Biomedical subjects

Vassilis Georgoulias

Publications and source records attributed to Vassilis Georgoulias.

At least 19 recordsLinked to original sources

PubMed2007

Short-term exposure of cancer cells to micromolar doses of paclitaxel, with or without hyperthermia, induces long-term inhibition of cell proliferation and cell death in vitro.

BACKGROUND: During intraoperative hyperthermic intraperitoneal chemotherapy for primary or secondary peritoneal malignancies, tumor cells are exposed to high drug concentrations for a relatively short period of time. We investigated in vitro the effect of paclitaxel and hyperthermia on cell proliferation, cell cycle kinetics and cell death under conditions resembling those during intraoperative hyperthermic intraperitoneal chemotherapy. METHODS: Human breast MCF-7, ovarian SKOV-3 and hepatocarcinoma HEpG2 cells were exposed to 10 and 20 microM paclitaxel at 37, 41.5 or 43 degrees C for 2 h. Cell proliferation, cell cycle kinetics, necrosis and apoptosis were evaluated. RESULTS: Hyperthermia exerted a cytostatic effect to all cell lines and at 43 degrees C a cytotoxic effect on MCF-7 cells. MCF-7 and SKOV-3 cells treated under normothermic conditions with paclitaxel were arrested at G2/M or M phase for at least 3 days. Most of MCF-7 cells and approximately half of SKOV-3 cells were in interphase and became multinucleated without properly completing cytokinesis. Hyperthermia at 41.5 degrees C altered cell cycle distribution and affected the paclitaxel-related effect on cell cycle kinetics of MCF-7 and SKOV-3 cells. Analysis of the mode of cell death showed that cell necrosis prevailed over apoptosis. Hyperthermia at 43 degrees C increased paclitaxel-mediated cytotoxicity in MCF-7 cells and to a lesser extent in SKOV-3 and HEpG2 cells. CONCLUSIONS: Short-time treatment of carcinoma cells with high (micromolar) concentrations of paclitaxel in normothermic and hyperthermic conditions is highly efficient for cell growth arrest and could be of clinical relevance in locoregional chemotherapy.

Antineoplastic Agents, Phytogenic↗

PubMed2006

Oxaliplatin as first-line treatment in inoperable biliary tract carcinoma: a multicenter phase II study.

BACKGROUND: A multicenter phase II study was conducted in order to evaluate the efficacy and safety of oxaliplatin as first-line treatment of patients with locally advanced or metastatic carcinoma of the biliary tract. PATIENTS AND METHODS: Twenty-nine chemo-naïve patients with locally advanced or metastatic biliary tract carcinoma received oxaliplatin 130 mg/m(2) i.v. every 21 days. Patients were treated until tumor progression or unacceptable toxicity. RESULTS: An objective response (3 complete responses, 3 partial responses) was achieved in 6 patients (20.6%, 95% CI 5.95-35.4). Disease control (complete response, partial response and stable disease) was observed in 14 patients (48.2%). The median time to tumor progression was 3 months (range 0.7-39) and the median overall survival was 7 months (range 1-39). The 1-year survival rate was 32%. Toxicity was mild. CONCLUSION: Oxaliplatin is an active agent against biliary tract carcinoma and therefore should be further investigated in combination with other cytotoxic drugs.

Adult↗

PubMed2006

Gemcitabine plus oxaliplatin combination (GEMOX regimen) in pretreated patients with advanced non-small cell lung cancer (NSCLC): a multicenter phase II study.

