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P Kosmidis

Publications and source records attributed to P Kosmidis.

At least 127 records · Page 7Linked to original sources
PubMed1991

Platinum-based chemotherapy followed by radiation therapy of locally advanced nasopharyngeal cancer. A retrospective analysis of 39 cases.

A retrospective analysis was performed of 39 patients with locally advanced nasopharyngeal cancer treated with combined chemotherapy and radiation therapy during the last five years at our departments. There were 26 men and 13 women with median age 55 (24-75) years. Histology was squamous cell carcinoma in 6 patients and undifferentiated carcinoma in the remaining 33 patients. Induction chemotherapy consisted of either regimen A (cisplatin 100 mg/m2 day 1, 5-FU 1,000 mg/m2 days 2-6 as continuous infusion, bleomycin 15 mg days 15 and 29 i.m., mitomycin 4 mg/m2 day 22 and hydroxyurea 1,000 mg/m2 daily days 23-27) or regimen B (carboplatin 300 mg/m2 day 1, 5-FU 1,000 mg/m2 days 1-5 as continuous infusion and methotrexate 1.2 g/m2 day 14 with leucovorin rescue). After completion of induction chemotherapy 13 patients (33%) had complete remission (CR) and 19 (49%) partial remission (PR). The CR rate was increased after radiation therapy to 72%. Survival rates were 88% at 12 and 78% at 24 months. Median time to progression was 29.5 months. In conclusion, induction chemotherapy with a platinum-based regimen followed by radiation therapy achieved a high rate of local control. If the treatment also prolongs survival must, however, be studied by randomized trials.

Adenocarcinoma↗
PubMed1990

Folinic acid plus high-dose 5-fluorouracil with allopurinol protection in the treatment of advanced colorectal carcinoma.

Protection by prolonged administration of allopurinol against high-dose 5-fluorouracil (5-FU) administered with folinic acid in 74 patients with colorectal cancer was investigated. The dose of 5-FU was 700 mg/m2 per day for 5 days. Of 41 patients without previous chemotherapy, 1 had a complete response and 4 had partial responses (total 12%), 15 remained stable and 21 progressed. Mean duration of response was 7.4 (1.8-12.6) months. The most frequent toxicities were decreased granulocytes (13%), diarrhoea (37%), and stomatitis (35%), which were similar to the frequencies of other studies with lower doses of 5-FU without allopurinol. Prolonged administration of allopurinol thus gives some protection to patients with colorectal cancer who receive folinic acid plus high-dose 5-FU but responses were not better than those with conventional doses.

Aged↗
PubMed1990

Multimodal biochemical modulation of 5-fluorouracil activity in advanced colorectal cancer with allopurinol, folinic acid and dipyridamol.

It is now commonly accepted that the activity of 5-fluorouracil (5FU) may be potentiated by folinic acid (FA). Moreover dipyridamol (DIP) interacts with the pyrimidine salvage pathway of 5FU. In 28 patients with advanced colorectal cancer, in progression under FA-5FU, we continued treatment with FA-5FU plus DIP. FA 200 mg/m2/day. i.v. push was given before 5FU 766.52 mg/m2/day (mean dose), in 60 min infusion for 5 subsequent days. Cycle was repeated every 21 days. We noticed greater but not seriously increased toxicity by the addition of DIP. The addition of DIP did not change response rates; it seemed to increase response but not significantly.

Allopurinol↗
PubMed1990

A randomized trial of the effect of three non-steroid anti-inflammatory agents in ameliorating cancer-induced fever.

Paraneoplastic fever is well known, and is not an uncommon problem in daily practice. In an effort to ameliorate tumour-induced fever we randomized 48 patients to receive three different non-steroid anti-inflammatory drugs: Naproxen (500 mg d-1), Indomethacin (75 mg d-1) or Diclophenac sodium (75 mg d-1). All patients had solid tumours, and microbial infection had been excluded. All three drugs were equally effective in bringing the temperature down to normal for a period of 30-33 d. Naproxen had the most rapid effect. In cases of fever relapse with the first drug, when the other two drugs were given instead, both proved equally effective. No side-effects were observed. We conclude that Naproxen, Indomethacin and Diclophenac sodium are equally effective in ameliorating paraneoplastic fever. In relapse, a second drug given subsequently can be effective as well.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Association of neutrophil alkaline phosphatase activity and glycosylated haemoglobin in diabetes mellitus.

