dose. Median dose intensity of carboplatin actually delivered was 170 mg/m2/week (range, 57-200). All patients were irradiated, although only 30 (77%) received > 66 Gy. After the completion of combined treatment, 23 (59%, 95% C.I. 42-74%) achieved a CR and 10 (26%, 95% C.I. 13-42%) a PR. Grade 3-4 myelotoxicity was noticed in 60% of the patients. Other grade 3-4 toxicities included stomatitis (13%), dysphagia (5%) and weight loss (3%). Median time to progression was 18 months (range, 2-25). CONCLUSIONS: Radiation and concurrent administration of carboplatin determined a high CR rate in patients with HNC, although the superiority of this combined modality approach over radiation alone has to be proven in phase III trials.

Adult↗

PubMedDate not supplied

Carcinoembryonic antigen (CEA), alpha-fetoprotein, CA 19.9 and CA 125 in advanced colorectal cancer (ACC).

In 111 patients with ACC we studied CEA, FP, CA-125 and CA 19.9 during therapy and follow-up. Marker determination was performed every two months. CEA was elevated (> 5 ng/ml) in 82%, alpha FP (> 15 ng/ml) in 0%, CA-125 (> 38 U/ml) in 37%, CA 19.9 (> 30 U/ml) in 64% of the patients. We did not find significant differences between the sensitivity of CEA alone and that of the combination of CEA + CA-125 (86%), CEA + CA 19.9 (87%), CA-125 + CA-19.9 (71%) and CEA + CA-125 + CA 19.9 (88%). We did not find any correlation between the level of positivity of the markers and the clinical parameters we examined. When serial determinations were carried out, CEA showed the best indication of response to treatment, followed by CA 19.9. In the evaluation of the response to chemotherapy we found that CA 125 presented significant percentages of false-positive (9%) (P < 0.008) and false-negative (8.1%) (P < 0.008) results, compared to CEA and CA 19.9. CA 125 did not demonstrate any utility for the follow-up of patients with colorectal cancer although increased values were found in 37%. We conclude that CEA is currently the best marker for the follow-up of patients with colorectal cancer. The combination of CEA and CA 19.9 had some utility in follow-up, without significantly improving CEA results.

Adenocarcinoma↗

PubMedDate not supplied

Factors that influence the antiemetic activity of metoclopramide to cisplatin based chemotherapy.

Some clinical parameters play a role in developing effective antiemetic therapy. In the present study, 310 patients entered and 301 were evaluable. They received cisplatin based combination chemotherapy (100 mg/m2), with antiemetic therapy based in metoclopramide, at a standard dose and schedule (2 mg/kg in 5 doses). Patient characteristics such as age, sex, performance status (Karnofsky), site of primary tumor, weight loss >15%, previous chemotherapy, previous radiotherapy, history of vomiting during pregnancy, additional drugs (dexamethasone, alprazolam), in the antiemetic regimen were included in the evaluation. We also studied the manifestation of anxiety and depression and the presence of psychosocial problems related to therapy, evaluated them with specific psychological indexes modified for our study. We evaluated incidence of vomiting, retches, and nausea, with several scales. We distinguished three groups of factors influencing nausea and vomiting. Factors that predicted for increased nausea and vomiting was gender (women), stress and age (younger patients experienced more prolonged duration and higher grades of nausea). The addition of alprazolam (a sedative drug) and dexamethasone, was associated with decreased incidence of nausea and vomiting. The weight loss (increased nausea and decreased vomiting control according to Gralla's scale). Previous chemotherapy decreased the number of patients without nausea and vomiting control according to Gralla's scale. Patients with previous radiotherapy presented an increased grade of nausea. Patients with head and neck cancer presented less nausea with shorter duration, less frequent episodes of vomiting. Patients with ovarian cancer presented increased mean number of retches. In conclusion, despite difficulties in assessing nausea and vomiting among clinical trials, several factors, especially stress, gender, weight loss, additional drugs (corticosteroids and sedatives) may play an important role in modulating the antiemetic response.