PURPOSE: To evaluate the activity and tolerance of gemcitabine in combination with oxaliplatin (GEMOX regimen) in pretreated patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-two patients with advanced NSCLC who had disease progression after a cisplatin- and taxane-based front-line regimen were treated with gemcitabine (1500 mg/m(2) on days 1 and 8) and oxaliplatin (130 mg/m(2) on day 8) every 3 weeks. The patients' median age was 62 years and the performance status (WHO) was 0 for 11, 1 for 17 and 2 for 4 patients. The treatment was second line for 22 (69%) and >or=third line for 10 (31%) patients. RESULTS: Partial response was achieved in 5 (16%) patients, stable disease in 8 (25%) and progressive disease in 19 (59%). Two patients with stable disease and one patient with progressive disease while on previous chemotherapy experienced a partial response with GEMOX regimen. The median duration of response was 2.5 months (range, 1-11.5), the median time to tumor progression 3 months (range, 1-18) and the median survival 5.6 months (range, 1-31). Grade III neutropenia occurred in five (16%) patients, grade III thrombocytopenia in two (6%) and grade III anemia in three (9%); moreover, grades II-III asthenia was reported in eight (25%) patients and grades II-III neurotoxicity in three (9%). CONCLUSION: The GEMOX combination is a relatively active and well tolerated second-line regimen in NSCLC patients pretreated with a taxane- and/or platinum-based chemotherapy.

Adult↗

PubMed2006

A highly specific real-time RT-PCR method for the quantitative determination of CK-19 mRNA positive cells in peripheral blood of patients with operable breast cancer.

The aim of the present study was to decrease the incidence of false positives and to better characterize marginally cytokeratin-19 (CK-19) mRNA positive peripheral blood samples from patients with early stage breast cancer. A new set of highly specific primers for CK-19, which avoids amplification of contaminating genomic DNA, was designed and evaluated to improve the specificity and sensitivity of the previously described methodology. The primers were specifically designed to avoid amplification of contaminating genomic DNA and CK-19 pseudogenes. The breast cancer cell line MCF-7 was used as positive control for the development and analytical evaluation of the assay, while peripheral blood samples from 62 healthy female individuals and 160 patients with early breast cancer were used for the evaluation of the sensitivity and specificity of the new primer pair. The novel designed primer pair was highly sensitive, as it detects up to 1 MCF-7 cell, and specific as none of the healthy individuals had detectable CK-19 mRNA positive cells in their peripheral blood. CK-19 mRNA positive cells were detected in 33 out of 160 (20.6%) patients with early breast cancer. Results obtained by the proposed optimized real-time RT-PCR protocol correlated well with those obtained in the same samples by our previously reported quantitative real-time RT-PCR [concordance in 198/222 (89.2%), p = 0.0022, McNemar test]. The improved method eliminates the incidence of false positives and is highly sensitive and specific. The method could be used in a clinical setting in the near future for continuous monitoring and quantification of circulating epithelial cells in the peripheral blood of patients with operable breast cancer, provided that a quite larger number of clinical samples with a known follow-up will be analyzed.

Adolescent↗

PubMed2006

Detection of Mammaglobin A-mRNA-positive circulating tumor cells in peripheral blood of patients with operable breast cancer with nested RT-PCR.

OBJECTIVES: The development and validation of a nested RT-PCR methodology for the detection of Mammaglobin A-mRNA-positive circulating tumor cells in peripheral blood of patients with operable breast cancer and evaluation of its prognostic significance. DESIGN AND METHODS: Different combinations of specific primers were in silico designed and selected, so that false positive results due to genomic DNA contamination were avoided. The specificity of the primers used was evaluated in 30 healthy individuals, 20 patients with colorectal cancer and 20 patients with non-small cell lung cancer. The method was applied in 101 patients with operable breast cancer before the administration of adjuvant chemotherapy and 39 patients with metastatic breast cancer. RESULTS: Mammaglobin A-mRNA-positive cells were detected in 14/101 (13.9%) of early breast cancer patients but not in the control population studied (0%); 9 of them (64.3%) relapsed during the follow-up period. Mammaglobin A was detected in 7/39 (17.9%) of patients with verified metastasis. Multivariate analysis revealed the detection of Mammaglobin A-mRNA-positive cells, as an independent risk factor for reduced DFI. CONCLUSIONS: Mammaglobin A is a highly specific molecular marker for the detection of circulating tumor cells in operable breast cancer, with important prognostic applications.

