Biomedical subjects

P Kosmidis

Publications and source records attributed to P Kosmidis.

At least 37 records · Page 2Linked to original sources

PubMed2003

Oral vinorelbine in combination with cisplatin: a novel active regimen in advanced non-small-cell lung cancer.

BACKGROUND: A phase II trial of alternating i.v. and oral vinorelbine in combination with cisplatin was designed to determine the response rate, safety profile, progression-free survival, overall survival and quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-six chemotherapy-naïve patients received cisplatin 100 mg/m(2) and i.v. vinorelbine 25 mg/m(2) on day 1, followed by oral vinorelbine 60 mg/m(2) on days 8, 15 and 22, every 28 days. RESULTS: After an independent review, the response rate was 33% [95% confidence interval (CI) 20% to 46%]. Median progression-free and overall survival were 5.5 months (95% CI 3.7-6.4) and 8.9 months (95% CI 8.8-11.7), respectively. The most frequent hematological toxicities were neutropenia (grade 3-4 in 73% of patients) and anemia (grade 3-4 in 11% of patients). Grade 3-4 infections and non-hematological toxicities occurred occasionally. QoL for lung cancer related symptoms was stable or improved. CONCLUSIONS: The efficacy and safety of the alternating vinorelbine schedule (i.v. on day 1, oral on days 8, 15 and 22) in combination with cisplatin in advanced NSCLC are similar to those of the standard regimen using exclusively i.v. vinorelbine, whereas ease of administration and patient comfort may favor the novel approach.

Administration, Oral↗

PubMed2002

Temozolomide in combination with docetaxel in patients with advanced melanoma: a phase II study of the Hellenic Cooperative Oncology Group.

PURPOSE: Temozolomide is a novel oral alkylating agent that is effective against melanoma. Moreover, temozolomide readily crosses the blood-brain barrier and may consequently be effective in patients with brain metastases. This phase II study was performed to assess the efficacy and safety of the combination regimen of temozolomide and docetaxel in patients with advanced metastatic melanoma. PATIENTS AND METHODS: Sixty-five patients with metastatic melanoma were enrolled. Treatment consisted of intravenous docetaxel (80 mg/m(2)) on day 1 and oral temozolomide (150 mg/m(2)) on days 1 to 5, every 4 weeks, for a maximum of six cycles. RESULTS: Sixty-two patients were eligible for the efficacy and safety analysis. Seventeen patients (27%) achieved an objective response, including five complete (8%) and 12 partial responses (19%). Median response duration was 9.5 months. Among responders, median time to progression (TTP) was 11.2 months and median overall survival (OS) was 16 months. For all treated patients, the median TTP was 4 months and median OS was 11 months. Three (38%) of eight patients who presented with brain metastases had a partial response for 5, 6, and 12 months. Of 52 patients who did not have brain involvement at presentation, only four (8%) developed brain metastases at a median follow-up of 14 months. Myelosuppression was the primary toxicity. CONCLUSION: The combination of temozolomide and docetaxel was effective and well tolerated as first-line treatment for patients with advanced metastatic melanoma and demonstrated encouraging antitumor activity against brain metastases.

Administration, Oral↗

PubMed2002

Neoadjuvant chemotherapy with a combination of pegylated liposomal doxorubicin (Caelyx) and paclitaxel in locally advanced breast cancer: a phase II study by the Hellenic Cooperative Oncology Group.

BACKGROUND: To determine the activity and safety of the combination of paclitaxel and pegylated liposomal doxorubicin (Caelyx) in patients with locally advanced breast cancer. PATIENTS AND METHODS: This was a multicenter phase II study. Thirty-five newly diagnosed patients with locally advanced breast cancer were included in the study. Histological or cytological diagnosis was necessary for inclusion. Median age was 54 years (range 26-73 years). Fifteen patients were premenopausal and 20 postmenopausal. Paclitaxel was administered at a dose of 175 mg/m(2) and pegylated liposomal doxorubicin 35 mg/m(2) every 3 weeks for six cycles. RESULTS: Twenty-five patients (71%) responded. Six (17%) had a complete response, 19 (54%) had a partial response, four remained stable, two progressed and four were not evaluated for response due to discontinuation of chemotherapy. Three patients had a pathologically complete response. A total of 173 cycles were administered. The primary toxicity observed was skin toxicity. Grade 3 skin toxicity was noted in four patients (11%). Palmar-plantar erythrodysesthesia (PPE) grade 3 was experienced by three (9%). Two patients presented with PPE and skin toxicity. Hematological toxicities included grade 3 leukopenia in four patients (3%). Other grade 3 toxicities were uncommon and included only alopecia in 29 patients (83%). Grade 3 or 4 neurotoxicity was not observed in any patient. Dose reduction was necessary in seven patients; in six due to skin toxicity and in one due to neutropenia. Four patients discontinued treatment due to skin toxicity. There were no treatment-related deaths. CONCLUSIONS: The combination of pegylated liposomal doxorubicin and paclitaxel was active in locally advanced breast cancer. The primary toxicity was cutaneous toxicity and it was manageable.

