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Biomedical subjects

G Fountzilas

Publications and source records attributed to G Fountzilas.

At least 127 records · Page 7Linked to original sources

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↗

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↗

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↗

Retinoids in the management of head and neck cancer. An update.

Despite smoking cessation programs and recent advances in cancer treatment, it is anticipated that head and neck cancer along with lung and esophageal cancers will still be a serious health hazard worldwide. Cancer chemoprevention represents a promising new area of intensive clinical research. Chemoprevention agents which have been considered in clinical trials with the intention of reversing the carcinogenic process include natural agents as well as synthetic retinoids. At the molecular level these agents seem to modify gene expression through the mediation of intracellular-binding proteins and nuclear receptors. In vitro, retinoids induce tumor cell differentiation, inhibit proliferation and also affect other important cell functions, such as adhesion and invasion. Clinical studies conducted in individuals with premalignant lesions, such as oral leukoplakia or laryngeal papillomatosis, have shown that retinoids have the capability to reverse the malignant process in the majority of cases. Furthermore, in patients with head and neck tumors, who became disease-free, after primary treatment, 13-cis retinoic acid (isotretinoin) significantly reduced the incidence of second primaries as compared to placebo. These exciting results urged investigators in Europe and the USA to organize confirmatory trials as well as other chemoprevention trials in order to evaluate the role of new agents. It is hoped that these trials will clarify several important aspects of chemoprevention, such as the safety and activity of new compounds, the significance of integration of retinoids with chemotherapy and/or biotherapy and the establishment of biological markers as intermediate endpoints of carcinogenesis.

Animals↗

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↗

Randomised trial of epirubicin versus fluorouracil in advanced gastric cancer. An International Collaborative Cancer Group (ICCG) study.

BACKGROUND: It is not yet established whether doses of epirubicin equitoxic to adriamycin are more effective in the treatment of locally advanced or metastatic gastric cancer. PATIENTS AND METHODS: Seventy patients with advanced gastric cancer were randomised to receive fluorouracil (500 mg/m2 days 1-5 every three weeks) or epirubicin (100 mg/m2 every three weeks), with doses escalating to a maximum dose of 700 mg/m2 of fluorouracil or 140 mg/m2 of epirubicin. RESULTS: No patients attained complete response. Partial response was seen in 3 patients in the epirubicin arm (8%) compared with 2 patients in the fluorouracil arm (6%). No statistically significant difference between the two treatments was seen in either response or survival. Severe side effects, particularly alopecia, and nausea and vomiting were more common in the epirubicin arm (45% and 37%, respectively) compared with the fluorouracil arm (12% and 8%, respectively). CONCLUSIONS: Our trial demonstrates that fluorouracil and epirubicin as single agents have comparable but insufficient activity in advanced gastric cancer.

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↗

Extragonadal choriocarcinoma in a patient with Down syndrome.

There are several reports suggesting that there is a higher incidence of leukemia and testicular cancer in patients with Down syndrome. Fifteen patients with Down syndrome and testicular cancer were previously reported. The median age at diagnosis of testicular cancer was 18 years, (range: 3-45). The histologic subtypes were seminoma in 9 patients, not specified in 2 patients, and 1 patient each of adenocarcinoma, yolk sac, embryonal, and teratocarcinoma. In this article we describe a case of extragonadal choriocarcinoma in a patient with Down syndrome. To our knowledge, this is the first case ever reported. The patient had a complete remission following chemotherapy with cisplatin, etoposide, and bleomycin and is disease-free with a follow-up of 32 months. Patients with Down syndrome and advanced testicular cancer should be treated with potentially curative chemotherapy.

Abdominal Neoplasms↗

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↗

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↗

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↗

A phase II trial of carboplatin and vindesine in patients with non-small cell lung cancer. A Hellenic Cooperative Oncology Group study.

In an effort to investigate a regimen less toxic and more convenient than cisplatin combinations, 50 patients with non-small cell lung cancer (NSCLC) were treated in a Phase II study with carboplatin and vindesine. Carboplatin 300 mg/m2 every 28 days and vindesine 3 mg/m2 every 2 weeks were administered on an outpatient basis. Eight patients had a partial response of their disease (16%, confidence limits 7-29%). Mean duration of response was 4.5+ months (1 +/- 8). Toxicity, mainly of grade I-II, was noticed in 4-28% of the patients. The most common side effect was mild to moderate leukopenia (28%). The combination of carboplatin and vindesine at the above doses was very well tolerated. Although the response rate was relatively low, the survival in this patient population was similar to other cisplatin-containing regimens.

Aged↗

Supraglottic laryngectomy: experience with 66 patients over 20 years.

