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P Kosmidis

Publications and source records attributed to P Kosmidis.

At least 91 records · Page 5Linked to original sources

Combined transarterial targeting locoregional immunotherapy-chemotherapy for patients with unresectable hepatocellular carcinoma: a new alternative for an old problem.

The prognosis for patients with advanced (stage III and IV) hepatocellular carcinoma (HCC) remains poor. Liver resection and liver transplantation have limited effects on overall survival. Our study was carried out to assess a novel therapeutic approach, which includes transarterial locoregional chemotherapy and in vivo locoregional dual immunostimulation, in patients with unresectable HCC. A group of 20 patients with stage III and IV hepatocellular carcinoma had 10 courses (once per day) of transarterial targeted locoregional immunotherapy with interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), emulsified in a Lipiodol-Urografin mixture. The target organs were the spleen and the liver tumor itself. One course of intrahepatic locoregional targeting transarterial chemotherapy was given 10 days after completion of immunotherapy (mitomycin C, carboplatin, Farmorubicin, Leucovorin, 5-fluorouracil, and IFN-gamma). This was followed after 2 months by another course of transarterial targeted locoregional immunotherapy-chemotherapy. All patients survived the operation and had a mean survival time of 18 months (4-22 months). There was a decrease in the tumor size of 14 of the 20 patients. Serum alpha-fetoprotein (AFP) levels declined in 14 patients, reaching normal levels in 12 patients. These preliminary results indicate that combined locoregional immunotherapy-chemotherapy is a promising therapeutic approach in patients suffering from advanced nonresectable HCC and merits further evaluation.

Aged↗

5-Fluorouracil, folinic acid and cisplatin in advanced colorectal cancer: a pilot study.

The combination of 5-fluorouracil (5-FU) and folinic acid (FA) has demonstrated activity in colorectal cancer (CC). Cisplatin is reported to have synergistic activity with 5-FU. We examined the combination FA + 5-FU + cisplatin in patients who had previously received chemotherapy with FA + 5-FU and relapsed. Two months after the last dose of FA + 5-FU and documentation of relapse, patients continued with the regimen consisting of cisplatin 20 mg/m2 in 15 min i.v. infusion followed by FA 500 mg/m2 in 1 h i.v. infusion, in the middle of which 5-FU 500 mg/m2 i.v. bolus was administered, with adequate post-hydration. This was repeated weekly for 4 weeks followed by a 2 week rest, for a maximum of six cycles. A total of 30 patients with CC that had relapsed to the combination of FA + 5-FU were treated; 23 had previous surgery and none had radiotherapy. Local recurrence was found in eight patients, metastases in the liver in 21, in lymph nodes in six, lung six and peritoneal metastases in seven. Seven patients responded partially. Toxicity requiring dose reduction or discontinuation of treatment included neutropenia 42% (grade 3:7%), mucositis 28% (grade 1:2), diarrhea 63% (Grade 3:10%), nausea-vomiting 55% (Grade 3:10%), increased creatinine value in three patients and peripheral neuropathy in two patients. We conclude that evaluation of this regimen shows substantial toxicity, with satisfactory response as a second line chemotherapy in these heavily pretreated patients.

Aged↗

The prognostic significance of immune changes in patients with renal cancer and melanoma treated with interferon-alpha 2b.

We evaluated the response rate and the immunorestorative properties of subcutaneously administered interferon-alpha 2b (IFN-alpha 2b) in patients with advanced renal cell carcinoma (RCC) and melanoma (MEL) and correlated the immune status with clinical responses. Thirty-five patients with advanced RCC and 12 with MEL were treated with recombinant IFN-alpha 2b. The dose was increased progressively from 5 x 10(6) IU the first week to 10 x 10(6) IU the second week and thereafter 15 x 10(6) IU subcutaneously. The response rate for RCC patients was as follows: (1) 6 patients achieved partial responses; (2) 9 patients had stable disease, and (3) 20 patients progressed. The response rate for patients with MEL was as follows: (1) 4 patients experienced partial response and (2) 8 patients progressed. In all patients blood was withdrawn prior to IFN treatment and then monthly. T lymphocytes after isolation from peripheral blood were tested for proliferation in the autologous mixed lymphocyte reaction (auto-MLR), and allogeneic mixed lymphocyte reaction (allo-MLR), interleukin-2 production (IL-2prod), expression of IL-2 receptors (IL-2rec) during the allo-MLR, and interleukin-1 production (IL-1prod) by peripheral blood monocytes. Striking increases were demonstrated in all parameters 1 month after treatment with IFN-alpha 2b. Patients with RCC experiencing a partial response showed a mean increase of 50% in the auto-MLR, 95% in the allo-MLR, 62% IL-2prod, 88% IL-2rec and 76% in IL-1prod.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Renal Cell↗