Adult↗

PubMedDate not supplied

Parameters that influence the outcome of nausea and emesis in cisplatin based chemotherapy.

Some factors have demonstrated an influence on emesis and antiemetic response. In order to study these factors, 306 patients (pts) entered this study receiving cisplatin based combination chemotherapy (CT) (100 mg/m3, with ondansetron (8 mg, 3 times daily for 4 days) as the only antiemetic treatment. Known factors that influence the result of antiemetic therapy such as age, sex, performance status (Karnofsky), site of primary tumor, weight loss, anxiety, depression, psychological problems related to CT (psychological PRC) etc, were included in the evaluation. We evaluated the number of vomits, retches and nausea. The existence of psychological PRC was found to be a prominent factor for the development of nausea and emesis, being at the same time strongly associated with scaling variables (Gralla, retching and nausea grading) used to measure the severity of nausea and emesis (p = 0.001). Stress was also a significant predictor; patients with stress had an almost two times higher probability to develop nausea or retching compared to patients without stress indications (p = 0.001), while the occurrence of retching was marginal. Younger patients (less than 40 years old) were found to be almost three times more susceptible to retching compared to older patients (more than 40 years old) (P 0.006). With all possible evaluations, we concluded that significant factors are psychological PRC, stress and age. In conclusion, three factors, age, stress and psychological PRC, should be taken seriously into consideration in the design of future trials evaluating antiemetic treatment, as well as in the every-day clinical practice, in order to provide patients with a better quality of life during emetogenic CT.

Adult↗

PubMedDate not supplied

First line combination chemotherapy with docetaxel and vinorelbine in advanced breast cancer. A phase II study.

UNLABELLED: We evaluated the efficacy and tolerance of the combination of docetaxel and vinorelbine as first line treatment in metastatic breast cancer (MBC). These agents have different mechanisms of action and both are active in advanced breast cancer. Thirty-nine chemotherapy-naive for metastatic disease patients were treated on an out-patient basis with vinorelbine 20 mg/m2 i.v. on days 1 and 8 and docetaxel 85 mg/m2 i.v. on day 8, every 3 weeks. Twenty-one (53.8%) patients had locoregional disease, 30 (76.9%) had distant metastases and 20 (51.3%) had visceral metastases. The intent-to-treat objective response rate (RR) was 48.75% (19 out of 39 patients; 95% confidence interval (CI), 32.4% to 65.2%). Four patients (10.25%) achieved a complete response (CR) (95% CI, 2.9% to 24.2%) and 15 (38.5%) a partial response (PR) (95% CI, 23.4% to 55.4%). The median duration of response was 4 months, the median time to progression (TTP) was 6 months and the median survival-time was 11.3 months. Grade 3 and/or 4 (3/4) anemia and thrombocytopenia occurred in 7.7% and 5.1% of patients, respectively. Twelve (30.7%) patients developed grade 3/4 neutropenia and 7 (17.9 %) were complicated with fever. Grade 3/4 diarrhea, nausea-vomiting, fatigue and constipation were not a problem. Alopecia was universal. Grade 3/4 neurotoxicity was evident in 2.6% of patients. None of the patients developed allergic reaction or fluid retention. There was one treatment-related death due to grade 4 neutropenia and sepsis. CONCLUSION: This combination of docetaxel and vinorelbine, a non-anthracycline-containing regimen, is a moderately effective regimen for the treatment of chemotherapy-naive breast cancer patients with metastases, causing only mild to moderate toxicity.

Adult↗

PubMedDate not supplied

Prognostic factors in Greek patients with small cell lung cancer (SCLC). A Hellenic Cooperative Oncology Group study.