Adult↗

PubMed2002

Vinblastine and interferon-gamma combination with and without 13-cis retinoic acid for patients with advanced renal cell carcinoma. Results of two phase II clinical trials.

BACKGROUND: The aim of this study is firstly to determine the response rates and toxicity of two regimens containing vinblastine (VBL) in combination with interferon-gamma (IFN-gamma) in the treatment of patients with advanced renal cell carcinoma (RCC), and secondly to evaluate the additional efficacy of 13-cis retinoic acid (13-CRA) in RCC. METHODS: Twenty-nine patients were included in the first trial (Trial 1) and 40 in the second one (Trial 2). The therapy given in Trial 1 consisted of VBL 0.15 mg/kg i.v. every 2 weeks and IFN-gamma 100 microg s.c. 3 times weekly. In Trial 2, the therapy consisted of the same two drugs, in the same doses, plus oral 13-CRA 40 mg/day. RESULTS: In Trial 1 there were 3 (10.3%) patients with complete response, 3 (10.3%) patients with partial response, 8 (27.6%) patients with stable disease and 15 (51.7%) patients with progressive disease. In Trial 2, there was no complete response, however, 3 (7.5%) patients had partial response. Additionally, 15 (37.5%) patients maintained stable disease and 14 (35%) patients had progressive disease. In Trial 1, the median survival was 12.56 months (95% CI, 6.8-18.3, range 0.59-42.49) and the median time to progression was 3.21 months (95% CI, 1.7-4.7, range 0.03-42.49). In Trial 2, the median survival was 9.54 months (95% CI, 5.9-13.1, range 0.43-24.1) and the median time to progression was 3.9 months (95% CI, 0.8-7, range 0.26-24.1). In Trial 1, granulocytopenia grade 3 and 4 appeared in 5 (17.2%) patients and anaemia grade 3 in 1 (3.4%) patient. In Trial 2, there were grade 3 toxicities, as granulocytopenia in 5 (12.5%) patients, anemia in 4 (10.0%) patients, stomatitis in 3 (7.5%) patients, fatigue/malaise in 3 (7.5%) patients and 1 (2.5%) had diarrhea. No toxic deaths occurred in both studies. CONCLUSION: The use of IFN-gamma does not enhance the low response of VBL-based chemotherapy. The additional administration of 13-CRA with the combination of VBL and IFN-gamma does not add to the efficacy of this combination in patients with advanced renal cell carcinoma. New active agents are needed to treat patients with this disease.

Adult↗

PubMed2002

Docetaxel in combination with dacarbazine in patients with advanced melanoma.

OBJECTIVES: The number of agents that are active in patients with metastatic melanoma is limited and cure is not a realistic objective for treatment at this stage. The aim of the study was to evaluate the efficacy and safety of new combination regimen cosisting of docetaxel and dacarbazine (DTIC), as first-line chemotherapy, in patients with advanced melanoma. PATIENTS AND METHODS: Patients with advanced melanoma (including cerebral metastases) were eligible. Docetaxel 80 mg/m(2), i.v. over 1 h infusion on day 1, and DTIC 400 mg/m(2), i.v. over 45 min on days 1 and 2, were given every 21 days, for six cycles. All patients were premedicated, prior to each course, with methylprednisolone per os. RESULTS: Forty-one patients entered the study. Thirty-nine were assessable for response and 40 for toxicity. Objective responses were seen in 10 patients (24% of the eligible; 95% CI = 12.4-40.3%, 26% of the assessable and 28% of patients with cerebral metastases were excluded). Three of them achieved a complete response (7%; 95% CI = 1.5-19.9) and 7 a partial response (17%; 95% CI = 7.1-32.0), while 8 patients demonstrated stabilization of their disease (20%; 95% CI = 8.8-34.9). After a median follow-up of 20 months, the median time to progression was 7 months (range 0.5-22) and the median survival was 10 months (1-24+). The main toxicity (G3-4) was neutropenia which occurred in 8/40 (20%) patients. Additional patients had reversible G3-4 toxicities including alopecia, nausea and vomiting and fatigue; 3 of them presented mild to moderate hypersensitivity reactions to docetaxel. No toxic death was noted. CONCLUSIONS: The combination of docetaxel and DTIC is active and well tolerated in patients with advanced melanoma. While this combination is at least as effective as various combination regimens, it does not differ from that reported for single-agent DTIC.

