Résumé
<p><b>OBJECTIVE</b>To compare the efficacy and safety between liposome-paclitaxel plus carboplatin (LPC) and paclitaxel plus carboplatin (PC) as first-line treatment for advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Totally 54 chemotherapy-naive NSCLC patients were equally and randomly assigned into LPC group and PC group. Liposome-paclitaxel was injected on D1 at a dosage of 175 mg/m(2); the same dose and administration with paclitaxel injection in the PC group for a maximum of 2 cycles. The efficacy and adverse reactions after 2 cycles of chemotherapy were compared between these two groups.</p><p><b>RESULTS</b>The overall response rate (CR+PR) was 44.4% in the LPC group and 33.3% in the PC group after 2 cycles of chemotherapy respectively (P=0.577). In the LPC group and PC group, the incidences of myelodepression was 81.5% and 63.0%, respectively (P=0.080), gastrointestinal toxicity was 96.3% and 77.8% respectively (P=0.100), and allergic reactions was 0 and 11.1%, respectively (P=0.000). The median time to progression was 6 months and 5 months, respectively (P=0.420).</p><p><b>CONCLUSION</b>LPC group has the same efficacy with PC group and less adverse reactions than PC group.</p>
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Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Carboplatine , Carcinome pulmonaire non à petites cellules , Traitement médicamenteux , Liposomes , Tumeurs du poumon , Traitement médicamenteux , Paclitaxel , Résultat thérapeutiqueRésumé
<p><b>OBJECTIVE</b>To evaluate the efficacy of erlotinib in patients with metastasis of non-small cell lung cancer who had benefits from initial gefitinib treatment but finally demonstrated resistance, especially in those of unknown EGFR mutation status, and to compare the efficacy of erlotinib between patients who received erlotinib immediately after gefitinib failure and those who received chemotherapy before erlotinib.</p><p><b>METHODS</b>Forty Chinese patients who had been treated with erlotinib (150 mg daily) after gefitinib (250 mg daily) failure were evaluated retrospectively. All of these patients had achieved gefitinib treatment for at least three months with response of partial remission or stable disease. Among them, 16 patients shifted to erlotinib immediately after progression (Group G-E), and the other 24 patients inserted chemotherapy between gefitinib and erlotinib (Group G-C-E).</p><p><b>RESULTS</b>In the whole group, the disease control rate (DCR) of erlotinib was 52.5% (21/40) while the objective response rate (RR) was only 10.0% (4/40). The RR of the group G-E was 6.2% and the group G-C-E was 12.5%, and the DCR was 56.2% and 50.0% in the two groups, respectively, both without significant differences (P = 0.638 and P = 0.755). There was no correlation between the efficacy of erlotinib and that of initial gefitinib in both group G-E and group G-C-E (P = 0.365 and P = 0.658). The median progression-free survival (PFS) and overall survival (OS) for the erlotinib treatment were 3.0 and 12.0 months in the 40 patients. Statistically no significant difference was observed in PFS (4 months in the group G-E and 2 months in the group G-C-E, P = 0.768) and OS (12 months in both Groups, P = 0.510).</p><p><b>CONCLUSIONS</b>Erlotinib can be considered either immediately after gefitinib failure or following the insertion of chemotherapy after gefitinib failure in progressive non-small cell lung cancer patients who initially benefited from gefitinib.</p>
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Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Antinéoplasiques , Utilisations thérapeutiques , Carcinome pulmonaire non à petites cellules , Traitement médicamenteux , Génétique , Anatomopathologie , Survie sans rechute , Chlorhydrate d'erlotinib , Études de suivi , Tumeurs du poumon , Traitement médicamenteux , Génétique , Anatomopathologie , Mutation , Métastase tumorale , Stadification tumorale , Inhibiteurs de protéines kinases , Utilisations thérapeutiques , Quinazolines , Utilisations thérapeutiques , Récepteurs ErbB , Génétique , Induction de rémission , Études rétrospectives , Taux de survieRésumé
