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Biomedical subjects

G Fountzilas

Publications and source records attributed to G Fountzilas.

At least 109 records · Page 6Linked to original sources

Intensified carboplatin regimen with GM-CSF support in non-small cell lung cancer (NSCLC). A Hellenic Co-operative Oncology Group Study (HeCOG).

This is a continuation of a HeCOG previous trial utilizing carboplatin and vindesine in conventional doses as a non-toxic regimen provided easily on an outpatient basis in NSCLC. In the present study we investigated whether an intensified dose-carboplatin could yield a better response. Carboplatin at a dose of 450 mg/m2 dose in combination with vindesine 3 mg/m2 every three weeks and GM-CSF support was used in a phase II study to treat 44 patients with non-small cell lung cancer (NSCLC). As compared to our previous study carboplatin dose intensity was increased from 75 mg/m2/wk to 150 mg/m2/wk. Six patients (13.6%) responded to treatment and all were partial responders. The median duration of response was 5 months (range 1.5-9 month). After a retrospective analysis a dose response effect was not evident at different carboplatin AUC doses. Twenty patients (45.45%) experienced thrombocytopenia and seventeen patients (38.6%) anemia as major toxicities. This study shows that in NSCLC a dose-response effect does not exist between carboplatin dose intensification and response rate cannot be traced.

Adult↗

Paclitaxel (175 mg/m2) plus carboplatin versus paclitaxel (225 mg/m2) plus carboplatin in non-small cell lung cancer: a randomized study.

A recent phase II study by our group documented a response rate of 27% with the combination paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 plus carboplatin dosed to a target area under the concentration-time curve of 7 in patients with advanced non-small cell lung cancer. In an effort to evaluate the dose-response relationship of paclitaxel with quality of life, we initiated a phase III prospective trial. Patients with inoperable non-small cell lung cancer were randomized into two groups. Group A received paclitaxel 175 mg/m2 plus carboplatin dosed to an area under the concentration-time curve of 6 every 3 weeks. Group B received the same regimen, with paclitaxel increased to 225 mg/m2. Since July 1996, 49 patients have entered the study, 29 in group A and 20 in group B. Patient and tumor characteristics were well distributed between both groups. In group A, 16 patients were evaluable, with one complete response, six partial responses, three stable disease, and six progressive disease. In group B, 12 patients were evaluable, with two partial responses, four stable disease, and six progressive disease. Treatment was well tolerated in both groups. More neurotoxicity and neutropenia were noticed with high-dose paclitaxel. There were no drug-related deaths. It is too early to draw definite conclusions regarding response and survival, but regarding toxicity, it seems that paclitaxel 225 mg/m2 plus carboplatin dosed to an area under the concentration-time curve of 6 is well tolerated without the use of growth factors. Although the results are premature, quality of life does not seem to be affected by the increased paclitaxel dose.

Adult↗

Paclitaxel with carboplatin versus paclitaxel with carboplatin alternating with cisplatin as first-line chemotherapy in advanced epithelial ovarian cancer: preliminary results of a Hellenic Cooperative Oncology Group study.

Ninety previously untreated patients with advanced epithelial ovarian cancer (International Federation of Gynecology and Obstetrics stages IIC, III, and IV) were randomized, after initial cytoreductive surgery, to receive paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 as a 3-hour infusion with either carboplatin at an area under the concentration-time curve of 7 (group A) or carboplatin at an area under the concentration-time curve of 7 on courses 1, 3, and 5, alternating with cisplatin 75 mg/m2 on courses 2, 4, and 6 (group B). Treatment was given every 3 weeks, up to a total of six courses. Sixty-one patients (33 and 28 patients in groups A and B, respectively) had residual disease after the initial cytoreductive surgery. Patients with measurable or evaluable disease had a high overall response (82% v 57%). A 52% and 39% complete response rate for groups A and B, respectively, with no statistically significant difference between the groups was also observed. With a median follow-up of 12 months (range, 0.33 to 24 months), 29 patients have progressed (18 and 11 in groups A and B, respectively), and 13 have died (seven and six, respectively). Median time to progression was 20.36 months (range, 0.20 to 23.54 months) for group A, whereas this has not yet been reached for group B. Median survival has not yet been reached, but there is no significant difference between the two groups (P = .6972). Treatment was generally well tolerated. Grade 3 and 4 neutropenia was 20% and 32% for groups A and B, respectively, while grade 3 and 4 thrombocytopenia was 4% and 7%, respectively, with no significant difference between the two groups. In conclusion, both combinations seem very active for the treatment of advanced epithelial ovarian cancer and are associated with acceptable toxicity.

