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Biomedical subjects

D Skarlos

Publications and source records attributed to D Skarlos.

At least 73 records · Page 4Linked to original sources
PubMed1996

Paclitaxel and carboplatin in inoperable non-small cell lung cancer.

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 cycles was two, with a range of one to six. Among 21 patients evaluable, seven achieved a partial response, 10 had stable disease, and four had progressive disease. It is too early to evaluate nine patients. Grade 2/3 nonhematologic toxicity included alopecia (48%), neurotoxicity (3.7%), and myalgia/arthralgia (7.4%). Grade 2/3 neutropenia occurred in 11.1% of patients, whereas grade 2 thrombocytopenia was seen in only 3.7%. One patient died following complications of severe allergic reaction. In conclusion, although this study is ongoing, combination treatment using paclitaxel and carboplatin is both effective and well tolerated in patients with inoperable non-small cell lung cancer.

Adult↗
PubMed1995

High-dose epirubicin and r-met-hu G-CSF (filgrastim) in the treatment of patients with advanced breast cancer: A Hellenic Cooperative Oncology Group study.

The delivery of high-dose epirubicin in patients with advanced breast cancer usually entails serious myelotoxicity and frequent treatment delays. Concurrent administration of G-CSF probably allows the administration of epirubicin on schedule with minimal morbidity. From August 1990 to February 1992, 42 women with advanced breast cancer were treated with six cycles of epirubicin 110 mg/m2 every 4 weeks. Filgrastim 5 micrograms/kg per day for 14 days was administered subcutaneously starting 24 hours after chemotherapy. All patients had multiple metastatic sites, and 39 had visceral metastases. All cases were evaluable for response, toxicity, and survival. Treatment was delayed in only two cases. The actually administered average dose per unit time per patient amounted to 99.6% of the dose prescribed by the protocol. Two (4.5%; 95% confidence interval [C.I.] 0-16%) patients demonstrated a complete response and 14 (33%; 95% C.I. 19-49%) a partial response. Median time to progression was 31 weeks and median survival was 60 weeks. Severe granulocytopenia was seen in six patients; stomatitis and diarrhea in one patient each. Myoskeletal pain was noticed in 23 (55%) patients, while cardiac problems were reported in 3 cases. The present study shows that the prophylactic use of r-met-hu G-CSF allows the administration of high-dose epirubicin every 4 weeks with minimal morbidity and an improved quality of life.

Adult↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Cisplatin/etoposide versus carboplatin/etoposide chemotherapy and irradiation in small cell lung cancer: a randomized phase III study. Hellenic Cooperative Oncology Group for Lung Cancer Trials.

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 trial, it is concluded that carboplatin/etoposide combination therapy is highly effective and is well tolerated by patients with small cell lung cancer. In limited disease, this combination can be given concurrently with thoracic irradiation and offers a survival advantage.

Adult↗
PubMed1993

Carboplatin and oral etoposide in the treatment of patients with advanced breast cancer refractory to anthracyclines.

AIMS AND BACKGROUND: To determine the efficacy and toxicity of the carboplatin and oral etoposide combination in patients with advanced breast cancer previously treated with anthracyclines. METHODS: Twenty-seven patients were treated with a maximum of 6 cycles of carboplatin (300 mg/m2) and etoposide (200 mg/m2) every 4 weeks. Prior treatment with an anthracycline was given as adjuvant in 17 patients and as first line treatment for advanced disease in 10 patients. RESULTS: Only 12 (44%) patients completed all 6 cycles of chemotherapy. The median administered dose of carboplatin was 72 mg/m2/week and of etoposide 143 mg/m2/week. Two (7.5%) complete and 4 (15%) partial responses were observed. Both complete responses occurred in patients who received only mitoxantrone-containing adjuvant treatment, and lasted for 36 and 92+ weeks. The main toxicities included anemia (56%), leukopenia (56%), nausea/vomiting (50%) and alopecia (79%). CONCLUSIONS: The combination of carboplatin and oral etoposide is effective and should probably be considered as an alternative therapeutic option for patients with advanced breast cancer refractory to anthracyclines.

Administration, Oral↗
PubMed1992

Subsets of tumors responsive to cisplatin or carboplatin combinations in patients with carcinoma of unknown primary site. A Hellenic Cooperative Oncology Group Study.