<p><b>OBJECTIVE</b>To analyze the association between the EGFR protein level and the EGFR gene mutation status in advanced non-small cell lung cancer (NSCLC), and to explore whether the EGFR protein level is related to the efficacy and survival of the EGFR-TKI drug Gifitinib-treated patients with advanced NSCLC.</p><p><b>METHODS</b>Ninety-nine cases were enrolled in this study. Pathological tissue specimens and paired peripheral blood samples were collected. Exons 19 and 21 of the EGFR gene mutation were detected by direct sequencing. The concentration of plasma EGFR protein was detected by ELISA. Univariate and multivariate statistical analyses of the efficacy and survival were performed using SPSS 13.0 software.</p><p><b>RESULTS</b>The response rate (RR) and clinical benefit rate (CBR) of Gefitinib-treated patients were 51.5% and 79.8%, respectively. There were 35 (35.4%) with positive EGFR gene mutation of the 99 samples. The concentration limit of EGFR protein was 55.42 µg/L. The RR and CBR of patients with EGFR gene mutation was significantly higher than those without mutation (65.7% vs. 43.8%, P = 0.037; 94.3% vs. 71.9%, P = 0.008). The median PFS was prolonged (23 months vs. 10 months, P = 0.014). The CBR of patients with high EGFR protein expression (concentration ≥ 55.42 µg/L) was significantly higher than those with low expression (90.0% vs 64.1%, P = 0.004), and the median PFS was prolonged (21 months vs. 8 months, P = 0.016). EGFR protein level was an independent factor affecting the EGFR gene mutation status. The Correlation between EGFR gene mutation status and EGFR protein level was positive.</p><p><b>CONCLUSIONS</b>Gefitinib is effective in the treatment of advanced NSCLC patients with EGFR gene mutation and high EGFR protein expression. EGFR protein level in peripheral blood may be a molecular biomarker in prediction of efficacy and survival of the Gefitinib treatment in patients with advanced NSCLC.</p>
Sujets)
Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Antinéoplasiques , Utilisations thérapeutiques , Carcinome pulmonaire non à petites cellules , Sang , Traitement médicamenteux , Génétique , Anatomopathologie , Survie sans rechute , Exons , Études de suivi , Tumeurs du poumon , Sang , Traitement médicamenteux , Génétique , Anatomopathologie , Mutation , Stadification tumorale , Quinazolines , Utilisations thérapeutiques , Récepteurs ErbB , Sang , Génétique , Induction de rémission , Taux de survieRésumé
<p><b>OBJECTIVE</b>To explore the clinical factors affecting the sensitivity of EGFR-TKI treatment in advanced non-small cell lung cancer.</p><p><b>METHODS</b>Clinical data were retrospective analyzed to determine the clinical factors affecting the outcome of 166 patients with advanced non-small cell lung cancer who received EGFR-TKI treatment in our hospttal from January of 2005 to December of 2006.</p><p><b>RESULTS</b>One hundred and nineteen patients benefited from EGFR-TKI treatment in the total of 166 patients and the disease control rate was 71.7%. Among the factors analyzed, sex, age, smoking, pathological type, brain and bone metastasis or not when EGFR-TKI was used, the time using EGFR-TKI and the level of LDH at the time of diagnosis had no significant effect on the clinical benefit rate. Among the 126 patients with serum CEA assayed at diagnosis, 84 cases had a higher serum CEA level. Compared with the patients with normal serum CEA level, the patients with a higher serum CEA level benefited more easily from EGFR-TKI therapy, with a disease control rate of 79.8% and 59.5%, respectively (P = 0.016). Among the patients who got benefits from EGFR-TKI treatment, smoking and the CEA level at diagnosis had effects on the duration of progression-free survival. The progression free survivals were 9.57 ± 6.75 months in non-smokers, 4.86 ± 3.44 months in light-smokers and 5.25 ± 4.34 months in heavy-smokers (P = 0.007). The progression free survival was 9.45 ± 7.48 months in the group with a higher serum CEA level and 6.52 ± 4.46 months in the group with normal serum CEA level (P = 0.036).</p><p><b>CONCLUSIONS</b>In patients with advanced non-small cell lung cancer, EGFR-TKIs treatment is safe and effective. The patients with high CEA level are prone to benefit from it.</p>