Adult↗

Paclitaxel in combination with carboplatin or gemcitabine for the treatment of advanced head and neck cancer.

We performed a phase II study to evaluate the activity and toxicity of the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin as first-line treatment in patients with recurrent or metastatic head and neck cancer. From March 1994 until August 1996, 49 patients were treated with paclitaxel 200 mg/m2 by 3-hour infusion followed by carboplatin at an area under the concentration-time curve of 7 mg/mL x min; treatment was requested every 4 weeks. Granulocyte colony-stimulating factor was administered prophylactically on days 2 to 12 of each cycle. The study included 41 men and eight women, with a median age of 57 years (range, 23 to 73 years). Most of the patients were symptomatic and had locoregional disease. Primary sites included nasopharynx (14 patients), oropharynx (six), oral cavity (four), hypopharynx (three), larynx (20), paranasal sinuses (one), and unknown (one). After the completion of treatment, four patients (8%; 95% confidence interval, 0% to 16%) achieved a complete response and 12 (24%; 95% confidence interval, 12% to 37%) achieved a partial response. Grade 3/4 toxicities included anemia (2%) and leukopenia, thrombocytopenia, nausea/vomiting, diarrhea, and stomatitis (4% each). After a median follow-up of 15.3 months, median time to progression was 5.7 months (range, 0.5 to 29.8+ months) and median survival was 13.3 months (range, 0.5 to 30.2+ months). In our ongoing study in a similar patient population, gemcitabine was substituted for carboplatin.

Adult↗

Prognostic variable in patients with advanced colorectal cancer treated with fluorouracil and leucovorin-based chemotherapy.

Possible prognostic variables for tumor response, time to progression (TTP), and survival in 141 patients with advanced colorectal cancer treated with fluorouracil and leucovorin-based chemotherapy were analyzed. None of the variables examined for their possible influence on tumor response attained significance in the stepwise logistic regression. In the univariate analysis, variables found to be strongly associated with TTP were performance status (PS) (P = 0.0301), liver involvement (P = 0.030), and the initial values of WBC (P = 0.0319), lactic dehydrogenase (LDH; P = 0.0053), gamma-glutamyl-transpeptidase (gamma-GT; P = 0.0013), alkaline phosphatase (ALP; P = 0.0186), albumin (P = 0.0004), and carcinoembryonic antigen (CEA; P = 0.0014). In the Cox analysis, liver involvement (P = 0.0553), albumin (P = 0.0181), PS (P = 0.484), and ALP (P = 0.0553) were retained as independently significant variables. When only patients with liver metastases were included in the analysis, then only albumin (P < 0.001) demonstrated a prognostic significance. Also, in the univariate analysis, variables predicting survival were PS (P = 0.0230), grade (P = 0.00600), liver involvement (P = 0.0002), LDH (P = 0.0001), gamma-GT (P < 0.001), ALP (P = 0.0006), albumin (P = 0.0309), and CEA (P = 0.005). With the multivariate analysis, gamma-GT (P = 0.0004), albumin (P = 0.0634), and CEA (P = 0.0804) were selected as significant. In those patients who presented with liver involvement, variables predicted survival were gamma-GT (P = 0.0041), albumin (P = 0.0442), and the percentage of involved liver parenchyma (P = 0.0690). These results could be helpful for the stratification of future trials in advanced colorectal cancer.