In this retrospective analysis 48 patients with metastatic undifferentiated carcinoma, adenocarcinoma and epidermoid carcinoma of unknown origin were studied. The purpose of this analysis was to evaluate both the response rate and the toxicity of combination chemotherapy containing cisplatin or carboplatin, and to attempt to identify certain clinical subsets of patients sensitive to these drugs. Four patients were not evaluable and 13 (29.5%), eight of the 34 treated with regimens containing cisplatin and 5/14 with carboplatin-based chemotherapy, responded to treatment. Six of the 23 with undifferentiated tumours, 4/17 with adenocarcinomas and 3/8 with epidermoid cancers responded to chemotherapy. Four of 6 women with adenocarcinoma of the peritoneal cavity, 5/11 with undifferentiated carcinomas with midline distribution and 3/5 with epidermoid carcinomas of the cervical nodes responded. Seven patients achieved complete and six partial remissions. The mean duration of response was nine months; a number of patients enjoyed prolonged and/or durable remissions. Toxicity was tolerable. We conclude that: (a) both cisplatin and carboplatin are active agents in this syndrome with one-third of the evaluable patients responding, and (b) there may be chemosensitive subgroups, such as patients with peritoneal adenocarcinomatosis, undifferentiated carcinoma with midline distribution and metastatic epidermoid carcinoma of the neck nodes. The effectiveness of carboplatin in these patients and the responsiveness of metastatic epidermoid carcinoma of unknown origin have not been adequately dealt with in the literature.

Adenocarcinoma↗
PubMed1991

High-dose epirubicin as a single agent in the treatment of patients with advanced breast cancer. A Hellenic Co-operative Oncology Group study.

Fifty-two women with advanced breast cancer were treated with 6 cycles of epirubicin. Even though the study was started with a dose schedule of 110 mg/m2 every 3 weeks, the average treatment interval was 26 days and the median weekly dose 78% of the protocol requirement. Forty-eight patients were evaluable for response; 3 achieved a complete remission which lasted for 17, 24 and 65 weeks, respectively, and 14 a partial remission. Median survival was 32 weeks. Toxicity included nausea/vomiting (68%), anemia (24%), leukopenia (37%), thrombocytopenia (8%), alopecia (81%), stomatitis (24%), diarrhea (14%), fever (19%) and fatigue (14%). Also 1 treatment-related death occurred and 2 cases of arrhythmia. Monotherapy with high doses of epirubicin has definite activity in advanced breast cancer and deserves further study in combination with hematopoietic growth factors which might allow a higher dose intensity.

Adult↗
PubMed1990

Immunohistochemical and immunocytochemical study of bladder carcinomas using the epithelium-specific, tumour-associated monoclonal antibodies HMFG1 and AUA1.

The antigenic expression of normal bladder epithelium and transitional carcinomas has been studied using the epithelium-specific, tumour-associated monoclonal antibodies HMFG1 and AUA1. Tissues from 79 cases of bladder carcinoma and 11 cases of non-neoplastic bladder tissues were stained with both the haematoxylin-eosin (H/E) and the indirect two-stage immunoperoxidase methods using the monoclonal antibodies (MAbs) HMFG1 and AUA1 at a concentration of 25 micrograms ml-1. Positive and negative controls were also used. Moreover, 46 urine smears prepared after cytocentrifugation were stained with both the Papanicolaou and the indirect two-stage immunoperoxidase methods. The results showed that HMFG1 reacted with the majority of cases of grade III carcinomas and carcinomas in situ and with a subset only of low-grade (I and II) carcinomas. The pattern of staining showed the following characteristics: (1) the epithelial surface membrane stained both in normal bladder and bladder carcinomas (surface of the papillae), (2) a variant number of cancer cells, increasing with the degree of malignancy, showed membrane and/or cytoplasmic staining, (3) tumours of the same histological grade showed antigenic heterogeneity. The MAb AUA1 was not widely expressed. The immunocytochemical study confirmed the reaction of HMFG1 with a variant number of malignant urothelial cells exfoliated in urine. Their reaction with AUA1 was much more limited. The immunocytochemical staining seemed to be more sensitive in the detection of malignant cells in some cases which had been characterized as negative or suspicious for malignancy by the Papanicolaou examination. The intravesical treatment with chemotherapeutic agents did not seem to influence the antigenic expression of malignant urothelial cells.