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Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Antinéoplasiques , Utilisations thérapeutiques , Tumeurs osseuses , Traitement médicamenteux , Tumeurs du cerveau , Traitement médicamenteux , Antigène carcinoembryonnaire , Sang , Carcinome pulmonaire non à petites cellules , Sang , Traitement médicamenteux , Anatomopathologie , Survie sans rechute , Chlorhydrate d'erlotinib , Études de suivi , Tumeurs du poumon , Sang , Traitement médicamenteux , Anatomopathologie , Stadification tumorale , Inhibiteurs de protéines kinases , Utilisations thérapeutiques , Quinazolines , Utilisations thérapeutiques , Récepteurs ErbB , Études rétrospectives , FumerRésumé
<p><b>OBJECTIVE</b>To evaluate the effect of thoracic radiation therapy (TRT) on patients with extensive stage small-cell lung cancer (SCLC).</p><p><b>METHODS</b>One hundred and fifty-four patients with extensive stage SCLC treated in our department between January 2003 and December 2006 were enrolled in this study. Eighty nine patients received chemotherapy and thoracic radiation therapy (ChT/TRT), and 65 patients were treated with chemotherapy alone (ChT without TRT). The chemotherapy was CE (carboplatin and etoposide), PE (cisplatin and etoposide) or CAO (CTX, ADM and VCR) regimens. The total dose of thoracic irradiation was 40-60 Gy with 1.8 - 2.0 Gy per fraction.</p><p><b>RESULTS</b>For the whole group, the median survival time (MST) was 13.7 months, the 2-year and 5-year overall survival rates were 27.9% and 8.1%, respectively. The MST, overall survival rates at 2 years and 5 years in the ChT/TRT group and ChT without TRT group were 17.2 months, 36.0%, 10.1% and 9.3 months, 16.9%, 4.6%, respectively (P = 0.001). The median progression-free survival (PFS) for all patients was 8.0 months, the 2-year and 5-year PFS were 13.6% and 8.2%, respectively. The median PFS, 2-year and 5-year PFS in the ChT/TRT group and ChT without TRT group were 10.0 months, 17.4%, 10.5% and 6.2 months, 9.8%, 4.9%, respectively (P < 0.001). The incidence of intra-thoracic local failure was 29.6% in the ChT/TRT group and 70.0% in the ChT/without TRT group (P = 0.000).</p><p><b>CONCLUSIONS</b>Chemotherapy plus thoracic radiation therapy can improve the overall survival, progress free survival and reduce local regional failure rate in patients with extensive stage SCLC compared with that by chemotherapy alone.</p>
Sujets)
Humains , Protocoles de polychimiothérapie antinéoplasique , Utilisations thérapeutiques , Carboplatine , Utilisations thérapeutiques , Cisplatine , Association thérapeutique , Survie sans rechute , Étoposide , Tumeurs du poumon , Traitement médicamenteux , Radiothérapie , Pronostic , Carcinome pulmonaire à petites cellules , Traitement médicamenteux , Radiothérapie , Taux de survieRésumé
<p><b>OBJECTIVE</b>The aim of this study was to evaluate the efficacy, toxicity and safety of doxorubicin combined with domestically produced docetaxel versus with taxotere, and to investigate whether these two regimens result in similar outcomes in the treatment for non-small-cell lung cancer (NSCLC) patients who failed previous platinum-based chemotherapy.</p><p><b>METHODS</b>Eighty-eight NSCLC patients were enrolled into this clinical phase II trial. The patients randomly received either domestic docetaxel (study arm) or taxotere (control arm) at a dose of 70 mg/m2 on D2, while doxorubicin at a dose of 40 mg/m2 on D1 was administered in both groups. It was repeated every 3 weeks, totally for three cycles. No granulocyte colony-stimulating factor was used to prevent granulocytopenia. The response rate and toxicity were evaluated using World Health Organization toxicity scale and Karnofsky performance status scale.</p><p><b>RESULTS</b>Of the 88 patients, 81 were evaluable in terms of efficacy. There was no complete responder in this series. The response rate (RR) was 17.1% in the study arm versus 7.5% in the control arm, and the clinical benefit rate (CBR) was 80.5% in the study group versus 72.5% in the control group. The most frequent grade 3 or 4 toxicities were neutropenia, leucopenia and gastrointestinal symptoms. Other toxicities such as alopecia and vomiting were mild and generally well tolerated. No fluid retention was noticed.</p><p><b>CONCLUSION</b>The administration of doxorubicin 40 mg/m2 on D1 combined with domestic docetaxel 70 mg/m2 on D2 is proved to be as effective and tolerable as with taxotere. The domestic drug docetaxel may be considered as an alternative for patients with non-small-cell lung cancer who failed previous platinum-based chemotherapy.</p>