Adult↗

Widespread Castleman disease: CT findings.

The widespread form of Castleman disease is a rare condition with aggressive, often fatal course. We describe the imaging findings of two patients with extensive Castleman lymphadenopathy. The duration of the disease was 8 years in one patient and 4.5 months in the other.

Castleman Disease↗

A phase II study of paclitaxel in advanced breast cancer resistant to anthracyclines.

33 women with advanced breast cancer resistant to anthracyclines were treated with paclitaxel 175 mg/m2 in a 3 h infusion every 3 weeks. The median age was 53 years (range 30-72) and the median performance status was 1 (range 0-2). 24 (73%) patients had visceral metastases while 22 (67%) had > or = two involved sites. 23 (70%) patients received anthracycline or mitoxantrone in an adjuvant setting and 21 (64%) for advanced disease. There were two (6%, 95% confidence interval (CI) 1-20%) complete responses (CRs) and 12 (36%, 95% CI 20-55%) partial responses (PRs). Median dose intensity of paclitaxel delivered was 58 mg/m2/week. Median time to progression was 24 weeks (range 4-61) and median survival was 41 weeks (range 8-66). Grade 3-4 toxicities included leucopenia (9%), stomatitis (3%), alopecia (91%), neurotoxicity (9%), infection (3%) and diarrhoea (3%). In conclusion, paclitaxel at a dose of 175 mg/m2 exhibits significant activity in advanced breast cancer resistant to anthracyclines.

Adult↗

Carboplatin alone compared with its combination with epirubicin and cyclophosphamide in untreated advanced epithelial ovarian cancer: a Hellenic co-operative oncology group study.

We compared, in a multicentric randomised prospective study, the efficacy and toxicity of carboplatin 400 mg/m2 as a single agent (CB) to a combination of carboplatin 300 mg/m2, epirubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (CB-EC) in advanced ovarian cancer patients. The treatment was scheduled to be administered every 3 weeks for six courses. Following initial laparotomy and cytoreductive surgery, 130 previously untreated patients entered the study. 73 patients were treated with carboplatin alone while 57 received the combination chemotherapy. In the majority of the patients, the regimens had to be given every 4 weeks due to myelosuppression. Nausea, vomiting and alopecia were more severe in the CB-EC arm. Overall, clinical complete response was observed in 73 (56%) and partial response in 20 (15%) patients. The median time to progression was 16.89 months and median survival was 29.54 months. No significant differences in response rate, time to progression, disease-free survival and overall survival were observed between the two treatment arms. The prognostic role of residual disease after initial surgery, complete remission at second-look laparotomy, tumour stage and performance status was confirmed.

Adult↗

Treatment of unresectable recurrent head and neck carcinoma with 13-cis-retinoic acid and interferon-alpha. A phase II study.

Sixteen patients with unresectable recurrent head and neck carcinomas were treated with 13-cis-retinoic acid and interferon-alpha. All patients had presented with recurrences after having been treated primarily with surgery and radiotherapy, while two of them had also received induction chemotherapy. The site of relapse was strictly locoregional in all cases (only at the primary site in three cases, at the cervical lymph nodes only in four cases and both at the primary site and the neck in the remaining nine cases. Two patients were female, and 14 male, with an age range of 47-72 years (median 61 years). Interferon-alpha was administered subcutaneously at a dose of 3 x 10(6) IU every second day. The dose of retinoids was 40 mg per os every day. The duration of treatment was two to 14 months (median seven months). There were two cases of partial response (tumour regression > 50 per cent), eight cases of stable disease lasting for three to seven months (median four months) and six cases presented with progressive disease. All patients died after a survival of three to 17 months (median 9.5 months). Toxicity was generally minimal. We believe that the results are not encouraging, but also not disappointing. The fact that toxicity was indeed mild, with not a single case of life-threatening sequellae even after prolonged administration of the two agents, allows us to conclude that an increase of the dose of IFN-alpha might be more beneficial. Selection of patients with more 'favourable' recurrences will give a better chance to the treatment combination to prove its real efficacy. Larger numbers of patients have to be treated and evaluated before definite conclusions can be reached.

