Biomedical subjects

P Kosmidis

Publications and source records attributed to P Kosmidis.

At least 73 records · Page 4Linked to original sources

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1996

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

In the present study we evaluated the response rate and the immunorestorative properties of interferon alpha 2b (IFn alpha 2b) administered to patients with advanced renal cell carcinoma (RCC), melanoma (MEL) or colorectal cancer (CC). We studied the immune status and correlated it with clinical responses. Thirty-five patients with advanced RCC, and 14 with MEL were treated with recombinant INF alpha 2b. The dose was increased progressively from 5 x 10(6) IU/day in the first week (three times every week) to 10 x 10(6) IU/day in the second week and thereafter to 15 x 10(6) IU/day subcutaneously. In patients with CC INF alpha 2b was given at 5 x 10(6) IU/day every other day (three times every week); these patients also received (together with INF) leucovorin 200 mg m-2 day-1 in a 1-h i.v. infusion every week, and mid-infusion 400 mg/m2 5-FU was administered as an intravenous bolus every week. The response rate was as follows: for RCC, 6 patients achieved partial response (PR), 10 stable disease (SD), and 21 progressed (PD); for MEL, 5 patients achieved PR and 9 PD; for CC, 6 achieved PR, 5 SD, and 9 PD. In all patients blood was withdrawn prior to INF alpha 2b treatment and then monthly. T lymphocytes, after isolation from peripheral blood, were tested for proliferation in the autologous mixed-lymphocyte reaction and allogeneic mixed-lymphocyte reaction, interleukin-2 (IL-2) production, expression of IL-2 receptors during the allogeneic-mixed-lymphocyte reaction, and the production of IL-1 by peripheral blood monocytes. Striking increases were demonstrated in all parameters 2 months after treatment with INF alpha 2b. In comparison to normal controls, all patients with the malignant neoplasms presented decreased (> 45%) mean values of the immunological parameters under investigation (P 0.0001). Responders (patients with RCC, MEL, and PR) presented lower mean values of all the parameters studied than did non-responders (P 0.0001). Patients with CC presented the lowest mean values of the parameters than did the other patients (RCC, MEL) (P 0.0001). After therapy with INF alpha 2b, patients with RCC experiencing PR showed a mean increase of more than 30% (P 0.0001). Patients with SD showed a mean increase of about 20% (P 0.0001), and those with PD showed a 6% increase in the immunological parameters under investigation. Patients with MEL experiencing PR showed a mean increase of more than 30% and patients with PD a decrease of more than 10% (P 0.0001). All patients, regardless of the clinical response, achieved an increase of more than 60% (P 0.0001). Administration of IFN alpha 2b resulted in a marked potentiation of a deficient cellular immune response in vitro in those patients with RCC and MEL who responded to the treatment. On the other hand, non-responders demonstrated a decrease in the examined parameters and, in some, deterioration of the already depressed immunological functions was observed. This observation can have prognostic significance regarding clinical response of INF. In contrast, our findings show that the immune stimulation associated with INF alpha treatment in all our CC patients did not predict an improved clinical outcome. There are several theoretical explanations for this discrepancy.

Adult↗

PubMed1996

Biochemical modulation of fluorouracil: comparison of methotrexate, folinic acid, and fluorouracil versus folinic acid and fluorouracil in advanced colorectal cancer: a randomized trial.