Biomarkers, Tumor↗

PubMed2006

HER-2 DNA quantification of paraffin-embedded breast carcinomas with LightCycler real-time PCR in comparison to immunohistochemistry and chromogenic in situ hybridization.

OBJECTIVES: To compare the detection of HER-2 status by real-time PCR, on paraffin-embedded breast carcinomas, in respect to immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH). DESIGN AND METHODS: Paraffin-embedded breast carcinomas collected from 85 patients diagnosed with early stage breast cancer were analyzed for HER-2 gene amplification by real-time PCR and CISH, as well as for HER-2 protein expression by IHC. RESULTS: HER-2 gene amplification was observed in 19 (22.4%) of 85 breast cancer patients by real-time PCR and in 19 (22.4%) of 85 patients by CISH. Strong (3+) HER-2 protein over-expression was observed in 13 (15.3%) out of 85 patients. Moreover, there were 4 out of 85 (4.7%) patients that had moderate (2+) HER-2 protein over-expression, while 68 out of 85 (80%) patients had no HER-2 protein over-expression by IHC. There were strong concordance rates between real-time PCR and IHC (79/85, 92.9%, p<0.0001) and real-time PCR and CISH (77/85, 90.6%, p<0.0001). The concordance rate between the three methods was 90.6% (p<0.0001). CONCLUSIONS: Our data show that the results obtained for amplification of HER-2 by real-time PCR on the LightCycler are comparable to those obtained by IHC and CISH.

Breast Neoplasms↗

PubMed2006

Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients.

PURPOSE: To evaluate the predictive and prognostic value of peripheral blood cytokeratin-19 (CK-19) mRNA-positive cells in axillary lymph node-negative breast cancer patients. PATIENTS AND METHODS: Peripheral blood was obtained from 167 node-negative breast cancer patients before the initiation of any systemic adjuvant therapy, and was analyzed for the presence of CK-19 mRNA-positive cells using a real time polymerase chain reaction assay. The association with known prognostic factors and the effect of CK-19 mRNA-positive cells on patients' prognosis was investigated. RESULTS: CK-19 mRNA-positive cells were detected in the blood of 36 (21.6%) of the 167 patients. There was no correlation between the detection of CK-19 mRNA-positive cells in the peripheral blood and the various known pathologic and clinical prognostic factors; only overexpression of HER2 receptor (score 2+/3+) on the primary tumor was associated with a higher incidence of CK-19 mRNA-positive cell detection (P = .033). Multivariate analysis revealed that detection of peripheral blood CK-19 mRNA-positive cells was associated with early clinical relapse (P < .00001) and disease-related death (P = .008). CONCLUSION: Detection of peripheral-blood CK-19 mRNA-positive cells is an independent predictive and prognostic factor for reduced disease-free interval and overall survival, respectively, in node-negative breast cancer patients.

Adult↗

PubMed2006

Pegylated liposomal doxorubicin in combination with vinorelbine as salvage treatment in pretreated patients with advanced breast cancer: a multicentre phase II study.

PURPOSE: To investigate the activity and tolerance of pegylated liposomal doxorubicin in combination with vinorelbine in pretreated patients with metastatic breast cancer. PATIENTS AND TREATMENT: Thirty-six women with metastatic breast cancer were enrolled. The median age was 64 years, 80% of the patients had a performance status of 0-1, 30 (83%) had visceral disease and 83% had received prior taxanes while 50% anthracyclines. Treatment consisted of pegylated liposomal doxorubicin (40 mg/m2 on day 1) and vinorelbine (25 mg/m2 on days 1 and 15) every 4 weeks. RESULTS: In an intention-to-treat analysis 2 (6%) complete and 12 (33%) partial responses were observed (overall response rate 39%; 95% CI: 23-54.8%); 8 (22%) and 14 (39%) patients experienced stable and progressive disease, respectively. The median TTP was 6.5 months and the median survival time 14.2 months. The 1-year survival rate was 54.1%. Grade 3 and 4 neutropenia occurred in 21 (58%) patients, grade 3-4 anemia in four (11%) and grade 4 thrombocytopenia in one (3%). Two (6%) patients developed febrile neutropenia. Non-hematologic toxicity was mild and easily manageable. There was no clinically important cardiac toxicity or treatment-related deaths. CONCLUSIONS: The combination of pegylated liposomal doxorubicin and vinorelbine is an active and well tolerated salvage regimen in patients with metastatic breast cancer which merits further evaluation.