Aged↗

Prolonged intraperitoneal infusion of 5-fluorouracil using a novel carrier solution.

A novel peritoneal carrier solution, Icodextrin 20 (7.5%), has allowed exploration of prolonged, intraperitoneal (i.p.) infusion of the cytotoxic drug 5-fluorouracil (5-FU). A phase I and pharmacokinetic study was performed to determine the toxicities and maximum tolerated dose of prolonged and continuous intraperitoneal 5-FU in patients with peritoneal carcinomatosis. Seventeen patients were entered into this study. Each patient had a Tenckhoff catheter placed into the peritoneal cavity under general anaesthetic. After initial flushing and gradual increase in exchange volumes with Icodextrin 20, 5-FU was administered daily from Monday to Friday, 50% as a bolus in the exchange bag and 50% in an elastomeric infusor device delivering continuous 5-FU to the peritoneal cavity at 2 ml h-1. Treatment was continued for 12 weeks or until intolerable toxicity developed. Abdominal pain and infective peritonitis proved to be the main dose-limiting toxicities. Initial problems with infective peritonitis were overcome by redesign of the delivery system, and it proved possible to deliver 300 mg m-2 5-FU daily (5 days per week) for 12 weeks. Pharmacokinetic studies showed i.p. steady-state 5-FU concentrations (mean 47 500 ng ml-1) that were > 1000-fold higher than systemic venous levels (mean 30 ng ml-1).

Adult↗

A prospective randomized phase III study in non-small-cell lung cancer comparing cisplatin, ifosfamide, vinblastine (VIP) versus cisplatin, ifosfamide and etoposide (VIP-16). Hellenic Co-Operative Oncology Group.

BACKGROUND: It was recently reported that when ifosfamide was added to cisplatin and vinblastine the response rate was increased but not the survival in patients with non-small-cell lung cancer (NSCLC). The purpose of this study was to investigate the possibility of increased responses and survival with use of the combination of cisplatin, ifosfamide, etoposide (VIP-16) in comparison to the combination of cisplatin, ifosfamide, vinblastine (VIP) in non-operable NSCLC. PATIENTS AND METHODS: Two hundred twelve patients with histologically confirmed diagnoses of NSCLC were randomized into two groups: group A received cisplatin 100 mg/ m2, vinblastine 6 mg/m2 and ifosfamide 3 mg/m2 i.v. on day 1 every 3 weeks; group B received the same regimen except that etoposide 120 mg/m2 was substituted for vinblastine on days 1, 2, and 3. Patients were well balanced for age, sex, performance status (PS), stage, grade, histology and sites of disease, and the relative dose intensity was similar in both groups. RESULTS: One hundred one patients were evaluable for response in group A and 99 in group B. The overall response rates were 29% in group A (5CR) and 25% in group B (3CR). The median time to progression was 7.51 (2-35) months for group A and 7.7(1-28) months for group B (P = 0.34). The median survival was 8.49 (0.33-37.44) months for group A and 9.38 (0.43-36.59) for group B (P = 0.39). Multivariate Cox stepwise analysis showed stage to be the only significant prognostic factor for survival (P = 0.0114). Toxicity was not remarkable and not different between the two groups except for alopecia which was much more common in the patients who received etoposide. CONCLUSION: VIP and VIP-16 combination chemotherapies are equally active in NSCLC with acceptable toxicity. Stage proved to be the most significant prognostic factor for survival in this study.