Recent advances in biochemical pharmacology have revealed the basis for the biological modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and folinic acid (FA). Sequential use of MTX given 24 h prior to 5-FU has resulted in enhanced cell kill in vitro and in vivo. In addition, administration of FA prior to 5-FU has led to potentiation of 5-FU action by stabilization of the ternary complex of thymidine synthase. In the present randomized study, two groups of patients with advanced colorectal cancer were treated as follows: 43 patients (pts) in group A received 5-FU + FA, whereas 45 pts in group B received 5-FU + FA + MTX. The dosage was as follows: group A received FA i.v. at 300 mg/m2 per day, prior to i.v. 5-FU at 500 mg/m2 per day on days 1-4; group B was given MTX i.v. at 130 mg/m2 per day on day 0, followed 24 h later by FA at 15 mg q6h x 6, and 5-FU + FA was started on day 1 and given at the same doses and schedule described for group A. Objective responses were achieved by 8/43 pts in group A (1 complete response and 7 partial responses) and by 18/45 pts in group B (3 complete and 15 partial responses), all occurring in the liver. There was no significant difference in the median time to progression (group A 6.1 months, group B 6.8 months) or the median survival (group A 9.2 months, group B 10.3 months). Toxicity was significantly greater in group B [grade 2-3 mucositis 20% versus only 2% in group A (P < 0.0001); grade 3 diarrhea in group B 15% versus 3% in group A (P < 0.001)]. According to our results, double biological modulation of 5-FU with MTX + FA led to an enhanced response rate with increased toxicity as compared with the 5-FU + FA regimen given at less than its maximally tolerated dose.

Adenocarcinoma↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1996

TPA, TATI, CEA, AFP, beta-HCG, PSA, SCC, and CA 19-9 for monitoring transitional cell carcinoma of the bladder.

A total of 76 patients with transitional cell carcinoma of the bladder were prospectively monitored with simultaneous serum value estimations of tumor polypeptide antigen (TPA), tumor-associated trypsin inhibitor (TATI), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (beta-HCG), prostatic specific antigen (PSA), squamous cell carcinoma antigen (SCC), and CA 19-9 in different stages and phases of their disease. In locally advanced disease positive values were noted for TATI in 22/28 patients (78.5%), for TPA in 17/28 (60.7%), for CA 19-9 in 10/28 (35.7%), for CEA 11/28 (39.2%), for beta-HCG in 3/28 (10.7%), for PSA in 6/28 (21.4%), for SCC in 6/28 (21.4%), and for AFP in 0/28. In metastatic disease elevated levels were observed for TATI in 43/48 patients (89.5%), for TPA in 41/48 (85.4%), for CA 19-9 in 19/48 (39.5%), for CEA in 20/48 (41.6%), for beta-HCG in 6/48 (12.5%), for PSA in 7/48 (14.5%), for SCC in 8/48 (16.6%), and for AFP in 1/48 (2.1%). In metastatic disease TATI and TPA values were significantly modified in patients with complete remission and TATI, TPA, and CA 19-9 in patients with partial remission and nonresponders. In T2-T4-N0M0 tumors, TPA, TATI, CA 19-9, and CEA were significantly increased in nonresponders. In patients with complete remission, a change in serum TATI, TPA, and CA 19-9 levels cannot be evidenced with the available numbers. The concurrent determination of TATI and TPA in T2-T4N0M0 tumors and TATI, TPA, and CA 19-9 in generalized disease could predict the response to chemotherapy. This study indicates that only the determination of TATI and TPA and in some degree the CA 19-9 is a potential tool for monitoring the efficacy of treatment.

Adult↗

PubMed1996

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↗

PubMed1996

5-Fluorouracil, epirubicin, and mitomycin C versus 5-fluorouracil, epirubicin, mitomycin C, and leucovorin in advanced gastric carcinoma. A randomized trial.