Sujets)
Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Protocoles de polychimiothérapie antinéoplasique , Utilisations thérapeutiques , Carcinome pulmonaire non à petites cellules , Traitement médicamenteux , Anatomopathologie , Doxorubicine , Leucopénie , Tumeurs du poumon , Traitement médicamenteux , Anatomopathologie , Stadification tumorale , Neutropénie , Induction de rémission , Thérapie de rattrapage , Taxoïdes , Échec thérapeutique , VomissementRésumé
<p><b>OBJECTIVE</b>To analyze the clinical feature and the value of chemotherapy for advanced stage bronchioloalveolar carcinoma (BAC) of the lung.</p><p><b>METHODS</b>The clinical data of 53 advanced stage BAC patients treated from Jan. 1999 to Dec. 2004 was collected and reviewed. Most of the patients received more than 2 cycles of the combined chemotherapy with platinum-based regimen.</p><p><b>RESULTS</b>Of these 53 eligible patients in this series, 34 (64.2%) were women, 42 (79.2%) never smoked any cigarette, 29 (54.7%) originated from the right lung, and 12 patients (22.6%) showed bilateral multi-lobular or multi-central lesions or diffusive pulmonary involvement. The objective response rate was 17.0% (2 complete response, 7 partial response). 30 (56.6%) patients demonstrated stable disease and 14 (26.4%) patients showed progression of the disease. The median progression-free and overall survivals were 6.1 and 16.0 months, respectively. The 1-year survival rate was 71.7%. Grade 3 or severer toxicities included neutropenia (34.0%), thrombocytopenia (15.1%), anemia (22.6%), nausea and vomiting (39.6%), alopecia (30.2%), constipation (17.0%) and peripheral neurotoxicity (13.2%).</p><p><b>CONCLUSION</b>Advanced bronchioloalveolar carcinoma is likely to occur in woman, nonsmoker and the right lung, frequently with bilateral diffuse pulmonary involvement. The platinum-based combined chemotherapy regimen is modestly effective with tolerable toxicity. Compared with the historical data of lung adenocarcinoma of the same stage, bronchioloalveolar carcinoma has a longer overall survived.</p>
Sujets)
Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Adénocarcinome bronchioloalvéolaire , Traitement médicamenteux , Anatomopathologie , Protocoles de polychimiothérapie antinéoplasique , Utilisations thérapeutiques , Cisplatine , Désoxycytidine , Survie sans rechute , Études de suivi , Tumeurs du poumon , Traitement médicamenteux , Anatomopathologie , Stadification tumorale , Neutropénie , Induction de rémission , Études rétrospectives , Facteurs sexuels , Fumer , VinblastineRésumé
<p><b>OBJECTIVE</b>To investigate the efficacy of combined modality therapy for small cell lung cancer (SCLC) patient with limited stage disease (LD).</p><p><b>METHODS</b>The data of 122 SCLC patients with limited stage disease treated by surgery combined with chemotherapy and radiotherapy were analysed retrospectively.</p><p><b>RESULTS</b>The median survival time (MST) of the 122 patients was 38 months, the 1-, 3-, 5-year survival rate was 83.6%, 50.0% and 38.0%, respectively. If stratified the patients by TNM stage, the MST of stage I was not reached yet, it was 52 months for stage II and 22 months for stage III (P = 0.001); the 5-year survival rate was 57.1%, 43.1% and 28.3%, respectively. For stage III, the MST and 5-year survival rate was 40 months and 45.3% for the patients who received postoperative chemoradiotherapy, and only 20 months and 26.1% for those who were treated with postoperative chemotherapy alone (P = 0.071).</p><p><b>CONCLUSION</b>Combined modality therapy can improve the survival of small cell lung cancer patient with limited stage disease, and TNM stage is still a significant prognostic factor.</p>