Adult↗

PubMed2001

Dose-dense sequential chemotherapy with epirubicin and paclitaxel versus the combination, as first-line chemotherapy, in advanced breast cancer: a randomized study conducted by the Hellenic Cooperative Oncology Group.

PURPOSE: To compare the efficacy of two different schedules of epirubicin and paclitaxel, as first-line chemotherapy, in patients with advanced breast cancer (ABC). PATIENTS AND METHODS: From October 1997 until May 1999, 183 eligible patients with ABC entered the study. Chemotherapy in group A (93 patients) consisted of four cycles of epirubicin at a dose of 110 mg/m(2) followed by four cycles of paclitaxel at a dose of 225 mg/m(2) in a 3-hour infusion. All cycles were repeated every 2 weeks with granulocyte colony-stimulating factor support. The therapeutic regimen in group B (90 patients) consisted of epirubicin (80 mg/m(2)) immediately followed by paclitaxel (175 mg/m(2) in a 3-hour infusion) every 3 weeks for six cycles. RESULTS: In total, 79 patients (85%) in group A and 72 patients (80%) in group B completed treatment. The median relative dose-intensity of epirubicin was 0.96 in both groups, and that of paclitaxel was 0.96 and 0.97 in groups A and B, respectively. The complete response rate was higher in group A (21.5% v 9% P =.02). Nevertheless, there was no significant difference in the overall response rate between the two groups (55% v 42%, P =.10). Severe neutropenia was more frequently observed with concurrent treatment. After a median follow-up of 16.5 months, median time to progression was 10 months in group A and 8.5 months in group B (P =.27), and median survival was 21.5 and 20 months, respectively (P =.17). CONCLUSION: The present study failed to demonstrate a significant difference in overall response rate between dose-dense sequential administration of epirubicin and paclitaxel compared with the combination of the two drugs given on the same day, even though the sequential treatment resulted in a significantly higher complete response rate.

Adult↗

PubMed2001

A modified mutagenic PCR-RFLP method for K-ras codon 12 and 13 mutations detection in NSCLC patients.

Evidence from many investigators has shown that mutations in the first exon of K- ras gene occur at elevated frequencies in lung, pancreatic and colon carcinoma and seem to be of prognostic importance. The aim of this study was to develop an effective method for the detection of K- ras mutations in codons 12 and 13 in non-small-cell lung cancer (NSCLC) patients in order to investigate correlation with clinical outcome. DNA was extracted from tumour and neighbouring non-neoplastic lung tissues from 70 patients and screened for codon 12 and 13 mutations. We applied a mutagenic PCR-restriction fragment length polymorphism for both codon 12 and 13 mutation detection. Codon 12 mutation was identified in 20% of NSCLC patients, whereas no codon 13 mutation was detected. As expected, the respective non-neoplastic tissues exhibited no mutations. We observed an increased codon 12 mutation prevalence in adenocarcinoma comparing to other types of carcinomas. Follow-up for 29 patients with a mean time of 12 months indicates an increased relapse rate in NSCLC patients with the K- ras codon 12 mutation. Furthermore, a trend towards increased percentage of mutant samples was observed in the advanced stage group of patients. We provide evidence that our approach is a fast and reliable method for screening K- ras exon 1 mutations in tumour samples from NSCLC patients.

Carcinoma, Non-Small-Cell Lung↗

PubMed2001

Predictive factors in radiotherapy for non-small cell lung cancer: present status.