A comparative study with two administration schedules of leucovorin and 5-fluorouracil in advanced colorectal cancer.

One hundred and seven previously untreated patients with measurable metastatic colorectal cancer who were treated with 5-fluorouracil (5FU) and leucovorin (LV) in two different maximum doses and schedules were retrospectively analyzed. Group A, 52 pts, was treated with LV 200 mg/m2/D i.v. push, followed by 5FU 700 mg/m2/D i.v. 1 h infusion for 5 D. Cycle was repeated every 21 D. Group B, 55 pts, was treated with LV 500 mg/m2/D in a 2 h infusion and 5FU 600 mg/m2/D i.v. bolus at mid-time of LV infusion, repeated every week for 6 wk followed by 2-wk rest period. There was no difference in response (A 8%, B 11%). Median survival for A was 37 (2-131) wk, B was 59 (1-112) wk (P = 0.021), time to progression for A was 20 (0-131) wk, B 30 (0-102) wk (P = 0.021). Administered mean dose intensity of LV was 350.8 mg/m2/wk in group A and 405.0 mg/m2/wk in group B without any significant difference; that of 5FU was significantly higher in group A as compared to group B (1205.3 vs 468.9 mg/m2/wk, respectively) (p < 0.0001). This difference was a consequence of the planned dose intensity for this drug in the two treatment regimens. Toxicity was more frequent and intense in group A for mucositis (P < 0.001), fatigue (P < 0.01), and neurotoxicity (P < 0.05), and in group B for neutropenia (P < 0.001) and nausea-vomiting (P < 0.001). There were one and four iatrogenic deaths in group A and B patients, respectively (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Ondansetron versus metoclopramide as antiemetic treatment during cisplatin-based chemotherapy. A prospective study with special regard to regard to electrolyte imbalance.

Cancer patients selected for cisplatin-based chemotherapy were randomly divided into two groups (42 patients in each) which received either metoclopramide or ondansetron as antiemetics. Metoclopramide was given i.v. with 5 doses of 2 mg/kg starting 30 min before the cisplatin infusion and continued with one dose every 3 h. Ondansetron was given with a first injection of 8 mg i.v. 30 min before the cisplatin infusion; the patients were given 8 mg orally 5 and 10 h after the cisplatin infusion followed by 8 mg x 3 during the next two days. In the present study ondansetron was superior to metoclopramide concerning antiemetic efficacy and gave also less side-effects as diarrhea, dizziness, extrapyramidal symptoms and electrolyte imbalance (sodium, potassium, magnesium, phosphorous) during the first 24 h following the cisplatin infusion.

Adult↗

[Amphotericin B--bioavailability in the cornea. Studies with local administration of liposome incorporated amphotericin B].

Amphotericin B remains an important antifungal agent in the treatment of ocular mycosis. Since topical ocular application is limited because of ocular irritation and poor penetration, we studied the pharmacokinetics of amphotericin B encapsulated in unilamellar liposomes (AmBisome). One drop (20 microliters) of AmBisome or an equivalent concentration of amphotericin B was applied to rabbit eyes. Drug concentrations were measured 15, 60, 120 and 240 min following administration of the agents by HPLC in cornea and aqueous humor. The effect of intact (group A) and debrided corneal epithelium (group B) was also studied. Corneal amphotericin B levels were significantly higher (P < 0.01) after 15 min in animals receiving amphotericin B as compared to AmBisome in group A. At later time points no differences in the corneal drug levels were found, and the drug levels following AmBisome application were remarkably stable. Epithelial removal resulted in increased corneal drug levels following application of both amphotericin B preparations. Significantly higher drug levels were observed after free amphotericin B treatment at 15-60 min (P < 0.01). Drug levels in the aqueous humor did not differ between the two amphotericin B preparations and remained below therapeutically effective concentrations. These results suggest that topically delivered AmBisome provides stable corneal drug levels, but has the potential benefit of lowered ocular toxicity.