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Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mâle , Adulte d'âge moyen , Protocoles de polychimiothérapie antinéoplasique , Utilisations thérapeutiques , Traitement médicamenteux adjuvant , Études de suivi , Tumeurs du poumon , Anatomopathologie , Thérapeutique , Stadification tumorale , Pneumonectomie , Méthodes , Radiothérapie adjuvante , Études rétrospectives , Carcinome pulmonaire à petites cellules , Anatomopathologie , Thérapeutique , Taux de survieRésumé
<p><b>OBJECTIVE</b>To investigate the antitumor efficacy, time to tumor progression (TTP) and toxicity of gefitinib (Iressa, ZD1839)--a selective epidermal growth factor receptor tyrosine kinase inhibitor in the treatment of male patients with advanced non-small-cell lung cancer (NSCLC). Methods Fifty-nine male patients with stage IV NSCLC orally took Iressa 250 mg once daily until disease progression or intolerable toxicity ocurred. They were required to conduct tumor-evaluation before the treatment, one month after Iressa administration and then every other month.</p><p><b>RESULTS</b>Of these 59 patients, no complete regression was observed, 23.7% had partial response (PR), and 16.9% stable disease (SD) with a disease control (PR + SD) rate of 40.7%, while 59.3% had progress of disease (PD). The median time to tumor progression (TTP) was 1.8 months, and the median survival was 8.5 months. Fifty-nine patients were followed up over one year, 35 over two year and 15 over three year, and the 1-, 2- and 3-year survival rates were 42.4%, 17.1% and 13.3%. The most common adverse effects were grade 1 or 2 skin reaction and diarrhea.</p><p><b>CONCLUSION</b>Iressa is effective in antitumor for the male patients with advanced non-small-cell lung cancer, and can improve the survival for those responsing to gefitinib. The adverse effects are usually tolerable.</p>
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Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Humains , Mâle , Adulte d'âge moyen , Antinéoplasiques , Utilisations thérapeutiques , Carcinome pulmonaire non à petites cellules , Traitement médicamenteux , Anatomopathologie , Diarrhée , Évolution de la maladie , Exanthème , Études de suivi , Tumeurs du poumon , Traitement médicamenteux , Anatomopathologie , Stadification tumorale , Quinazolines , Utilisations thérapeutiques , Récepteurs ErbB , Utilisations thérapeutiques , Induction de rémission , Taux de survieRésumé
<p><b>OBJECTIVE</b>To evaluate the efficacy and adverse events of irinotecan (CPT-11) combined with cisplatin (DDP) in the treatment of patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Of 36 NSCLC patients consisting of 23 males and 13 females with a medium age of 52 years included, there were 26 adenocarcinomas, 7 squamous cell carcinomas, 1 adeno-squamous cell carcinoma and 2 unclassified types; 13 stage III B and 23 stage IV; 24 chemonaive and 12 previously treated by chemotherapy with a medium Karnofsky status of 90. All patients had measurable or evaluable parameters. The regimen was administered as following: CPT-11 60 mg/m2, IV, D1, 8 and 15; DDP 80 mg/m2, IV, D1; every 28 days as a cycle.</p><p><b>RESULTS</b>Totally, 97 cycles were carried out in these 36 patients with a medium cycles of 3. Of 35 evaluable patients, 22.9% (8/35) achieved partial response, 60.0% (21/35) had stable disease and 17.1% (6/35) progressive disease. The response rate was 29.2% (7/24) for chemonaive patients and 9.1% (1/11) for these previously treated. The 1-year survival rate was 45.4% with a medium time to tumor progression (TTP) of 199 days for the responders. The incidence rate of grade III/IV adverse events were: 16.7% for neutropenia, 13.9% alopecia, 5.6% diarrhea, 2.8% nausea and vomiting, respectively.</p><p><b>CONCLUSION</b>Irinotecan plus cisplatin is effective with tolerable adverse events in treating patients with advanced non-small cell lung cancer, but further investigation trials are needed.</p>
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Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Alopécie , Protocoles de polychimiothérapie antinéoplasique , Utilisations thérapeutiques , Camptothécine , Carcinome pulmonaire non à petites cellules , Traitement médicamenteux , Mortalité , Anatomopathologie , Cisplatine , Diarrhée , Tumeurs du poumon , Traitement médicamenteux , Mortalité , Anatomopathologie , Stadification tumorale , Neutropénie , Induction de rémission , Taux de survieRésumé