BACKGROUND: Prognostic factors among Greek patients with SCLC were evaluated. PATIENTS AND METHODS: Data from 516 patients with SCLC treated by the Hellenic Cooperative Oncology Group were analyzed. Multivariate analysis was performed. RESULTS: Complete response (CR) was achieved in 26.8% and partial response in 40.1% of patients. The median duration of response was 7.4 months, the median survival 10.5 months and the 2-year survival rate 12%. The stage of the disease was a dominant prognostic factor for survival and response. PS 0-1 was a major prognostic factor for survival, duration of response and CR. Female gender was a favorable predictor for CR. Superior vena cava syndrome was a poor prognostic factor for survival and duration of response. Weight loss and age > or = 60 were poor predictors for response. The sites of metastases affected survival, duration of response and response. Normal alkaline phosphatase was a favorable prognostic factor for survival, duration of response and response. Normal lactate dehydrogenase and thoracic irradiation were favorable prognostic factors for survival and duration of response.

Adult↗

PubMedDate not supplied

Non-small cell lung cancer in the young: a retrospective analysis of diagnosis, management and outcome data.

BACKGROUND: Non-small cell lung cancer (NSCLC) in young patients is uncommon and is thought to constitute a distinct oncological entity with characteristic clinicopathological patterns. Since the reported data are scant and discordant, the presentation, management and outcome data of NSCLC patients aged under 45 years of age were analyzed and compared with those of patients over 45 years old. Prognostic factors for risk classification were also evaluated. MATERIALS AND METHODS: The data were abstracted from the Hellenic Cooperative Oncology Group (HeCOG) cancer registry database. The presentation, management and outcome data of patients with histologically confirmed NSCLC, managed from 1989 until 2004 in HeCOG participating centers, were retrospectively analyzed. The clinicopathological characteristics of patients aged < and > than 45 years old were compared and evaluated for prognostic significance regarding outcome. RESULTS: The data for NSCLC patients (1906), of whom 115 were aged <45, were retrieved. In comparative analysis, the young patients were more frequently asymptomatic at diagnosis, while older patients presented significantly higher rates of thoracic pain, cough and fatigue (p<0.01). The young patients were more commonly diagnosed with adenocarcinoma and less frequently with squamous cancer than patients aged over 45. Although the stage distribution was distinct, with older patients presenting higher rates of stage IV disease (21.9% vs. 12.2%), the rates of early lung cancer (stages I-IIIa) were similar. The overall survival (OS) was not significantly different (median OS 12 vs. 11.5 months, p=0.277). Among patients who underwent first-line palliative chemotherapy, young individuals had a significantly shorter time to progression: 4.3 vs. 5.8 months (p=0.0049). Univariate and multivariate regression analyses established the prognostic usefulness of the performance status, disease stage and disease-free interval for the risk of death, both in the total number of patients (1906) and in young patients (115). CONCLUSION: This large retrospective series failed to present strong evidence that NSCLC among young individuals constitutes a distinct clinicopathological entity with differing biological behavior, since the same clinicopathological prognostic factors were valid in both age groups. Molecular phenotypic studies are needed to shed light on this controversial subject.

Adult↗

PubMedDate not supplied

High-dose leucovorin, fluorouracil and oral dipyridamole in the treatment of advanced colorectal cancer.

Fifty-five patients with advanced colorectal cancer were treated with the combination of leucovorin (LV), fluorouracil (FU) and dipyridamole (DP). Two (4%) patients achieved a clinical complete remission, 4 (7%) a partial remission, 24 (44%) had stable disease while 25 (45%) patients progressed during the chemotherapy period. Median survival was 47 weeks and median time to progression 19.5 weeks. Major toxicities included diarrhea (66%), leukopenia (45%), anemia (50%) and nausea/vomiting (44%). In conclusion, the addition of oral DP does not appear to improve the efficacy of the standard LV/FU regimen in patients with advanced colorectal cancer.

Adenocarcinoma↗

PubMedDate not supplied

Combination chemotherapy with cisplatin and/or doxorubicin in malignant mesothelioma. A retrospective study [corrected from prospective].