Amphotericin B↗

Ophthalmomyiasis externa due to the sheep botfly Oestrus ovis (Diptera: Oestridae) in southwest Germany.

We present a case of ophthalmomyiasis externa in a 54-year-old man in southwest Germany (Baden-Württemberg). After the patient had been attacked by a fly, he complained of a foreign-body sensation and itching in his right eye and developed purulent conjunctivitis. Slit-lamp examination revealed the presence of translucent, rapidly moving insect larvae in the conjunctival sac and on the corneal surface. Following removal of all larvae and instillation of gentamicin, the symptoms completely resolved within 2 days. Two of the nine larvae removed were examined by light microscopy and taxonomically classified as first-instar larvae of the sheep botfly Oestrus ovis L. 1758. Although this fly is the most common causative agent of external ophthalmomyiasis in the world, infestations in central Europe have only rarely been reported. Besides the case report and a detailed description of the larvae, an overview of the literature on European cases of ophthalmomyiasis externa caused by Oestrus ovis is given.

Animals↗

Evaluation of six tumor markers in patients with carcinoma of unknown primary.

We have retrospectively evaluated six serum tumor markers in 85 patients with carcinoma of unknown primary. The serum levels of carcinoembryonic antigen (CEA), CA 19-9, CA 15-3, CA 125, beta-chorionic gonadotropin (beta-HCG) and alpha-fetoprotein (AFP) were related with the histological pattern (undifferentiated carcinoma or adenocarcinoma), the number and the site of metastases, as well as the response to chemotherapy and the patients' survival. More than 40% of the patients had increased serum levels of all six tumor markers, except of AFP which was found to be increased in only 17% of them. Increased levels of CA 19-9 were related to metastatic adenocarcinoma, whereas CA 19-9 and CA 15-3 had a relationship with more advanced disease. Patients with liver involvement had higher mean levels of CEA and CA 19-9 as compared to those with nodal disease. None of these markers was found to have a predictive value for response to chemotherapy or survival. Although the present study has a retrospective nature, it allows us to conclude that patients with CUP have a nonspecific over-expression of the above serum tumor markers and that routine use of these markers does not offer any diagnostic or prognostic assistance.

Adenocarcinoma↗

Combination chemotherapy with cisplatin-vinblastine in malignant mesothelioma.

From June 1985 to March 1993, 20 consecutive patients with histologically proven malignant mesothelioma were treated with cisplatin 100 mg/m2 i.v. infusion on day 1 and vinblastine 6 mg/m2 i.v. on day 1 and 8. Treatment was repeated every 4 weeks until progression. All patients were evaluated clinically and by CT-scan and were staged (Stage IV), according to Butchard's criteria, on entry to the study. None had prior surgical excision. Eighty-one chemotherapy cycles were administered to 20 patients. One complete response, four partial responses, nine stable diseases and six progressions were noted. One partial responder entered complete response following an operation. Toxicity was acceptable and no treatment-related deaths occurred. The median survival for responders was 19.3 months; for patients with stable disease 15.7 months and for non-responders, 5.2 months. The mean duration of response was 13 months. We conclude that for this small group of patients, the combination cisplatin-vinblastine is effective, with acceptable toxicity in malignant mesothelioma. Further study with a larger number of patients is necessary.

Adult↗

The value of neuroendocrine markers in non-small cell lung cancer: a comparative immunohistopathologic study.