Adult↗

Recombinant interferon ALFA-2A in combination with carboplatin, vinblastine, and bleomycin in the treatment of advanced malignant melanoma.

Thirty-four patients with advanced malignant melanoma were treated with recombinant alpha-interferon (IFN) and chemotherapy consisting of carboplatin, vinblastine, and bleomycin (CVB). CVB was given for four cycles and IFN for 1 year or until progression. Of the 34 analyzed patients, 17 (50%) achieved an objective response, including two complete (6%) and 15 partial responses (44%). Responses were noted in cutaneous, lymph node, and pulmonary sites, with a median time to disease progression of 5 months (range, 3-20 months). The median survival from onset of therapy was 8 months (range, 1-22 months) for the 34 patients. Ninety-four percent of the patients experienced flu-like symptoms and 82% fatigue or weakness. Leukopenia grade 3-4 was observed in four patients (12%). There were two toxicity-related deaths (6%); one from bleomycin-induced pneumonitis and one from neutropenic sepsis. It is concluded that the addition of IFN to CVB regimen, in this study, showed no apparent advantage on response rates, disease-free interval, or survival. The observed treatment-related mortality was unacceptably high. IFN administered as maintenance therapy following CVB conferred no survival benefit.

Adult↗

Primary angiosarcoma of the brain: case report.

A 41-year-old patient with a primary angiosarcoma of the brain is reported. The tumor was located in the left parietal lobe and was radically removed. The diagnosis of angiosarcoma was established by immunohistochemistry. The patient was postoperatively treated with adjuvant chemotherapy and then radiation therapy. After 41 months, she was in excellent clinical and neurological condition without any sign of recurrence.

Adult↗

Intraventricular administration of morphine for control of intractable cancer pain in 90 patients.

OBJECTIVE: To quantitate the relief of intractable cancer pain by the use of intraventricular morphine administration. METHODS: Intraventricular morphine administration was performed through an Ommaya reservoir. An initial dose of 0.25 mg of morphine sulfate per 24 hours was administered to all of the patients. This dose was progressively increased in 0.25-mg increments until optimal analgesia was attained. RESULTS: Sixty men and 30 women with a median age of 58 years (range, 23-80 yr) entered the study. The median duration of pain was 6 months (range, 0.5-120 mo). A daily morphine dose of up to 1 mg was adequate to achieve an analgesic effect in 77% of the patients. Only nine patients (10%) achieved < 50% pain relief. Using a multiple regression analysis, only the morphine dosage was found to be an independent prognostic factor. The most frequent side effect (22%) was nausea/vomiting. Also, there were two patients with opioid intolerance and two with intracerebral hematomas. Three reservoirs failed. CONCLUSION: Intraventricular morphine administration is a useful method for palliation of intractable cancer pain.

Adult↗

Fluorouracil and leucovorin with or without interferon alfa-2b in advanced colorectal cancer: analysis of a prospective randomized phase III trial. Hellenic Cooperative Oncology Group.

PURPOSE: To investigate if double modulation of fluorouracil (5-FU) with leucovorin (folinic acid [FA]) and interferon alfa-2b (IFN 2b) improves responses and survival in comparison to single modulation of 5-FU with FA. PATIENTS AND METHODS: One hundred six patients with histologically confirmed advanced colorectal cancer, measurable disease, and without previous chemotherapy were prospectively randomized into two groups. Patients in group A received 5-FU 450 mg/m2 as an intravenous bolus in the midinfusion of FA weekly. FA was given at a dose of 200 mg/m2 in 500 mL 0.9% normal saline solution in 2-hour infusion. Patients in group B received exactly the same regimen plus IFN 2b 5 million units subcutaneously three times weekly. RESULTS: All patients were well balanced in both groups regarding age, sex, performance status, number, and site of metastasis. One hundred two patients were assessable. All patients have died. There was no difference in response between the two groups (7.8% v 9.8%). Median survival was 10.1 months in group A, and 7.2 months in group B (P = .00189). Median time to progression was 8.4 and 5.2 months, respectively (P = .00196). Overall, better performance status and older age had a positive impact on survival. Toxicity was the most important and catastrophic aspect of this study. Patients who received IFN 2b had significantly worse anemia, neutropenia, diarrhea, anorexia, weight loss, flu-like syndrome, and psychological reactions. CONCLUSION: Based on this final analysis, the addition of IFN 2b to the combination of 5-FU and FA enhances toxicity and contributes to decreased survival.