PURPOSE: To evaluate the predictive factors for radiation response in non-small cell lung cancer (NSCLC) and the role of such factors in guiding high dose radiation therapy. METHODS: The first International Workshop on Prognostic and Predictive Factors in Lung Cancer was organized by the Hellenic Cooperative Oncology Group and held in Athens, Greece under the auspices of the International Association for the Study of Lung Cancer. Presentations at this meeting provided the outline of this report, which has also been supplemented with available data from the current literature. RESULTS: The predictive factors for both the natural history and the therapy outcome of NSCLC are grouped as follows: (1) tumor related factors (anatomic factors); the extent of tumor (tumor stage) is one of most important prognostic factors affecting the therapy outcome. Tumor size (T stage), anatomical structures involved (T4 vs. T3 lesion), and the presence of regional lymph node metastasis have a significant impact on both prognosis and response to appropriate therapy; (2) host-related factors (clinical factors) that are important in therapy response include performance status, weight loss of more than 10% of body weight in the previous 6 months, and associated co-morbidities, i.e. pulmonary and cardiac diseases; (3) technical factors of radiation therapy which play a decisive role in successful outcome. The target volume should be defined accurately using modern imaging studies. The radiation dose fractionation schedule, in terms of the dose intensity and total dose, should be high enough to provide local tumor control in the majority of patients. Three-dimensional (3-D) conformal planning is an essential tool in dose escalation studies to determine the maximum tolerated dose of radiation; (4) biological/radiobiological/metabolic factors. Biologic markers resulting from genetic lesions in lung cancer are grouped as follows: (a) oncogene amplification and overexpression (aberrant gene expression) and mutated tumor suppressor genes -- ras gene, myc gene, HER-2/neu and survivin gene, p53 and mutated beta-tubulin gene; (b) tumor biologic/radiobiologic factors -- tumor cell proliferation kinetics, hypoxia, intrinsic cellular radiosensitivity, gamma factor, and DNA content; (c) enzymes and hormones: neuron-specific enolase, serum lactate dehydrogenase, and enhanced glucose metabolic rate supported by increased glucose transporter protein. The surviving fraction of tumor cells at 2.0 Gy of radiation (SF2) as a measure of intrinsic tumor cell radiosensitivity, potential doubling time (T(Pot)) as a measure of the rate of tumor cell proliferation and gamma factor representing the slope of the survival curve at 50% survival rate are being investigated as potential predictors for therapy response. Enhanced glucose utilization, a hallmark of malignant transformation, is being studied as a potential monitor for therapy response by using PET-FDG. CONCLUSION: Current data indicate that there is a dose-response relationship between radiation dose and local tumor control, and also between local tumor control and survival in stage III NSCLC. Therapeutic factors, i.e. total radiation dose, fractionation schedule and dose intensity, and use of 3-D conformal radiation to secure the optimum therapeutic ratio are important for improved local tumor control and survival. Future research should be directed towards radiation dose escalation using 3-D conformal therapy to determine the maximum tolerated dose (MTD) of radiation in chemo-radiotherapy, and the use of this MTD for improved local tumor control and survival. Radiobiological, molecular, and metabolic markers may have potential for monitoring tumor response and optimizing radiation therapy.

Biomarkers, Tumor↗

PubMed2001

Phase II study of temozolomide in heavily pretreated cancer patients with brain metastases.

PURPOSE: To determine the efficacy, tolerability, and safety of temozolomide in heavily pretreated patients with solid tumors and brain metastases. PATIENTS AND METHODS: Twenty-seven of twenty-eight enrolled patients with brain metastases from solid tumors received temozolomide (150 mg/m2/day for five days every 28 days). Twelve patients had non-small-cell lung cancer, five patients had small-cell lung cancer, four patients had breast cancer, and seven patients had other solid tumors. The majority of the patients had multiple metastatic sites, a poor performance status, and had been heavily pretreated. The primary end points were objective response rate, time to progression, and overall survival. Secondary end points included safety and tolerability, and neurologic performance status. RESULTS: A partial response was achieved in 1 (4%) of 24 evaluable patients. Disease stabilization was observed in four (17%) patients. Overall median survival was 4.5 months and median time to progression was 3 months. Improvements in clinical neurologic status were achieved in 10 (37%) patients. Treatment with temozolomide was well tolerated. Four patients had grade 3 nausea and vomiting. No grade 4 toxicity or treatment-related deaths were observed. CONCLUSIONS: Temozolomide demonstrated encouraging activity in the treatment of brain metastases in heavily pretreated patients with solid tumors, and was safe and well tolerated.