In order to estimate the value of immunohistochemical identification of neuroendocrine (NE) differentiation markers in non-small cell lung carcinomas (NSCLCs), we investigated the expression of five neuroendocrine and neural differentiation-related antigens in 51 NSCLCs. Additionally, 20 epithelial lung tumors with NE differentiation [15 carcinoids and five small cell lung carcinomas (SCLCs)] and 61 epithelial tumors of various other origin (breast, prostate, colon and head-neck carcinomas) were studied. An indirect two-stage immunoperoxidase method was performed in formalin-fixed and paraffin-embedded tissue specimens, by using commercially available monoclonal antibodies. These antibodies are directed against neuron-specific enolase (NSE), chromogranin-A and Leu-7 which are general markers of NE differentiation, bombesin, which is a specific NE secretory product and neurofilament triplet protein (NFTP), an intermediate filament protein of neuronal differentiation. All five markers demonstrated a positive immunoreactivity in NSCLCs, equally distributed to all three histologic subtypes, ranging from 16 to 47% of the cases (NSE 47%, bombesin 21.5%, Leu-7 21.5%, chromogranin-A 18% and NFTP 16%). Most of the carcinoids and SCLCs expressed multiple or all NE markers. The other four epithelial tumors showed a positive immunoreactivity for bombesin, Leu-7 and NFTP, ranging from 11 to 40% of the cases. Chromogranin-A was not expressed in any of these tumors, whereas NSE was demonstrated only in 17% of breast carcinomas. The following remarks can be drawn from this study: (1) some NSCLCs showed immunophenotypic NE differentiation; (2) among all the markers used, NSE was the most sensitive (sensitivity, 100%) and chromogranin-A the most specific (specificity, 100%); and (3) NSE and chromogranin-A appear to be the most valuable and useful indicators of probable neuroendocrine differentiation in lung epithelial tumors.

Antigens, CD↗

Comparison of ondansentron versus ondansentron plus methylprednisolone as antiemetic prophylaxis during cisplatin-containing chemotherapy.

We compared the antiemetic efficacy of ondansentron versus ondansentron and corticosteroids in cisplatin-induced emesis. None of our patients had received prior chemotherapy. All patients received chemotherapy including cisplatin 100 mg/m2. Forty patients received ondansentron alone (Group A) and 40 the combination of ondansentron and methylprednisolone (Group B). Ondansentron was given at a dose of 8 mg in 100 mL N/S over 10 min by intravenous infusion. The initial dose was administered before the cisplatin and was followed by 8 mg orally in the afternoon and before sleeping the first day of chemotherapy. During the next 2 days, the patients received 8 mg orally 3 times daily. Methylprednisolone was given as an intravenous bolus of 40 mg before chemotherapy and then together with each dose of ondansentron at a dose of 16 mg orally. Group A had significantly longer duration of nausea after chemotherapy than group B (117 +/- 111 min, 62 +/- 71 min, P < 0.013). The response on emesis was also improved in group B, especially the day of chemotherapy [treatment failure: group A: 13 patients (30%) versus group B: 5 patients (11.6%), P < 0.03] and the next day [complete response: group A: 17 patients (39.5%) versus group B: 30 patients (69.7%), P < 0.005]. Patients in group B presented more sedative effects (P < 0.001) and better appetite (P < 0.02) than patients in group A. There were no other significant differences in side effects (activity, headache, constipation, etc). We conclude that corticosteroids improve the antiemetic efficacy of ondansentron in cisplatin-induced chemotherapy, and should be included in antiemetic regimens.

Adolescent↗

Intensive chemotherapy with high-dose epirubicin every 2 weeks and prophylactic administration of filgrastim in advanced breast cancer.

50 women with advanced breast cancer were treated with an intensified regimen which consisted of high-dose epirubicin (110 mg/m2) every 2 weeks and filgrastim (5 micrograms/kg) subcutaneously for 13 days, starting 24 h after chemotherapy. 44 patients completed all six cycles. The median interval between cycles of treatment was 14.3 days. The actually administered median dose per unit time per patient was 53 mg/m2/week, amounting to 97.2% of the dose prescribed by the protocol. 7 [14%, 95% confidence interval (C.I.) 4-24%] patients achieved a complete and 25 (50%, 95% C.I. 36-64%) a partial response. Median time to progression was 32 weeks and median survival 64 weeks. Stomatitis and fever each occurred in 7 (14%) patients. Grade 3 haematological toxicity was observed in 6 (12%) patients. 1 (2%) patient developed grade 4 cardiac toxicity. This intensified regimen appears to be a well tolerated and effective treatment in advanced breast cancer.

Adult↗

Does substitution of surgery with induction chemotherapy preserve organ function in inoperable head and neck cancer? A retrospective analysis of 73 cases.