We reviewed the records of 66 consecutive patients with previously untreated supraglottic laryngeal carcinoma who underwent a supraglottic laryngectomy in our department between 1970 and 1989. There were 23 T1, 30 T2 and 13 T3 cases. Eight patients had neck metastases and underwent neck dissection also. Twenty-four (36 per cent) patients received post-operative radiotherapy. Two-year and five-year survival rates were 88.9 per cent and 82.2 per cent respectively. When the survival rates of the patients with T1, T2 and T3 lesions were calculated separately and compared with each other the differences were not statistically significant. Recurrences, post-operative complications, time to progression and indications for supraglottic laryngectomy are discussed.

Adult↗

The role of interferons in the treatment of colorectal cancer.

There is a substantial body of evidence suggesting in vivo synergy between fluorouracil (FU) and interferons (IFNs). The mechanism(s) which is implicated in the expression of synergy with the combination of FU and IFNs is unknown. Although phase I studies have demonstrated a pharmacokinetic advantage for this combination, subsequent phase II studies in patients with advanced colorectal cancer showed that only one-third of the patients responded partially to this treatment. Double modulation of FU with leucovorin and IFN does not appear to add any survival benefit to these patients compared to single modulation of FU by IFN. In conclusion, the role of IFNs in the treatment of colorectal cancer has not been defined yet. It is hoped that phase III trials which currently are in progress will clarify this issue.

Antineoplastic Combined Chemotherapy Protocols↗

Megestrol acetate in cancer patients with anorexia and weight loss. A Hellenic Co-operative Oncology Group (HeCOG) study.

Fifty-two patients with hormone-independent cancer, who complained of anorexia and of weight loss with at least 10%, received megestrol acetate (MA), 480 mg daily, during 1-21 weeks. Of the 41 patients treated during 4 weeks or longer, 38 experienced weight gain. Monthly subjective evaluation of six parameters using a linear analog self-assessment (LASA) form showed a significant improvement in the patient's rating of appetite, mood, nausea and vomiting, and quality of life; the tumor was progressive in 21, stable in 11 and it regressed in only 9 of these patients. No toxicity was observed; one case of death due to a congestive heart failure remains unexplained. MA at the dose used is a powerful appetite stimulant; it contributes to weight increase and might improve the subjective appreciation of quality of life. MA at lower doses should be compared in a prospective trial to the dose used in this study.

Adult↗

Vertical partial laryngectomy: our results after treating 81 cases of T2 and T3 laryngeal carcinomas.

From 1976 to 1989, 81 patients with T2 and T3 laryngeal carcinomas were treated with vertical patrial laryngectomy at the University ENT Department of Thessaloniki, Greece. All patients were male with a median age of 56 years (33-71 years). Four patients had N1 lymph nodes. Ten patients received post-operative radiotherapy. Seventeen patients developed local recurrences or distant metastases. Mean follow-up was more than seven years. Absolute three-year survival was 94.6 per cent for 74 patients and absolute five-year survival was 89.6 per cent for 58 patients. Actuarial five-year survival of the whole group of 81 patients was 91 per cent calculated with the Kaplan-Meier method. Recurrence rate and survival of stage II and III patients are also discussed and compared using the log-rank test. We conclude that vertical partial laryngectomy is a very successful treatment selection for T2 glottic and false vocal cord carcinomas and for some selected T3 glottic lesions.

Adult↗

Factors influencing complete response and survival in patients with head and neck cancer treated with platinum-based induction chemotherapy. A Hellenic Co-operative Oncology Group Study.

One hundred fifteen consecutive patients with locally advanced carcinoma of the head and neck were treated between August 1984 and August 1989 with three cycles of either of two platinum-based induction chemotherapies, followed by local treatment. After the completion of chemotherapy 26 (23%) patients had complete responses (CR). Several pre-treatment characteristics were analyzed for a possible correlation to CR to induction chemotherapy and to survival. The following variables were closely interrelated: sex, history of smoking, alcohol abuse, histologic type, tumor site and grade. Tumor stage and negative history of smoking were correlated with CR. The variables which were individually correlated with survival were keratinization, CR to chemotherapy, alcohol abuse, histologic type, site and grade of the primary tumor, serum albumin level and tumor stage. A regression analysis after Cox's model to identify a limited set of predictors selected CR, serum albumin, tumor grade, performance status and nodal status as the most significant; when analyzing the data without the time-dependent variable CR, the factors selected by the model were serum albumin, tumor grade, performance status and tumor stage. In conclusion, serum albumin level, tumor grade, performance status and tumor stage prior to treatment can be used to define risk classes in our patient population.

Adolescent↗

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↗