Adult↗

PubMed2001

Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG).

BACKGROUND: Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic radiation therapy (HTRT) in limited disease (LD) small cell lung cancer (SCLC) is associated with a high response rate and significant prolongation of survival. Given these results, the Hellenic Cooperative Oncology Group (HeCOG) performed a multicenter randomized phase II study in patients with LD SCLC to evaluate the timing of HTRT (early vs. late) when given concurrently with chemotherapy. PATIENTS AND METHODS: To be eligible for the study, patients were required to have histologically or cytologically proven LD SCLC, confined to one hemithorax and/or ipsilateral mediastinal or supraclavicular lymphnodes and absence of pleural effusion or controlateral supraclavicular lymphnode involvement. Moreover, patients had to have a good performance status and adequate haematological, liver and renal function. Patients with LD SCLC were randomized to receive HTRT either concurrently with the first (Group A) or with the fourth (Group B) cycle of chemotherapy. Chemotherapy consisted of carboplatin administered at an AUC of six given as an i.v. 1-hour-infusion immediately followed by etoposide at a dose of 100 mg/m2 i.v. as a two-hour infusion for three consecutive days every three weeks up to a total of six cycles. Prophylactic cranial irradiation was also given to patients achieving a complete response. RESULTS: 42 and 39 patients, were eligible for efficacy evaluation in group A and B respectively. The overall response rate was 76% in group A and 92.5% in group B (P = 0.07) with a complete response rate of 40.5% and 56.5%, respectively. After a median follow-up of 35 months, time to progression was 9.5 months in group A and 10.5 in group B (NS) while overall median survival was 17.5 and 17 months respectively (NS). The 2-year survival was 36% in group A and 29% in group B (NS) and the 3-year survival 22% and 13%, respectively (NS). The distant relapse rate was 38% in group A and 61% in group B (P = 0.046). Severe grade 3 4 anemia was recorded in 19% of group A and 12.5% of group B (NS), while severe leucopenia was recorded in 35.5% and 20.5% (P = 0.09) and neutropenic fever in 5% and 2.5% (NS), respectively. Severe thrombocytopenia did not differ significantly between the two treatment groups being 21.5% and 23%, respectively. Severe grade 2-3 esophageal toxicity was 19% in group A and 23% in group B (NS), while grade 3 lung toxicity was 5% and 7.5% (NS), respectively. No toxicity-related deaths were recorded. CONCLUSION: Concurrent administration of HTRT with carboplatin etoposide is associated with a high response and survival rate. Although a trend for higher response rate was recorded in the group of patients who received late HTRT, the overall median, 2-year and 3-year survival rates did not differ significantly between the two treatment groups. The toxicity of this promising therapeutic approach was acceptable. Comparative phase III studies with an adequate number of patients are recommended in order to answer this question.

Adult↗

PubMed2001

Weekly paclitaxel as first-line chemotherapy and trastuzumab in patients with advanced breast cancer. A Hellenic Cooperative Oncology Group phase II study.

AIM: To evaluate the activity and acute toxicity of the combination of weekly paclitaxel as first-line chemotherapy and trastuzumab, in patients with HER-2/neu overexpressing advanced breast cancer (ABC). BACKGROUND: Weekly paclitaxel has been shown to be a well tolerated treatment with considerable activity in patients with ABC. Clinical trials with transtuzumab, a humanized anti-p185 HER-2/neu monoclonal antibody have demonstrated that this agent produces objective responses in patients with ABC. PATIENTS AND METHODS: From December 1998 to April 2000, 34 patients with HER-2/neu overexpressing ABC were treated with weekly paclitaxel; given by one-hour infusion at a dose of 90 mg/m2 immediately followed by trastuzumab, 4 mg/kg as a loading dose and 2 mg/kg i.v. given over 30 min, thereafter weekly for at least 12 weeks. Expression of HER-2/neu was determined by immunohistochemical analysis on fixed, paraffin-embedded tissues. Eligible patients were required to have > or = 25% stained tumor cells. RESULTS: Thirty-three patients completed at least 12 weeks of combined treatment. After completion of the 12th week of treatment, four patients (12%) achieved complete and 17 (50%) partial response. Median duration of response was 11.6 months. More frequent side effects included anemia (56%). neutropenia (27%), peripheral neuropathy (78%), diarrhea (30%), alopecia (70%), arthralgias/myalgias (62%), fatigue (59%) and hypersensitivity reactions (62%). Median time to progression was nine months while median survival had not been reached CONCLUSIONS: The combination of weekly paclitaxel and trastuzumab is a safe and active regimen for patients with HER-2/neu overexpressing ABC. Randomized phase III studies with this combination are warranted.