From August, 1984 until May, 1991, 154 patients with locally advanced head and neck cancer were treated with 3 cycles of platinum-containing induction chemotherapy followed by definitive radiotherapy. Among them, there were 32 patients with cancer of oropharynx or hypopharynx and 41 patients with cancer of larynx, who were treated with this combined approach with the intention of preserving the involved organ. After the completion of chemotherapy 5 (16%) patients with pharyngeal tumors achieved a complete response (CR) and 14 (44%) a partial response (PR). After the completion of radiotherapy the CR rate was increased to 38%. After induction chemotherapy 7 (17%) of the 41 patients with cancer of the larynx achieved a CR and 25 (61%) a PR. The CR rate was tripled (68%) following radiotherapy and salvage surgery. So far, 8 complete responders with pharyngeal and 6 with laryngeal tumors relapsed mainly locoregionally. With a minimum follow-up of 22 months, median time to progression was 8 months for patients with cancer of the pharynx and 13 months for patients with cancer of the larynx. Median survival for these two groups of patients was 13 and 24 months respectively. In patients with locally advanced cancer of the oropharynx, hypopharynx or larynx induction chemotherapy followed by radiotherapy may delay in many or even omit in a few patients the necessity of radical surgery without compromising survival.

Adult↗

A comparative study of cisplatin and vinblastine versus ifosfamide, cisplatin and vinblastine in non-operable non-small-cell lung cancer. A study of the Hellenic Co-operative Oncology Group for Lung Cancer Trials.

PURPOSE: To evaluate the efficacy and toxicity of ifosfamide in combination with cisplatin and vinblastine in non-operable non-small-cell lung cancer (NSCLC). METHODS: A total of 136 patients with stage III or IV NSCLC were randomized to either PV (cisplatin, 120 mg/m2, and vinblastine, 6 mg/m2) or VIP (PV with the addition of ifosfamide, 3 g/m2) every 3 weeks. RESULTS: Patients receiving VIP had a higher response rate (31% vs. 10%), but the performance status (PS) was significantly worse in those receiving PV. No difference in survival can be demonstrated between the two treatment groups. The median survival was 8.4 months. In both groups, patients with stage III disease, good PS and no visceral involvement had better survivals. Nausea/vomiting and alopecia were more pronounced in the VIP group, although both chemotherapies were well tolerated. CONCLUSIONS: The addition of ifosfamide improved the response rate, but a survival advantage cannot be proven. The prognostic value of stage, PS and metastatic site is confirmed in this trial; further studies are required to select subgroups of patients who may have a survival benefit with combination chemotherapy. The response rate elicited by VIP makes it a candidate for neoadjuvant treatment.

Adult↗

Randomized comparison of etoposide-cisplatin vs. etoposide-carboplatin and irradiation in small-cell lung cancer. A Hellenic Co-operative Oncology Group study.

PURPOSE: To compare the efficacy and toxicity of etoposide and cisplatin (EP) with etoposide and carboplatin (EC) in combination with irradiation in small-cell lung cancer (SCLC). METHODS: Previously untreated patients (pts) with SCLC and measurable or evaluable disease were randomized to receive either cisplatin 50 mg/m2 on days 1-2 or carboplatin 300 mg/m2 on day 1, both combined with etoposide 300 mg/m2 on days 1-3 every 21 days for 6 treatment cycles. The vast majority of responding limited disease (LD) pts and complete responders (CR) with extensive disease (ED), also received thoracic irradiation (TI) and prophylactic cranial irradiation (PCI) concurrently with the third cycle. RESULTS: Of the 147 patients registered, 143 were eligible; median performance status (PS, WHO) was 1, and tumour stage was LD in 41 pts of each treatment group. The mean delay between cycles was 8 days in the EP group and 9 in the EC group increasing in both arms with the number of treatment courses. The drug dose administered per unit time as a proportion of the protocol dose was 74% and 80% for the two groups respectively. Leukopenia, neutropenic infections, nausea, vomiting, neurotoxicity and hyperergic reactions were more frequent and/or severe in the EP group. The CR rates were 57% and 58% for EP and EC respectively. Median survival for all pts was 12.5 and 11.8 months, respectively. CONCLUSION: Both treatments proved to be effective, with no differences in response and survival between the two treatment arms. The EC regimen was associated with significantly less toxicity.