Antibodies, Monoclonal↗
PubMed1988

Intracavitary use of two radiolabeled tumor-associated monoclonal antibodies.

Six patients with metastatic breast cancer and malignant pleural effusions and 13 patients with known or suspected ovarian cancer, underwent immunoscintigraphy after intracavitary (intrapleural or intraperitoneal) administration of iodine-131-(131I) or indium-111-(111In) labeled tumor associated monoclonal antibodies HMFG2 and H17E2. This method proved to be sensitive and specific with a true-positive result in 13 out of 14 patients with tumor and a true-negative result in five out of five patients without tumor. At any one time, 65%-80% of the whole-body radioactivity was closely associated with the cavity into which the radiolabeled antibody was administered while the radioactivity in the blood was always low, (approximately 4 X 10(-3) of administered dose/ml of blood). Concentrations of radiolabeled antibody (per gram of tumor tissue) ranged from 0.02%-0.1% of the injected dose in intracavitary tumors, but only 0.002% in a retroperitoneal metastasis. The specificity of this approach was documented in four control patients with benign ovarian cysts and in two patients who were imaged using both specific and nonspecific radiolabeled antibody. We conclude that the intracavitary administration of 131I- or 111In-labeled HMFG2 and H17E2 is a favorable route of administration and offers significant advantages over previously reported intravenous administration for the localization of breast or ovarian metastases confined to the pleural or peritoneal cavities.

Adult↗
PubMed1988

Monoclonal antibodies in ovarian tumor imaging.

Immunoscintigraphy of ovarian tumors by intraperitoneal administration of I131 HMFG2 monoclonal antibodies (mabs) was used in this study. The purpose was to evaluate the diagnostic potential of this non-operative imaging technique in detecting ovarian tumor nature and spread. Sixteen patients that received 500-1000 microCi of I131 labelled HMFG2 mabs were evaluated. The scans obtained were compared mainly with the macro and microscopic operative findings of the subsequent laparotomy. Immunoscintigraphy accurately scanned tumor spread in 7 out of 9 patients with known ovarian cancer. It also successfully revealed the malignant or benign nature of pelvic masses in 6 out of 7 patients examined.

Adult↗
PubMedDate not supplied

Breast cancer imaging with radiolabelled peptide from complementarity-determining region of antitumour antibody.

Specific tumour imaging with radiolabelled monoclonal antibodies has been extensively investigated. Although some success has been reported, there are many limitations due to the slow kinetics, poor extravasation, catabolism by the reticuloendothelial system, and non-specific uptake of macromolecules such as antibodies. We have tried to overcome some of the problems associated with monoclonal antibodies while retaining their specificity by using an antibody-derived synthetic peptide. A synthetic pentadecapeptide (alpha M2) derived from the third heavy-chain complementarity-determining region (CDR-3H) of a tumour-associated monoclonal antibody was produced and shown to retain its specificity against the pan-carcinoma cell-surface antigen, polymorphic epithelial mucin, detected by the parent antibody. The peptide was radiolabelled with technetium-99m and injected intravenously to image malignant lesions in 26 women with primary, recurrent, or metastatic breast cancer. Visualisation of breast tumours and their metastases was obtained shortly after administration of alpha M2, and was optimum by 3 h. Overall, 57 (77%) of 74 sites were visualised. Successful imaging was achieved in 14 of 15 primary tumour sites and all of eight local recurrences. Five of six metastases in the opposite breast, eight of 15 metastatic axillary lymph nodes, and all of six metastatic supraclavicular lymph nodes were imaged. Metastatic sites in the lungs, mediastinum, chest wall, and liver were poorly visualised because of background cardiac blood pool. alpha M2 detected small lesions ( < 2 cm) as efficiently as larger ones. The peptide was rapidly (3 h) cleared from the circulation. No acute or chronic adverse reactions due to the alpha M2 were observed. Specific tumour targeting with the radiolabelled anticancer peptide alpha M2 offers new opportunities for breast cancer imaging and possibly therapy.

Adult↗
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↗