Adult↗

PubMed2001

Dose-dense sequential chemotherapy with epirubicin and paclitaxel in advanced breast cancer.

The purpose of this study was to evaluate the activity and toxicity profile of dose-dense sequential chemotherapy with epirubicin (EPI) and paclitaxel in advanced breast cancer (ABC). From January to September 1997, 41 patients with recurrent or metastatic (stage IV) breast cancer were enrolled in the study. Their median age was 57 (range, 33-77) years and median performance status 0 (range, 0-2). Twenty patients had received adjuvant chemotherapy. The chemotherapeutic regimen consisted of 4 cycles of EPI 110 mg/m2 every 2 weeks followed by 4 cycles of paclitaxel, 225 mg/m2 over 3 hours every 2 weeks. G-CSF was administered prophylactically on days 2-10 of each cycle. 34 (83.0%) patients completed all 8 cycles of chemotherapy. A total of 304 cycles were administered, 259 (85.0%) of them at full dose. Thirty (10.0%) cycles were delivered with a delay. The relative median dose intensities of EPI and paclitaxel were 0.95. Most common grade 3-4 side effects were anemia (15.0%) neutropenia (12.0%), thrombocytopenia (5.0%), nausea/vomiting (10.0%), febrile neutropenia (7.5%), and alopecia (90.0%). Overall, 8 (19.5%) patients achieved a complete and 15 (36.5%) a partial response. Median duration of response was 8.4 (range, 3.1-15.5+) months. After a median follow-up of 18.5 months, median time to progression was 8.7 (range, 0.5-21+) months; median survival has not been reached yet. Dose-dense sequential chemotherapy with EPI and paclitaxel shows promising activity as first-line treatment in ABC. Randomized studies comparing this type of chemotherapy with the classical administration of the two drugs together every 3 weeks are ongoing.

Adult↗

PubMed2000

Ifosfamide plus oral etoposide salvage chemotherapy for platinum-resistant paclitaxel-pretreated ovarian cancer.

BACKGROUND: The prognosis of platinum resistant ovarian cancer is very poor and the treatment of choice has not been clearly defined. PATIENTS AND METHODS: We conducted a phase II study with the combination of ifosfamide i.v. at 2.25 g/m2 (days 1, 2) and etoposide per os at 100 mg daily (days 1-10) every four weeks. To be eligible for the study patients had to be resistant to platinum and paclitaxel pretreated. RESULTS: Forty-one patients entered the study. The median interval from the previous chemotherapy was 3.9 months. The median number of previous chemotherapeutic regimens was 2. Severe toxicities included neutropenia (41% of patients), leukopenia (29%) and thrombocytopenia (13%). Thirty-five patients are assessable for response. Nine patients responded (22% of the eligible, 26% of the assessable), four of them demonstrated complete response to chemotherapy (10% and 12%, respectively), while three patients demonstrated stabilization of their progressive disease. After a median follow-up of 18 months, time to progression is 3 months (range 0.9-14.4), duration of response is 9 months (2.5-11) and median survival is 13 months (2.5-37.4+). CONCLUSIONS: The combination of ifosfamide with oral etoposide appears to have significant but manageable toxicity and encouraging efficacy in platinum resistant ovarian cancer.

Administration, Oral↗

PubMed2000

Gemcitabine and vinorelbine as second-line treatment in patients with metastatic breast cancer progressing after first-line taxane-based chemotherapy: a phase II study conducted by the Hellenic Cooperative Oncology Group.