We determined neutrophil alkaline phosphatase (NAP) activity in diabetic patients in conjunction with HbA1c levels. NAP was estimated using semiquantitative cytochemical technique, and we studied its activity in different groups of diabetic patients. We found that NAP score is correlated with the HbA1c level. Non-diabetic patients were used as controls, in whom NAP score and HbA1c were found normal. In diabetic patients the NAP activity and the HbA1c level were altered similarly during the various phases of the disease. Our findings indicate that NAP score could be used as a simple new parameter for diabetes. The pathophysiologic mechanism of our observations needs further investigation.

Alkaline Phosphatase↗
PubMed1988

Reduction of oral toxicity of 5-fluorouracil by allopurinol mouthwashes.

5-Fluorouracil (5-FU) is the most effective drug in gastrointestinal cancer. Mucositis and bone marrow toxicity are the two major limiting side effects. In our effort to reduce mucositis we administered 'Allopurinol' mouthwash in 16 patients who had experienced oral mucositis during prior treatment with 5-FU. In all patients significant reduction of oral toxicity was noticed as well as prolonged pain relief. This observation must be tested by controlled clinical trial.

Allopurinol↗
PubMedDate not supplied

Subcutaneous low doses of interleukin-2 and recombinant interferon alpha with carboplatin and vinblastine in patients with advanced melanoma.

Twenty-three patients with advanced melanoma were treated with a combination of subcutaneous recombinant human interleukin-2 (IL-2), and recombinant interferon alpha-2a (IFN-alpha) with chemotherapy consisting of four cycles of carboplatin (300 mg/m2, day 1) and vinblastine (6 mg/m2, day 1), every 28 days (CV-IL-IF). IL-2 was given at a dose of 4.5 x 10(6) U twice daily on days 3-6 and days 21-24 of each cycle; IFN-alpha dose was 4.5 x 10(6) U, starting on day 2, thrice weekly. Immunotherapy was intended to continue for 6 months. Of the 23 analyzed patients, 4 (17%) achieved an objective response, including 1 complete and 3 partial responses, in nonvisceral metastatic disease. The median time to progression was 5 months and the median survival from onset of the treatment 6 months (range 1-14 months). Four patients discontinued the treatment, due to nonhaematologic toxicity; 3 for severe weakness and the 4th patient for long-lasting CNS side-effects. Other grade 3-4 toxicities included weight loss (22%), nausea and vomiting (17%) and alopecia (13%). The haematologic toxicity was acceptable. No toxic death was noted. It is concluded that the CV-IL-IF regimen has limited activity and moderate toxicity.

Adult↗
PubMedDate not supplied

Diffuse large cell lymphomas: identification of prognostic factors and validation of the International Non-Hodgkin's Lymphoma Prognostic Index. A Hellenic Cooperative Oncology Group Study.

Several clinical prognostic factors have been identified that predict treatment outcome in patients with diffuse large cell lymphomas. An International Non-Hodgkin's Lymphoma Prognostic Index (IPI) has been recently formulated. We tried to identify the clinical prognostic factors that predict treatment outcome in Greek patients with diffuse large cell lymphomas and validated the IPI in these patients. The possible prognostic variables for tumor response, relapse-free (RFS) and overall survival (OS) were analyzed in 239 consecutive patients treated with anthracycline-based chemotherapy regimens. In univariate analysis, factors associated with poor response were stages III-IV, performance status (PS) >/=2, spleen and bone marrow involvement, more than one extranodal site involved, increased lactate dehydrogenase (LDH) value, hemoglobin (Hb) <12 g/dl, albumin <3.5 g/dl, erythrocyte sedimentation rate (ESR) >50 mm/h. Multivariate analysis identified stage, PS, more than one extranodal site involved, increased LDH level, and ESR > 50 mm/h as the factors more predictive of poor response. For RFS, multiple Cox analysis found stages III-IV and bone marrow involvement to be statistically significant. For OS, multiple Cox analysis identified stage III-IV, PS >/=2, bone marrow involvement, more than one extranodal site involved, increased LDH level and ESR > 50 mm/h as negative prognostic factors. Patients stratified in the different risk groups of the IPI had a significantly different outcome regarding complete response (CR) rate, RFS and OS. In conclusion, although age >60 years was not recognized as an adverse factor in this analysis, our patients stratified in the different groups of the IPI had significant differences in CR rate, 2-year RFS and OS verifying the prognostic significance of the index. Bone marrow involvement and ESR > 50 mm/h, parameters that are not included in the IPI, adversely affected survival.