Adult↗

PubMed2006

A multicenter phase II study of sequential vinorelbine and cisplatin followed by docetaxel and gemcitabine in patients with advanced non-small cell lung cancer.

PURPOSE: To evaluate the activity and toxicity of the sequential administration of vinorelbine/cisplatin (VC regimen) followed by the docetaxel/gemcitabine (DG regimen) combination in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND TREATMENT: Fifty-nine previously untreated patients with advanced/metastatic NSCLC received three cycles of cisplatin 80 mg/m(2) (day 1), and vinorelbine 30 mg/m(2) (days 1 and 8 every 3 weeks; VC regimen), followed by six cycles of docetaxel (65 mg/m(2), day 1) and gemcitabine (1,500 mg/m(2), day 1), (DG regimen) every 2 weeks. RESULTS: One (1.7%) complete and 26 (44.1%) partial responses were achieved for an overall response rate of 45.8% (95% CI 33.05-58.48%); 12 (20.3%) patients had stable disease and 20 (33.9%) progressive disease. The median time to progression was 5.3 months, the median survival time 12.5 months and the 1-year survival rate 51%. The main toxicity was grade III/IV neutropenia occurring in 25.5% of patients; all other hematologic and non-hematologic toxicities were relatively infrequent. CONCLUSIONS: The sequential administration of VC and DG regimens was well tolerated and active against advanced NSCLC and merits to be further evaluated against a single doublet.

Adult↗

PubMed2006

Coadministration of oxaliplatin does not influence the pharmacokinetics of gemcitabine.

We investigated the possible pharmacokinetic interactions of gemcitabine and oxaliplatin in patients with advanced solid tumors. Ten patients with advanced stage solid tumors were treated with gemcitabine (1500 mg/m) as a 30-min intravenous infusion on days 1 and 8, followed by oxaliplatin (130 mg/m) as a 4-h intravenous infusion, on day 8 every 21 days. Pharmacokinetic data for 24 h after dosing were obtained for both day 1 (gemcitabine without oxaliplatin coadministration) and day 8 (gemcitabine with oxaliplatin) during the first cycle of treatment. Gemcitabine levels in plasma were quantified using a reverse-phase high-performance liquid chromatography assay with ultraviolet detection, and total and ultrafiltrated platinum levels by flameless atomic absorption spectrophotometry with deuterium correction. All pharmacokinetic parameters of gemcitabine seemed to be unchanged when coadministered with oxaliplatin (day 8) compared with pharmacokinetic data of gemcitabine given as a single agent (day 1). The mean (maximum) concentration of gemcitabine on days 1 and 8 was 13.57 (+/-7.42) and 10.23 (+/-5.21) mg/l, respectively (P=0.28), and the mean half-life was 0.32 and 0.44 h, respectively (P=0.40). Similarly, the P-values for AUC0-24 and the observed clearance were 0.61 and 0.30, respectively. Plasma total and free platinum levels were in agreement with other published data. Gemcitabine disposition appeared to be unaffected by oxaliplatin coadministration because no significant changes in pharmacokinetics between day 1 (gemcitabine without oxaliplatin coadministration) and day 8 (gemcitabine with oxaliplatin) were observed.

Adolescent↗

PubMed2006

Central nervous system relapse in patients with breast cancer is associated with advanced stages, with the presence of circulating occult tumor cells and with the HER2/neu status.