BACKGROUND: Gemcitabine and vinorelbine have shown activity in breast cancer. A phase II trial was initiated in order to evaluate the response rate (RR) and time to progression (TTP) of the combination of the two drugs in patients with metastatic breast cancer progressing after first-line taxane-based chemotherapy. PATIENTS AND METHODS: Thirty-one patients were treated with the combination of gemcitabine 1000 mg/m2 days 1 + 8 and vinorelbine 30 mg/m2 days 1 + 8. The cycles were repeated every three weeks. RESULTS: Of 27 evaluable patients 1 (4%, 95% confidence interval (95% CI): 0.1%-19%) achieved complete remission (CR), five (18%; 95% CI: 6%-38%) partial remission (PR), eleven (40%; 95% CI: 22%-61%) stable disease and ten patients progressed. The median duration of response was six months (range 4-10+) and the median duration of disease stabilization was five months (range 2-22+). With a median follow-up of 16 months (range 0.4-22+) the median TTP was 3.5 months (range 0.4-22+) and the median survival was 9.5 months (range 0.4-22+). Grade 3-4 toxicities were granulocytopenia 15 patients (48%), rash 3 patients (10%), neuropathy 1 patient (3%) and thrombocytopenia 1 patient (3%). In conclusion the combination of gemcitabine/vinorelbine in the doses administered in this group of patients had a response rate of 22% and needs to be further evaluated in metastatic breast cancer.

Adult↗

PubMed2000

Paclitaxel (175 mg/m2) plus carboplatin (6 AUC) versus paclitaxel (225 mg/m2) plus carboplatin (6 AUC) in advanced non-small-cell lung cancer (NSCLC): a multicenter randomized trial. Hellenic Cooperative Oncology Group (HeCOG).

PURPOSE: The combination of paclitaxel and carboplatin has become a widely used regimen in NSCLC due to phase II reports of moderate toxicity, reasonable activity and easy outpatient administration. Purpose of our present prospective study was to evaluate the dose response relationship of paclitaxel. PATIENTS AND METHODS: Since July 1996, 198 patients with non-operable NSCLC and measurable disease without previous chemotherapy entered the trial. Ninety nine patients (group A) were randomized to receive paclitaxel 175 mg/m2 in three-hour infusion plus carboplatin dosed to an area under the concentration-time curve of 6 every 3 weeks and 99 (group B) to receive the same regimen with paclitaxel increased to 225 mg/m2. Eligibility criteria included WHO performance status 0-2, documented inoperable stage IIIA and IIIB, IV, no brain metastasis, no prior chemotherapy and adequate renal and hepatic function. Patients in both groups were well-matched with baseline disease characteristics. RESULTS: In group A with 90 evaluable patients, the response rate was 25.6% (6 CR, 17 PR) whereas in group B with 88 evaluable patients, the response rate was 31.8% (3 CR, 25 PR), P = 0.733. Median time to progression favored the high-dose paclitaxel (4.3 vs. 6.4 months, P = 0.044). The median survival was 9.5 months for group A versus 11.4 months for group B (P = 0.16). The one-year survival was 37% for group A and 44% for group B (P = 0.35). The best prognostic factor for one-year survival was the response rate (P < 0.0001). With a relative dose intensity of paclitaxel 0.94 in both groups, neurotoxicity (P = 0.025) and leucopenia (P = 0.038) were more pronounced in group B patients. No toxic death was observed. CONCLUSIONS: Higher dose paclitaxel prolongs the median time to progression but causes more neurotoxicity and leucopenia. The better response rate, the longer overall and better one-year survival seen with the higher dose of paclitaxel are not statistically significant.

Adult↗

PubMed2000

Phase II study of pegylated liposomal doxorubicin: inactive in recurrent small-cell lung cancer. A Hellenic Cooperative Oncology Group Study.

PURPOSE: Although clinical experience with liposomal doxorubicin is still limited in solid tumours, single agent Caelyx (pegylated liposomal doxorubicin) treatment has shown promising results in AIDS-related Kaposi's sarcoma, metastatic breast and ovarian cancer and anecdotally in other solid tumours. This is the first report of its use in small-cell lung cancer (SCLC). The objective of this multicenter phase II study was to evaluate the safety, tolerance and anti-tumour activity of Caelyx as monotherapy in patients with recurrent SCLC. PATIENTS AND METHODS: A total of 14 patients with recurrent SCLC who had not received prior treatment with doxorubicin, were accrued into this phase II study. All patients had progressed or relapsed after first-line chemotherapy. All but one had achieved objective responses to first-line treatment with median duration of five months (range 2-18 months) but half of them had experienced 'refractory' relapses (within 3-4 months). Study treatment consisted of Caelyx 50 mg/m2 (1-hour i.v infusion every 4 weeks for 6 cycles). RESULTS: No responses were seen but in three patients disease was stabilised for a median of three months. The median number of cycles was 2 per patient, with 11 of 14 patients not completing 6 cycles of Caelyx treatment. From those, five patients were removed from the study after only one cycle due to rapid disease progression, and one was withdrawn after three cycles due to prolonged toxicity. Overall, treatment was well tolerated with no episodes of grade 4 toxicity and only two episodes of grade 3 toxicities: one of thrombocytopenia and one of prolonged palmar-plantar erythrodysesthesia (PPE). CONCLUSIONS: These results demonstrate limited activity of Caelyx in this patient population, which may be related to the poor prognostic features of such patients. Our findings are in agreement with previous observations that doxorubicin-containing combinations are rarely active in platinum/etoposide failures. However, as in other studies the favourable toxicity profile of Caelyx is confirmed.