Adult↗

Comparison of ondansentron (GR 38032F) versus ondansentron plus alprazolam as antiemetic prophylaxis during cisplatin-containing chemotherapy.

The purpose of our study was to evaluate the effectiveness of alprazolam (APZ) as an adjuvant drug to ondansentron against cisplatin-induced emesis. All patients received CDDP 100 mg/m2, and had previously received chemotherapy. We established two groups of patients randomly: Group A patients received 5-HT3 alone, and Group B received 5-HT3 and APZ. The drugs were administered as follows: 5-HT3 was given at a dose of 1 ampule 8 mg in 100 ml N/S in 10 minutes i.v. infusion before the infusion of CDDP. We continued with 1 tablet 8 mg in the afternoon and 1 before sleeping the first day; for the next two days, patients received 3 tablets 8 mg/day. APZ was given in tablets of 0.25 mg 60 minutes before CDDP infusion and then with the second and third dose of 5-HT3. We did not find significant differences in clinical parameters and factors, especially anxiety, that influenced vomiting between the examined groups. The mean number of vomiting episodes without gastric content (4.76 episodes) and the mean duration of nausea (195 minutes), were greater in Group A than in Group B (1.39 episodes, p < .0001; 91 minutes, p < .049). Differences also were found in the mean number of vomiting episodes with gastric content between the examined groups (A: 1.97; B: 1.09; p < .135). The intense of nausea and vomiting according to WHO classification was greater in Group A (grade 0, p < .004; grade 2, p < .020) than in Group B. Patients of Group B had fewer problems with appetite (p < .027), and more intense sedative effect (grade 0 [p < .001], 1 [0.027], 2 [0.022]) than patients of Group A. In conclusion APZ improved the antiemetic efficacy of ondansentron in cisplatin-induced emesis.

Adult↗

Radiation therapy and concurrent cisplatin administration in locally advanced head and neck cancer. A Hellenic Co-operative Oncology Group study.

In an attempt to improve local control of locally advanced head and neck cancer, radiation therapy was combined with cisplatin. Forty-eight patients entered into this study. All patients were irradiated with a 60Co unit and according to the protocol they should receive 70 Gy in the tumor area and 45 Gy in the rest of neck. Cisplatin was administered at a dose of 100 mg/m2 on days 2, 22 and 42. Thirty-seven (80%) patients received the total radiation dose as initially planned. Thirty-four (72%) patients achieved complete and 5 (10%) partial response. Grade 3-4 toxicities included vomiting (14%), stomatitis (4%), diarrhea (2%), myelotoxicity (14%), hoarseness (4%), dysphagia (30%), weight loss (32%), nephrotoxicity (4%) and dermatitis (2%). After a median follow-up of 26 (range, 18-33) months, 16 patients have died. Among the 35 complete responders 6 later on relapsed. Median relapse-free survival has not yet been reached. Combined radiation therapy and cisplatin appears to be a highly active treatment in patients with advanced head and neck cancer as far as primary locoregional response is concerned.

Adolescent↗

First-line combination chemotherapy with mitoxantrone, methotrexate, vincristine and carboplatin (MIMOC) in advanced breast cancer.

51 patients with stage IIIB and IV breast cancer entered a prospective phase II study of combination chemotherapy that consisted of mitoxantrone (8 mg/m2) day 1, methotrexate (25 mg/m2) day 1, vincristine (1 mg/m2) day 2 and carboplatin (250 mg/m2) day 2 (MIMOC) given in a 3-weekly schedule. None had received prior chemotherapy for metastatic disease, although 16 patients were given adjuvant chemotherapy. Objective response to treatment was seen in 29 of 48 patients analysed for response (60%) with 8 complete responses (CR). 7 out of 8 patients with stage IIIB disease responded, 2 of them completely. Responses were seen in all sites but the best results were achieved in lung metastases with 50% CR. The median duration of response was 8 months and the median time to disease progression was 12 months. The main toxicity was nausea and vomiting which was severe in 20% of the patients. Other toxicities were mild. MIMOC was administered on an out-patient basis and appears to be effective as first-line treatment in advanced breast cancer.

Adult↗