INTRODUCTION: To evaluate the incidence of central nervous system (CNS) involvement in patients with breast cancer treated with a taxane-based chemotherapy regimen and to determine predictive factors for CNS relapse. METHODS: The medical files of patients with early breast cancer (n = 253) or advanced stage breast cancer (n = 239) as well of those with other solid tumors (n = 336) treated with or without a taxane-based chemotherapy regimen during a 42-month period were reviewed. HER2/neu overexpression was identified by immunohistochemistry, whereas cytokeratin 19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in the peripheral blood were identified by real-time PCR. RESULTS: The incidence of CNS relapse was similar in patients suffering from breast cancer or other solid tumors (10.4% and 11.4%, respectively; P = 0.517). The incidence of CNS relapse was significantly higher in breast cancer patients with advanced disease (P = 0.041), visceral disease and bone disease (P = 0.036), in those who were treated with a taxane-containing regimen (P = 0.024), in those with HER2/neu-overexpressing tumors (P = 0.022) and, finally, in those with detectable CK-19 mRNA-positive CTCs (P = 0.008). Multivariate analysis revealed that the stage of disease (odds ratio, 0.23; 95% confidence interval, 0.007-0.23; P = 0.0001), the HER2/neu status (odds ratio, 29.4; 95% confidence interval, 7.51-101.21; P = 0.0001) and the presence of CK-19 mRNA-positive CTCs (odds ratio, 8.31; 95% confidence interval, 3.97-12.84; P = 0.001) were independent predictive factors for CNS relapse. CONCLUSION: CNS relapses are common among breast cancer patients treated with a taxane-based chemotherapy regimen, patients with HER2/neu-positive tumor and patients with CK-19 mRNA-positive CTCs.

Adult↗

PubMed2006

A retrospective analysis of second-line chemotherapy or best supportive care in patients with advanced-stage non-small-cell lung cancer.

BACKGROUND: We retrospectively evaluated the clinical characteristics and outcome of patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) enrolled in first-line chemotherapy trials conducted by our group with respect to receiving or not receiving subsequent treatment. PATIENTS AND METHODS: Data were collected from 634 patients with stage IIIB/IV NSCLC treated with platinum and nonplatinum agent-based first-line regimens. Patient survival was calculated from the day of registration to first-line chemotherapy trials (OS1) as well as from the day of first-line treatment failure or the initiation of second-line chemotherapy (OS2) until death. The decision for administering second-line chemotherapy was, in all cases, at the discretion of the physician. Two hundred twenty-four patients (35.3%) received second-line chemotherapy (second-line group) in the context of second-line clinical trials run by the same group, and 410 (64.7%) received best supportive care (BSC group). There were significant differences between second-line and BSC groups in terms of age, histology, early discontinuation of first-line chemotherapy, and performance status after first-line treatment. RESULTS: Three (1.3%) complete and 25 (11.2%) partial responses to second-line chemotherapy were observed for an overall response rate of 12.5% (95% confidence interval, 8.2%-16.8%). The median OS1 was 13 months and 7 months (P < 0.001) and the OS2, 7 months and 3 months (P < 0.001) for the second-line and BSC groups, respectively. Multivariate analysis revealed that good performance status, disease stage IIIB, response to first-line treatment, and late termination of first-line chemotherapy were significantly associated with increased survival. The administration of second-line chemotherapy was also independently correlated with better outcome. CONCLUSION: The second-line chemotherapy and BSC groups represent different populations of patients with NSCLC. Factors indicative of increased probability of survival could be used to identify the subgroup of patients most likely to benefit from second-line chemotherapy.

Adult↗

PubMed2005

Micromolar taxol, with or without hyperthermia, induces mitotic catastrophe and cell necrosis in HeLa cells.