Adult↗
PubMedDate not supplied

Combination regimen with carboplatin, epirubicin and etoposide in metastatic carcinomas of unknown primary site: A Hellenic Co-Operative Oncology Group Phase II Study.

The encouraging results that have been reported for cisplatin combination chemotherapy in a minority of patients with cancer of unknown primary (CUP) together with the previously shown equal activity of carboplatin in this setting, prompted us to investigate the effectiveness of a carboplatin-containing regimen in a phase II clinical trial. Sixty-two evaluable CUP patients entered the protocol. The chemotherapy regimen consisted of carboplatin 300 mg/m2 IV D1, epirubicin 45 mg/m2 IV D1 and etoposide 120 mg/m2 IV D1-3 (CEE regimen) administered every 3 weeks. The median age of the patients was 61 years and 36 were male. Thirty-one diagnosed as poorly differentiated carcinomas (pdc) and the rest as adenocarcinomas. By clinicopathological criteria, 14 patients had a predominately nodal disease with pdc or poorly differentiated adenocarcinomas (pda), 3 women peritoneal carcinomatosis, and the remaining 46 patients had a predominately splanchnic involvement (24 pdc, 22 pda). Twenty-three patients responded to chemotherapy with 4 (6.5%) complete and 19 (30.5%) partial responders (RR 37%, 95% CI 25-49%). An equal activity of the regimen was observed between the two major histopathological types, the pdc and the adenocarcinomas. Nevertheless, significant differences were seen when the CEE regimen was assessed for its activity in the distinct clinicopathological subsets of CUP. Patients with predominately nodal disease of midline distribution with pdc or pda, and women with peritoneal carcinomatosis, achieved a response rate of 64 and 62% respectively, as compared with a 26% response rate for those with predominately splanchnic involvement. Overall median survival was 10 months and for patients with midline distribution 15 months. The regimen was well tolerated. It is concluded that CEE is a relatively nontoxic chemotherapy regimen and easily administered on an outpatient basis. This prospective phase II study confirmed the activity of carboplatin in the chemosensitive subsets of the predominately nodal disease of midline distribution and peritoneal carcinomatosis in women in the CUP syndrome.

Adult↗
PubMedDate not supplied

Dose-dense adjuvant chemotherapy with epirubicin monotherapy in patients with operable breast cancer and >/=10 positive axillary lymph nodes. A feasibility study.

Forty-one patients with operable breast cancer and >/=10 positive axillary lymph nodes were treated with 6 cycles of dose-dense adjuvant chemotherapy consisting of epirubicin (100 mg/m2) every 2 weeks with G-CSF support. A total of 240 cycles were administered, all of them at full dose and 19 (8%) with a delay. Thirty-eight (93%) patients completed the treatment according to the protocol. The relative dose intensity of epirubicin was 0.99. Grade 3 toxicities included anemia (3%), nausea and vomiting (5%) and alopecia (71%). After a median follow-up of 40 months, 16 (39%) patients were free of relapse. In conclusion, the present study has shown that the administration of dose-dense chemotherapy with epirubicin is feasible in the adjuvant setting with minimal toxicity.

Adult↗
PubMedDate not supplied

A randomized comparative study of antiemetic prophylaxis with ondansentron in a single 32-mg loading dose versus 8 mg every 6 h in patients undergoing cisplatin-based chemotherapy.