Aged↗

PubMed2000

Combined treatment with low-dose interferon plus vinblastine is associated with less toxicity than conventional interferon monotherapy in patients with metastatic renal cell carcinoma.

The outcome of treatment of advanced renal cell carcinoma is disappointing. In interferon (IFN)-treated patients, the high incidence of adverse effects causes many patients to withdraw from treatment. This 12-week randomized study compared the incidence of toxicity associated with high-dose IFN monotherapy (15 x 10(6) U thrice weekly) and treatment with the combination of low-dose IFN (5 x 10(6) U thrice weekly) and 6 mg/m2 vinblastine (VBL) every 14 days in 100 consecutive patients. There was no significant difference in response rate between treatment arms (42% IFN vs. 34% IFN + VBL) or between subgroups (by tumor location). Combined treatment was associated with a significantly lower incidence of fever, fatigue, and weight loss but with a higher incidence of leukopenia. There was no significant difference in the incidence of other events. More patients treated with IFN monotherapy required bed rest, and overall treatment costs were 60% higher than for combined treatment. It is concluded that combined treatment with low-dose IFN and VBL, without loss of short-term efficacy, is better tolerated and less expensive than high-dose IFN monotherapy.

Adult↗

PubMed2000

Fluorouracil and leucovorin with or without interferon alfa-2a as adjuvant treatment, in patients with high-risk colon cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group.

BACKGROUND: It has been shown in randomized studies that adjuvant treatment with the combination of fluorouracil (FU) and levamisole reduced the risk of recurrence and deaths of patients with stage III colon cancer. Pharmacological studies of FU led to its use in combination with a number of modulating agents including interferon-alpha and leucovorin (LV) that appear to enhance its activity in vitro. Furthermore, a meta-analysis suggested that the combination of FU with LV increased the response rate as compared to FU monotherapy in patients with advanced colorectal cancer. PURPOSE: To evaluate the impact of adjuvant treatment with the combination of FU and LV with or without interferon alfa-2a (IFN) on disease-free survival (DFS) and overall survival (OS) for patients with stage II or III colon cancer. PATIENTS AND METHODS: From August 1989 to July 1997, 280 patients with stage II and III colon cancer entered the study and were randomly assigned to receive either the combination of FU (600 mg/m(2)/week x 6, followed by a 2-week rest) and LV (500 mg/m(2)/week x 6 as a 2-hour infusion, followed by a 2-week rest) for 4 cycles (group A, 139 patients), or the same chemotherapy plus recombinant IFN (3 MU subcutaneously 3 times a week) for 1 year (group B, 141 patients). RESULTS: A total of 109 patients (78.9%) of group A and 119 (84.4%) of group B completed four cycles of chemotherapy. Also, 51.4% of patients of group A and 53.9% of group B received > or =80% of the planned dose of FU. One patient (group A) was found to be ineligible and was not included in the analysis. The median relative dose intensity of FU in the two groups was 0.90 and 0.85, respectively. As of August 1998, after a median follow up of 4 years, there was no significant difference in either 3-year DFS (group A, 83.1%; group B, 75.9%, p = 0.14) or OS (group A, 84.5%; group B, 80.0%, p = 0.27). In the Cox model, stage of disease, number of infiltrated nodes, tumor grade and presence of regional implants were identified as significant prognostic factors for OS. Grade 3-4 toxicities, mainly diarrhea, were observed in 26.1% of patients of group A and in 24.8% of group B. There were no treatment-related deaths. CONCLUSIONS: The addition of IFN to the combination of FU with LV postoperatively does not improve DFS and OS of patients with stage II or III colon cancer.

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