PURPOSE: Although the mode of action of taxol, when used in nanomolar or micromolar concentrations during long periods, is extensively studied, there are few data available on taxol-mediated cytotoxicity when the drug is applied for a short time alone or in combination with hyperthermia. We studied the effect of taxol and hyperthermia on cell cycle kinetics, proliferation, and mode of cell death in human cervical carcinoma HeLa cells, following a scheme which resembles the one currently used in regional chemotherapy. METHODS: Cells were incubated with micromolar doses of taxol for two h under normothermic or hyperthermic conditions and then cultured in drug-free medium for several days. Cell viability was assessed via an MTT assay. Necrotic and apoptotic cell death was determined using Trypan blue staining and TUNNEL assay, respectively. Flow cytometry was used for the analysis of cell cycle kinetics and the counting of apoptotic cells. Mitotic index, nuclear morphology and nuclear envelope organization were analyzed by fluorescence microscopy. RESULTS: Cells exposed to micromolar doses of taxol for 2 h and then transferred to a drug-free medium for 24 h were arrested at G2/M or M phase. When treated cells were cultured in normal media for longer periods, most of them remained in a tetraploid state, became multinucleated without properly completing cytokinesis and died mostly by necrosis. Hyperthermia alone exerted a cytotoxic effect, inhibited proliferation and caused minor changes in cell cycle kinetics. When combined with taxol treatment, hyperthermia modified the cell cycle-arresting effects of the drug, but did not alter significantly taxol-mediated cytotoxicity. CONCLUSIONS: From these data we conclude that short time incubation of HeLa cells under normothermic or hyperthermic conditions with micromolar concentrations of taxol is sufficient enough to induce extended cell growth arrest and cell death by necrosis.

Antineoplastic Agents, Phytogenic↗

PubMed2005

Capecitabine as adjuvant treatment for stage III colon cancer.

BACKGROUND: Intravenous bolus fluorouracil plus leucovorin is the standard adjuvant treatment for colon cancer. The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer. We evaluated capecitabine in the adjuvant setting. METHODS: We randomly assigned a total of 1987 patients with resected stage III colon cancer to receive either oral capecitabine (1004 patients) or bolus fluorouracil plus leucovorin (Mayo Clinic regimen; 983 patients) over a period of 24 weeks. The primary efficacy end point was at least equivalence in disease-free survival; the primary safety end point was the incidence of grade 3 or 4 toxic effects due to fluoropyrimidines. RESULTS: Disease-free survival in the capecitabine group was at least equivalent to that in the fluorouracil-plus-leucovorin group (in the intention-to-treat analysis, P<0.001 for the comparison of the upper limit of the hazard ratio with the noninferiority margin of 1.20). Capecitabine improved relapse-free survival (hazard ratio, 0.86; 95 percent confidence interval, 0.74 to 0.99; P=0.04) and was associated with significantly fewer adverse events than fluorouracil plus leucovorin (P<0.001). CONCLUSIONS: Oral capecitabine is an effective alternative to intravenous fluorouracil plus leucovorin in the adjuvant treatment of colon cancer.

Adult↗

PubMed2005

Vinorelbine plus cisplatin versus docetaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III randomized trial.