In several studies a single dose of 32 mg was compared to an ondansentron (OND) administration schedule of every 6 h, yielding no differences in overall efficacy. The aim of this randomized comparative study was to identify differences of these two schedules on an hour-to-hour control of nausea and vomiting, during the first 24 h in patients receiving cisplatin (CDDP)-based chemotherapy. One hundred ten patients were randomly assigned to two groups (A and B); all received combination chemotherapy with CDDP at a dose of 100 mg/m2. OND was administered as follows: group A: 8 mg, 30 min before the infusion of CDDP, and repeated every 6 h after the first dose (totally 4 doses) in the first 24 h, and group B: 32 mg before CDDP, as a loading dose and this was the total dose for the first 24 h. No overall difference was noticed during the first 24 h, as well as the next 3 days from the infusion of CDDP in the intensity of vomits, vomits without gastric content (retches), and nausea. In a more detailed monitoring of the distribution of emetic episodes during the first 24 h, there were important differences between these two antiemetic schedules: for group A an increased vomiting with or without gastric content between midnight and 6 p.m. was observed, and for group B between 6 p.m. and midnight (vomits with p 0.03, and without gastric content p 0.02). Preloading with the total 24-hour dose of OND 32 mg exhibits a more potent antiemetic activity during the initial 18 h, becoming weaker over the last 5 h of the first day, whereas the every-6-hour schedule leaves periods of poor emesis control between dosing intervals.

Adult↗
PubMedDate not supplied

Efficacy of ondansetron treatment with different timing schedules: a randomized double-blind study.

The purpose of this study was to determine whether preloading administration of ondansetron given 12.5 h before cisplatin therapy, every 6 h, is better in controlling acute cisplatin-induced emesis than a standard dose every 8 h. All patients had previously received three cycles of CDDP-based chemotherapy in a dose of 100 mg/m2. Ondansetron was given according to two schedules: in group A (40 patients) at a dose of 8 mg in 100 ml normal saline over 10 min by intravenous infusion before the infusion of CDDP continued with 1 tablet of 8 mg after 8 and 16 h; in group B (40 patients) it was administered in six intravenous doses (every 6 h) starting 12.5 h before cisplatin administration. During the following 3 days, patients from both groups continued with tablets of 8 mg orally, every 8 h in group A and every 6 h in group B. The only difference in terms of the antiemetic response noticed between the two groups was in the number of patients that presented with nausea, which was increased in group A (32) in comparison to group B (25; p < 0.022). No difference was found in the number of vomiting episodes, retches or control of emesis, during the 3-day evaluation period after cisplatin infusion, and in secondary side effects. In conclusion the total dose of 24 mg ondansetron during the acute phase of emesis is as effective as preloading and increasing the total dose to 32 mg.

Adult↗
PubMedDate not supplied

Cyclophosphamide, mitoxantrone, fluorouracil versus conventional CMF as adjuvant treatment in node-positive breast cancer patients. A Hellenic Cooperative Oncology Group Study.

362 evaluable node-positive patients with stage II breast cancer were randomized, receiving either 6 cycles of conventional CMF or 6 cycles of the combination of cyclophosphamide (500 mg/m2), mitoxantrone (Novantrone 10 mg/m2), and fluorouracil (500 mg/m2; CNF). After a median follow-up of 51 months, 64 (36%) patients relapsed in the CMF group and 60 (33%) in the CNF group (p=0.8276). By Cox multivariate analysis, tumor size, menopausal status and number of involved nodes were retained as independently significant variables. Toxicities were remarkably similar in both groups. It appears that after a median follow-up of 51 months there is no significant difference in relapse-free survival between node-positive patients with breast cancer who received either 6 cycles of the conventional CMF or the CNF combination as adjuvant treatment.

Adult↗
PubMedDate not supplied

Phase II study of 5-fluorouracil and interferon-gamma in patients with metastatic colorectal cancer. A Hellenic Cooperative Oncology Group Study.