<p><b>OBJECTIVE</b>DNA repair system plays an important role in tumor sensitivity to platinum-based chemotherapy. The purpose of this study was to examine the association between polymorphisms in XRCC1 and XPD, which are involved in DNA repair, and clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>XRCC1 Arg194Trp and XPD Lys751Gln were genotyped by PCR-RFLP method in 200 patients with advanced NSCLC who received platinum-based chemotherapy. Unconditional logistic regression model was used to analyze the association between genetic polymorphisms and clinical responses.</p><p><b>RESULTS</b>The overall response rate (CR + PR) was 36.0%, including 1 CR, 72 PR, 94 SD and 34 PD. The XRCC1 194Trp allele carriers had higher response rate than the subjects with the Arg/Arg genotype (adjusted OR, 2.48; 95% CI, 1.36 - 4.51, P = 0.003). However, the XPD Lys751Gln polymorphism was not found to be associated with the platinum-based chemotherapy. These two genetic polymorphisms may have some interaction in the drug sensitivity, the P value for the trend was significant (P = 0.004).</p><p><b>CONCLUSION</b>Those results suggest that the XRCC1 Arg194Trp and XPD Lys751Gln genetic polymorphisms may be associated with clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer.</p>
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Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Protocoles de polychimiothérapie antinéoplasique , Utilisations thérapeutiques , Carboplatine , Carcinome pulmonaire non à petites cellules , Traitement médicamenteux , Génétique , Cisplatine , Réparation de l'ADN , Génétique , Protéines de liaison à l'ADN , Génétique , Génotype , Tumeurs du poumon , Traitement médicamenteux , Génétique , Paclitaxel , Polymorphisme génétique , Induction de rémission , Vinblastine , Protéine-1 de complémentation croisée de la réparation des lésions induites par les rayons X , Protéine du groupe de complémentation D de Xeroderma pigmentosum , GénétiqueRésumé
<p><b>OBJECTIVE</b>It has been proposed that genetic polymorphisms in apoptosis-related genes might be associated with sensitivity of cancer cells to platinum-based chemotherapy. This study examined the relationship between p53 and p73 genetic polymorphisms and the response to platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>A total of 165 patients with advanced NSCLC treated with platinum-based chemotherapy were genotyped for the p53 codon 72 Pro-->Arg and p73 exon 2 G4C14-->A4T14 polymorphisms using PCR-RFLP and ARMS-PCR assays. Clinical response to the chemotherapy was obtained after 2 to 3 cycles. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model. All statistical tests were two-sided.</p><p><b>RESULTS</b>The p53 Pro allele carriers had higher response rate than non-carriers (OR = 2.46; 95% CI = 1.11 - 5.45). A higher response rate was also observed for the p73 G4C14/A4T14 or A4T14/A4T14 genotype, compared with the G4C14/G4C14 genotype (OR = 2.22; 95% CI = 1.14 - 4.30). When these two polymorphisms were combined to be analyzed, it was found that the response rate in those carrying the wild-type genotypes at both genes was only 7.7%, whereas the response rates in patients carrying 1, 2, or more than 2 variant alleles of p53 and p73 were 34.8%, 42.2% and 40.7%, respectively.</p><p><b>CONCLUSION</b>Those results suggest that p53 and p73 polymorphisms may be associated with clinical responsiveness to platinum-based chemotherapy in advanced NSCLC.</p>
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Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Antinéoplasiques , Utilisations thérapeutiques , Carboplatine , Carcinome pulmonaire non à petites cellules , Traitement médicamenteux , Génétique , Anatomopathologie , Cisplatine , Protéines de liaison à l'ADN , Génétique , Exons , Génotype , Tumeurs du poumon , Traitement médicamenteux , Génétique , Anatomopathologie , Stadification tumorale , Protéines nucléaires , Génétique , Paclitaxel , Polymorphisme génétique , Protéine tumorale p73 , Protéine p53 suppresseur de tumeur , Génétique , Protéines suppresseurs de tumeurs , GénétiqueRésumé