Adult↗

Cisplatin and continuous infusion of fluorouracil followed by radiation and weekly carboplatin in the treatment of locally advanced head and neck cancer: a Hellenic Cooperative Oncology Group study.

Induction chemotherapy followed by radiation has been extensively studied in an effort to improve local control and possibly overall survival of patients with locally advanced head and neck cancer. From June 1989 until May 1991, 39 patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with 3 cycles of induction chemotherapy, consisting of cisplatin (100 mg/m2 d 1) and fluorouracil (1000 mg/m2 d 2-6) followed by radiation potentiated by weekly administration of carboplatin (60 mg/m2). Surgery was performed in selected patients with residual disease after the combined modality approach. Four cycles of adjuvant chemotherapy with carboplatin (325 mg/m2) and bleomycin (15 u) were administered in those patients who demonstrated a partial response after locoregional treatment. There were 36 men and 3 women with a median age of 56 (range 39-74) years and Karnofsky performance status of 70 (range 60-100). The primary site of the tumor was nasopharynx (8), oropharynx (8), hypopharynx (3), oral cavity (4), larynx (13), paranasal sinus (2), and salivary glands (1). Thirty-two (82%) patients presented with stage IV disease. After the completion of induction chemotherapy, 14 (36%, 95% CI 21-53%) patients achieved a complete response (CR). This CR rate was increased to 56% (95% CI, 42-74%) after locoregional treatment. Main toxicities included nausea/vomiting (56%), leukopenia (40%), anemia (30%), thrombocytopenia (10%), stomatitis (28%), diarrhea (17%), and alopecia (12%). Median relapse-free survival was 18 (1-50) months, median time to progression was 13 (0.3-58.5) months, and median survival 19 (0.3-59) months. Induction chemotherapy with cisplatin and fluorouracil followed by radiation potentiated with carboplatin is feasible. However, this combined modality approach, as applied in the present study, does not appear to yield superior results than those reported with chemotherapy followed by radiation alone.

Animals↗

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

Based on the high activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in non-small cell lung cancer (NSCLC) and the superior 1-year survival rates of patients with NSCLC treated with carboplatin, the Hellenic Cooperative Oncology Group initiated a phase II trial to investigate the efficacy and toxicity of the combination of both agents in patients with nonoperable stage III and IV NSCLC. Since July 1995, 31 eligible patients have entered into this study. All patients received paclitaxel 175 mg/m2 as a 3-hour infusion plus 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 (range, 29 to 73 years) and the median performance status was I (range, 0 to 2). Most of the patients had stage IV adenocarcinoma (19 patients), with poor differentiation (15 patients). The median number of prior chemotherapy cycles was two, with a range of one to six. Among 21 evaluable patients, seven achieved a partial response, 10 had stable disease, and four had progressive disease. It is too early for evaluation in nine patients. Grade 2/3 nonhematologic toxicities included alopecia (46.4%), neurotoxicity (3.3%), and myalgia/arthralgia (7.1%). Grade 2/3 neutropenia was experienced by 10.7% of patients, whereas grade 2 thrombocytopenia was seen in only 3.3%. One patient died following complications of severe allergic reaction. In conclusion, although this study is ongoing, it is clear that the combination of paclitaxel and carboplatin is effective and well tolerated in patients with nonoperable NSCLC.

Adult↗

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↗