Preclinical data have shown a synergism between 5-fluorouracil and interferon-gamma against human colon carcinoma cell lines. We conducted a phase II trial of this combination in 34 patients with metastatic colorectal cancer. 5-Fluorouracil was administered as an intravenous bolus of 500 mg/m2 weekly and interferon-gamma subcutaneous injection at a dose of 200 micrograms (6 x 10(6) IU) 3 times a week. Thirty-two patients were evaluable for response. There was one complete and two partial responses (response rate 9.0%, 95% CI 1.98-25.02%). Eleven patients (34%) had stable disease. Common toxicities included fever 81%, nausea/vomiting 19%, diarrhea 16%, flu-like syndrome 16%, malaise 12.5% and leukopenia 12.5%. These results indicate that the above combination of 5-fluorouracil and interferon-gamma has an unimpressive activity in patients with advanced colorectal carcinoma. Toxicity was very tolerable.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

First-line chemotherapy of advanced breast cancer with a combination of mitoxantrone, methotrexate, and vincristine (MIMO).

Fifty-one patients with advanced breast cancer entered a prospective study of combination chemotherapy, consisting of mitoxantrone (10 mg/m2), methotrexate (30 mg/m2), and vincristine (1 mg/m2, MIMO) given intravenously every 21 days. None of the patients had received prior chemotherapy for metastatic disease, although 24 had been previously given adjuvant chemotherapy. Forty-seven patients were analyzed for response and toxicity. Objective response was observed in 20 of them (42%) with 3 complete responses (6%) stable disease in 7 (15%), and progression in 19 (40%). Best responses were achieved in lung metastases. Liver metastases did not respond. The median duration of response was 9 months and the median time to disease progression 11 months. Toxicity was mild. Nausea and myelotoxicity were the main side effects. MIMO was found to be an effective and well tolerated first-line treatment for advanced breast cancer. The regimen was compared historically with MIMO plus carboplatin. The two types of treatment were found equipotent, with MIMO being less toxic.

Adult↗
PubMedDate not supplied

Treatment of renal cell carcinoma with escalating doses of alpha-interferon.

Forty-one patients with advanced renal cell cancer started treatment with recombinant alpha-interferon intramuscularly, beginning at a dose of 5 x 10(6) U x 3/week, progressively increasing doses every week, from 5 x 10(6) U x 3/week to 10 x 10(6) U x 3/week, to the highest dose of 15 x 10(6) U x 3/week. No complete response was achieved, partial response was achieved in 6 (13%) patients with a median duration of 45.2 (13-134) weeks. The majority of side effects from interferon treatment evaluated according to WHO classification were seen during the first 2 months and they were fever (after interferon administration) in 95% patients, chills (51%), flu like syndrome (65%), fatigue (87%), anorexia (80%), worsening in performance status (56%), nausea and vomiting (19%), weight loss (> 10% during therapy) (26%), leukopenia (14%), anemia (75%), neurological symptoms (43%), psychological symptoms (19%) and dyspnea (9%). The results are similar to other studies and toxicity was only moderate.

Adult↗
PubMedDate not supplied

Comparison of different schedules of ondansetron (GR 38032F) administration during cisplatin-based chemotherapy: a randomized trial.

The purpose of our study was to evaluate different schedules of ondansetron administration in cisplatin-induced emesis. All patients had previously received 2 cycles of CDDP-based chemotherapy in a dose of 100 mg/m2. Ondansetron was given by two schedules. Group A (45 patients) received a dose of 1 ampoule of 8 mg in 100 ml normal saline in a 10-min intravenous infusion before the infusion of CDDP; this was continued by 1 tablet of 8 mg in the afternoon and 1 before sleeping on the first day. For the next 3 days, the patients received 3 tablets of 8 mg daily. In group B (45 patients) the same doses were used at the same time and by the same route as in group A, except on the first day when all the dosages were intravenous. Nausea persisted for a longer time (A = 177 +/- 271 min, B = 78 +/- 83 min, p < 0.022), and it was intenser in group A (grade 0, p < 0.036, grade 1, p < 0.050) in comparison with group B. More patients of group B achieved complete (p < 0.015) and minor (p < 0.050) control of emesis, on the other hand group A presented an increased number with major (p < 0.015) and failure (p < 0.069) of control of emesis. There was no difference in nausea and vomiting for the next 3 days nor any difference in secondary side effects. We conclude that the intravenous administration schedule has shown superior antiemetic efficacy in patients who received cisplatin during the first 24 h.

Administration, Oral↗