<p><b>OBJECTIVE</b>To evaluate the efficacy, toxicity and safety of an new domestic docetaxel in the treatment of pretreated advanced breast cancer.</p><p><b>METHODS</b>Fourty-four breast cancer patients who had failed in first-line chemotherapy were included in this trial. They received docetaxel as the second-line chemotherapy. Docetaxel was administered alone at a dose of 70 mg/m2 every 3 weeks. The use of granulocyte colony-stimulating factor to prevent granulocytopenia was not permitted. The response rate and toxicity were evaluated by World Health Organization toxicity scale and performance status by Karnofsky scale.</p><p><b>RESULTS</b>Of the 41 evaluable patients, 4 achieved complete response and 14 partial remission, with a response rate and clinical benefit rate of 43.9% and 85.4%, respectively. Grade 3 or grade 4 neutropenia developed in 42.9%, alopecia in 7.1% and vomiting in 4.8% of these patients. Fluid retention was not observed in this series.</p><p><b>CONCLUSION</b>Three-week administration of docetaxel alone at a dose of 70 mg/m2 is effective and tolerable. It provides an alternative for the pretreated advanced breast cancer patients.</p>
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Adolescent , Adulte , Sujet âgé , Femelle , Humains , Adulte d'âge moyen , Alopécie , Antinéoplasiques , Utilisations thérapeutiques , Tumeurs du sein , Traitement médicamenteux , Anatomopathologie , Stadification tumorale , Neutropénie , Induction de rémission , Taxoïdes , Utilisations thérapeutiques , Résultat thérapeutique , VomissementRésumé
<p><b>OBJECTIVE</b>The purpose of this phase I/II study is to investigate the safety/toxicity profile of weekly administration of docetaxel in combination with cisplatin for the chemo-naive patients with advanced non-small cell lung cancer (NSCLC), and to evaluate the efficacy of this regime.</p><p><b>METHODS</b>In phase I trial, 15 patients were included. IV infusion of escalating doses of docetaxel consisting of four levels from 25 to 40 mg/m2 (25, 30, 35, 40 mg/m2) on D1, 8, 15 and cisplatin of 75 mg/m2 on D1 was administered. The regime was repeated every 4 weeks. Blood samples were obtained on D1, 15 in the first cycle to measure the PK. Dose limiting toxicity (DLT) was determined in cycle 1 and defined as any grade 3 non-hematologic toxicity which could not be reverted into grade less than grade 2 within 4 days or any grade 4 hematologic toxicity. Eighty-three patients completed their phase II study with administration of docetaxel at a dose of 35 mg/m2 based on the data of phase I trial.</p><p><b>RESULTS</b>In the phase I trial, grade 3/4 neutropenia was mainly observed in patients who received docetaxel of 40 mg/m2 (level 4) with one patient suffering from an infection signifying dose limiting toxicity (DLT). Non-hematological toxicities including nausea/vomiting, alopecia, fluid retension and asthenia were tolerable. Based on these data, the maximum tolerence dose (MTD) did not reach the level of weekly giving docetaxel at a dose of 40 mg/m2 in combination with cisplatin 75 mg/m2 every 4 weeks. The pharmacokinetic/dynamics results There was no statistically significant difference between clearance value among the 4 dose levels of docetaxel from 25 to 40 mg/m2 when measured by Cmax and AUC. The pharmacokinetics of docetaxel was not influenced by the presence of co-administration of cisplatin when compared D1 with D15 as based on CmaxN, AUCN and CL. In the phase II trial, totally 83 patients received 216 cycles of chemotherapy. One CR (complete response) and 22 PR (partial response) were achieved with an objective response rate of 27.7% in this series and 30.7% in the evaluable patients. The 1-year survival was 48.6% with a median survival of 10.7 months (range: 3-34 months). Hematologic toxicities were the major side effects, though most were mild; grade III/IV neutropenia developed in 15%. The common non-hematologic toxicities were nausea, vomiting and asthenia.</p><p><b>CONCLUSION</b>Weekly consecutive administration of docetaxel on D1, 8, 15 for 3 weeks plus cisplatin on D1 is tolerable and effective with minimal myelosuppression in chemo-naive patients with advanced NSCLC.</p>