PURPOSE To compare the activity and tolerability of docetaxel/gemcitabine (DG) and vinorelbine/cisplatin (VC) combinations in chemotherapy-naive non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS Patients with advanced NSCLC were randomly assigned to receive either DG (gemcitabine 1,000 mg/m(2) [days 1 and 8] plus docetaxel 100 mg/m(2) [day 8]) or VC (vinorelbine 30 mg/m(2) [days 1 and 8] plus cisplatin 80 mg/m(2) [day 8]) and prophylactic recombinant human granulocyte colony-stimulating factor (150 microg/m(2) subcutaneously [day 9 through 15]) every 3 weeks. Results A total of 413 randomly assigned patients were analyzed for response and toxicity (DG, n = 197; VC, n = 192). Median survival was 9.0 and 9.7 months (P = .965) for DG and VC arms, respectively; the corresponding 1-year survival rates were 34.3% and 40.8%, respectively. Overall response rate was 30% (95% CI, 23.9% to 36.3%) and 39.2% (95% CI, 32.5% to 45.9%; P = .053) for DG and VC, respectively. Toxicity was as follows (DG v VC): grade 2 to 4 anemia, 34% v 55% (P = .0001); grade 3 to 4 neutropenia, 16% v 37% (P = .0001); febrile neutropenia, 6% v 11% (P = .009); and grade 3 to 4 nausea and vomiting, 1% v 15% (P = .003). Nephrotoxicity occurred in 8% and ototoxicity in 2% of VC-treated patients. There were five and six treatment-related deaths in the DG and VC arms, respectively. Quality of life was improved in DG but not in VC patients. CONCLUSION Although the two regimens produced comparable overall survival, the DG regimen had a better toxicity profile. Therefore, DG could be used in the first-line setting of advanced NSCLC, especially for patients who cannot tolerate cisplatin.

Adult↗

PubMed2005

NSCLC--platinum or not.

Explore the source record for details and available documents.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Combination of vinorelbine plus gemcitabine in previously treated patients with small cell lung cancer: a multicentre phase II study.

PURPOSE: To evaluate the efficacy and toxicity of the gemcitabine plus vinorelbine combination in pretreated patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: Thirty-five pretreated patients (median age 59 years, PS: 0--1 in 97% and 2 in 3%) were treated with gemcitabine (1100 mg/m(2)) and vinorelbine (25mg/m(2)) on d1 and d8 every 3 weeks. Seven (20%) patients were treated with two prior regimens and 20 (57%) were refractory to front-line chemotherapy. RESULTS: In an intention-to-treat analysis two (6%) partial responses (PR) were observed with a duration of 5.6 and 11.1 months. Stable disease (SD) was documented in 8 (23%) patients and progressive disease (PD) in 25 (71%). The overall median survival was 4.5 and the 6 months survival rate was 42.6%. Grades 3--4 neutropenia and thrombocytopenia were observed in 25 and 14% of the patients, respectively. Non-hematological toxicity consisted of grade 2 neurotoxicity occurring in 14% of the patients and grades 2--3 fatigue in 17%. Febrile neutropenia was observed in three (8.6%) patients and one of them died from sepsis. CONCLUSION: The combination of gemcitabine plus vinorelbine cannot be considered as an effective salvage treatment in pretreated patients with SCLC.

Adolescent↗

PubMed2005

Front-line treatment of advanced non-small cell lung cancer with irinotecan and docetaxel: a multicentre phase II study.

PURPOSE: To evaluate the efficacy and tolerance of the irinotecan plus docetaxel combination in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-nine chemotherapy-naïve patients with advanced NSCLC were treated with irinotecan 200mg/m2 followed by docetaxel 80 mg/m2 intravenously on day 1 with granulocyte colony-stimulating factor (150 microg/m2) support from day 2 to 9. Treatment was repeated every 3 weeks. RESULTS: A partial response was achieved in 9 (23%; 95% confidence interval 9.85-36.3%) patients; stable and progressive disease were observed in 10 (25.6%) and 20 (51.4%) patients, respectively. The median duration of response was 7.1 months and the median time to tumor progression 3 months. The median survival time was 10.8 months and the 1-year survival 42.2%. Four (10.3%) patients developed grade 4 neutropenia and all but one were complicated with fever; there was no treatment-related death. Nine (23.1%) patients developed grade 3 or 4 diarrhea while grade 2 or 3 fatigue occurred in nine (23.1%), and grade 3 mucositis in two (2.6%). CONCLUSION: The combination of irinotecan/docetaxel is a relatively active non-platinum-based chemotherapy regimen with manageable toxicity, which could be given in an outpatient basis; this regimen merits to be further studied in order to improve its tolerance and evaluate its clinical relevance in patients who can not tolerate platinum-based doublets.

Adult↗