Leucovorin (LV) enhances the activity of 5-fluorouracil (5FU). Based on these data, we performed a randomized trial with 5FU, epirubicin (EPI), mitomycin C(MMC) with/ without LV in advanced gastric cancer (AGC). The purpose of our study was to investigate if the addition of LV improved the response rate of the combination 5FU EPI, MMC (FEM) over FEM. From January 1988 until April 1994, 88 patients with recurrent or metastatic AGC were randomly received 5FU, EPI, MMC with (group A) or without (group B) LV. Between the two arms of the study no difference was noticed in sex, performance status, primary site of tumor, and lymph node metastases. Therapy included group A (5FU 600 mg/m2/day, i.v. bolus, on days 1, 8, 29, 36, and EPI 45 mg/m2/day, i.v. bolus, on days 1 and 29, MMC 10 mg/m2/day, i.v. bolus, on day 1) and group B (the same as group A plus LV 200 mg/m2/day by 2 h intravenous infusion with 5FU intravenous push at midinfusion). No significant difference in response rate was noticed between the two treatment arms; there were two (5%) patients with complete response in group A, and five (12%) in A and 11 (26%) partial responders in group B (p < 0.1). A significantly higher number of patients achieving stable disease was observed in group B; 19 (44%) in comparison to group A 10 (24%) (p < 0.048). There were more patients with progressive disease in group A 25 (59%) than in group B 12 (28%) (p < 0.003) (Table 2). No difference was noted in mean duration of response: group A, 15.8 (6-31) weeks; and group B, 17.6 (6-28) weeks. The mean time to progression was for group A [11.4 (6-35) weeks] and for group B [17.6 (8-33) weeks]. Mean survival was for group A [27.4 (12-59) weeks] and for group B [30.6 (17-53) weeks], for 50% of patients. Causes of death were, for group A, 40 patients from disease progression and two sudden deaths; for group B, causes of death were for 41 patients disease progression and two sudden deaths. There were two patients in group A and one in group B that were not evaluable because they abandoned therapy after the first cycle. Toxicity was increased in group B; anemia, nausea and vomiting, and alopecia (p < 0.055) were more severe in group B, but not statistically different when compared to group A. Neutropenia, thrombocytopenia, mucositis, and fatigue of any grade were significantly more common and severe in group B. Significant dose reductions due to toxicity were required more commonly in group B. We conclude that the response rate was increased in the schedule with the addition of LV, at the cost of increased toxicity and with no difference in survival. A randomized trial comparing FEM-LV with new generation regimens would determine whether the addition of LV qualifies FAM equally active with these.

Adult↗

PubMed1996

Quality of life as a new end point.

Quality of life (QOL) is a relatively new clinical end point that is particularly relevant to the typically palliative therapy for non-small cell lung cancer. Patients' assessments of their QOL are shown to differ from their physicians', emphasizing the subjective nature of QOL. A number of relevant instruments and assessment techniques are employed. Results from a study using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 instrument before and during chemotherapy are presented. Some parameters improved while others did not, preventing a simple interpretation. There are arguments for compiling indexes of QOL while retaining measures for individual parameters and a desire for the consistent international use of an instrument such as the EORTC questionnaire.

Carcinoma, Non-Small-Cell Lung↗

PubMed1996

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↗

PubMed1996

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↗

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↗

PubMed1995

Analysis of interactions between the corneal epithelium and liposomes: qualitative and quantitative fluorescence studies of a corneal epithelial cell line.

Transcorneal drug transport is normally limited by the intrinsic permeation characteristics of the corneal epithelium. However, liposomes, i.e., phospholipid vesicles composed of phospholipid membranes, have recently attracted attention as carriers of topically applied agents. The present study therefore describes a qualitative and quantitative laboratory investigation of interactions between corneal epithelial cells and liposomes. The lipid bilayers and interior spaces of liposomes were labelled with different fluorophores. Fluorescence microscopy revealed a rapid uptake of rhodamine B-labelled liposome bilayer components by the epithelial cell membrane and the cytoplasm. Simultaneously, intracellular uptake of aqueous liposome content was indicated by uniform fluorescence of the cytoplasm due to carboxyfluorescein (CF). The fluorimetric experiments showed that the uptake of liposomes by SIRC cells depended on liposome concentrations and the time of exposure of the cells to the liposomes, and that saturation effect characteristics were present. Cell fluorescence dropped by approximately 45% when the incubation temperature of the cells was reduced from 37 degrees C to 4 degrees C. Both this phenomenon and a significant reduction in liposome uptake (p < 0.05 and p < 0.01) after incubation with the metabolic inhibitors 2-deoxyglucose and sodium azide indicated active, energy-dependent processes. Phagocytosis in cell-liposome interactions was directly shown by a significant reduction in cell fluorescence (p < 0.05) after application of the actin inhibitor cytochalasin B. The results presented here give concrete data on interactions between liposomes and superficial cells of the eye in vitro.

Animals↗