From June 1984 to October 1995, forty seven consecutive patients (pts) with a confirmed diagnosis of diffuse malignant mesothelioma (MM) of the pleura (41) and peritoneum (6), were treated with cisplatin (CDDP) (24 pts) (Group A), or Doxorubicin (ADM) (14) based chemotherapy (Group B), or a combination of CDDP and ADM (9 pts) (Group C). Chemotherapy for Group A was CDDP 100 mg/m2 Dl with Viblastine 6 mg/m2 Dl, 8 (24 pts) for Group B ADM 40 mg/m2 D I with Vincristine (VCR) 2 mg Dl and DTIC 200 mg/m2 Dl-3 (5 pts) or instead of DTIC Cyclophosphamide 600 mg/m2 Dl instead (pts 4). A Total of 11/47 (23%) of the pts responded to chemotherapy; Group A: I complete and 5 partial responders, Group B: 3 partial responders and Group C: 2 partial responders. Pts with MM of peritoneum showed I complete (Group A) and 4 partial (Group B: 2, Group B: 1, Group C: I) responses, a total of 5/6 (83%). There was no difference in survival time, duration of response and time to progression between the examined groups. A statistically significant difference between responders and non responders in terms of survival was seen: responders 20.8 (3-35), non-responders 5.05 (1-12) months (P = 0.03). Toxicity was acceptable and no treatment-related deaths occurred. Myelo-suppression, mild anemia, nausea-vomiting, anorexia and fatigue were the main toxicities. We conclude that CDDP or ADM-based chemotherapy or a combination of both drugs are equally effective in MM.

Adult↗

PubMedDate not supplied

Prognostic variables in greek patients with stage II breast cancer: a Hellenic Cooperative Oncology Group study.

The independent effects of several patient, tumor and treatment-related prognostic factors on relapse-free survival (RFS) and overall survival (OS) were assessed by Cox multivariate regression analysis in 988 Greek patients with stage II breast cancer. At a median follow-up time of 83 (range 3.3-131+) months and after the evaluation of all patients together, the number of positive axillary nodes (p < 0.0001), tumor size (p = 0.0024) and tumor grade (p = 0.0008) were identified as significant prognostic factors for RFS. Also, the number of positive nodes (p < 0.0001), tumor size (p = 0.0002) and ER status (p = 0.0001) were found to be significant for OS. These short-term prognostic variables are similar to those reported for this group of patients in other European countries and in the USA.

Adult↗

PubMedDate not supplied

Prognostic factors influencing complete response to treatment and survival of patients with nasopharyngeal cancer.

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 be significant for OS (p = 0.005 and p = 0.013, respectively). The present study has shown that major prognostic factors influencing the outcome of our patients with NPC are similar to those reported in recent Chinese studies. These prognostic factors may be used as stratification factors in randomized clinical trials.

Adolescent↗

PubMedDate not supplied

Bcl2 and p53 protein expression in metastatic carcinoma of unknown primary origin: biological and clinical implications. A Hellenic Co-operative Oncology Group study.

We have previously shown that metastatic carcinomas of unknown primary site overexpress several tumor markers as well as the products of the oncogenes c-myc, ras and c-erbB2. We analyzed the tissue expression of the protein products of the apoptosis modulation genes p53 and bcl-2 in 47 CUP cases. Formalin-fixed, paraffin embedded tumor specimens were stained with commercially available antibodies to p53 (DO7) and bcl-2 after antigen retrieval by the microwave method. Staining was evaluated by intensity (1+ to 3+), percentage of positive cells (1-100%), and the 'intensity times percentage' product defined as the immunoreactivity index with values ranging from 0 to 300. Immunoreactivity index values higher than 150 were considered to characterize protein over-expression. Expression of p53 was identified in 70.2% of tumors while 53% of them showed a high immunoreactivity index. Bcl-2 expression was detected in 65% of tumors and overexpressed in 40%. Overexpression of both proteins was detected in 20% of tumors. The detection of either protein was not associated with any of the major clinicopathological variables studied. Nevertheless, a trend towards a more favourable response to platin based chemotherapy was seen in the cases that showed a strong expression of both proteins, when analysed by immunoreactivity index and percentage of positive cells. We conclude that CUP overexpress at a high percentage the p53 and the bcl2 proteins. The observed weak association of strong expression of these proteins with response to platin-based chemotherapy deserves further evaluation in the CUP setting.

Adenocarcinoma↗