Sujets)
Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Protocoles de polychimiothérapie antinéoplasique , Utilisations thérapeutiques , Aire sous la courbe , Carcinome pulmonaire non à petites cellules , Traitement médicamenteux , Anatomopathologie , Cisplatine , Calendrier d'administration des médicaments , Tumeurs du poumon , Traitement médicamenteux , Anatomopathologie , Stadification tumorale , Neutropénie , Induction de rémission , Taux de survie , Taxoïdes , VomissementRésumé
<p><b>OBJECTIVE</b>To evaluate the difference of efficacy, side-effects and quality of life in advanced non-small-cell lung cancer (NSCLC) patients treated with oxaliplatin plus vinorelbine or cisplatin plus vinorelbine.</p><p><b>METHODS</b>Eligible patients were randomly assigned to NL (oxaliplatin + vinorelbine) group and NP (cisplatin + vinorelbine) group in a 2:1 ratio. In the NL group, 70 evaluable cases were treated with oxaliplatin 130 mg/m(2) i.v. on day 2, and vinorelbine 25 mg/m(2) i.v. on days 1 and 8 in 21 days per cycle. In the NP group, 32 evaluable cases were treated with cisplatin 80 mg/m(2) i.v. divided to 2 - 3 days dosing, 21 days per cycle, and vinorelbine administered by the same way as in the NL group. The response rate, time to progression (TTP), one-year survival, side-effects and the quality of life were observed.</p><p><b>RESULTS</b>The response rate was 35.7% vs. 43.8% (P = 0.4), median TTP was 4.7 months vs. 5.5 months (P = 0.6), one-year survival rate was 38.5% vs. 58.6% (P = 0.07) in the NL and NP groups, respectively. Grade I-II neuro-sensory toxicity occurred significantly more frequent in NL group than in NP group (68.4% vs. 36.4%, P = 0.0017). However, Grade I-II granulocytopenia was significantly less occurred in NL group than in NP group (49.4% vs. 70.6%, P = 0.037). There was no statistically difference between the two groups regarding quality of life.</p><p><b>CONCLUSION</b>Due to good efficacy and tolerability, the NL regimen offered a new candidate for treating advanced NSCLC.</p>
Sujets)
Adolescent , Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Protocoles de polychimiothérapie antinéoplasique , Utilisations thérapeutiques , Carcinome pulmonaire non à petites cellules , Traitement médicamenteux , Cisplatine , Calendrier d'administration des médicaments , Tumeurs du poumon , Traitement médicamenteux , Composés organiques du platine , Qualité de vie , Résultat thérapeutique , VinblastineRésumé
<p><b>OBJECTIVE</b>To evaluate the prognostic value of expression of fatty acid synthase (FASE), HER-2/neu, bcl-2 and p53 in stage I non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Expression of FASE, HER-2/neu, bcl-2 and p53 protein was detected by immunohistochemical staining in 84 patients with stage I NSCLC who underwent surgery. Multiple clinical parameters and survival were analyzed.</p><p><b>RESULTS</b>The expression of FASE, HER-2/neu, bcl-2 and p53 was 29.8%, 40.5%, 33.3% and 39.3%, respectively. The local recurrence and bone-metastasis rate were higher in FASE positive patients than in negative patients (28.0% vs 10.2%, P = 0.05; 61.5% vs 23.9%, P = 0.017, respectively). The 5-year survival rate was lower in HER-2/neu and FASE positive patients than in negative patients (37.7% vs 67.7%, P = 0.0083; 35.1% vs 66.1%, P = 0.0079, respectively), which showed that HER-2/neu and FASE expression were associated with significantly poor survival. Patients whose tumors were both HER-2/neu and FASE negative had better outcome, with a 5-year survival rate of 78.2%, compared with 36.3% in those whose tumors were positive for either one (P = 0.002). However, bcl-2 and p53 were not independent prognostic factors for survival.</p><p><b>CONCLUSION</b>HER-2/neu and FASE are independent prognostic factor in stage I non-small cell lung cancer patients who expressed one or both markers.</p>
Sujets)
Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Marqueurs biologiques tumoraux , Métabolisme , Tumeurs osseuses , Carcinome pulmonaire non à petites cellules , Métabolisme , Mortalité , Chirurgie générale , Fatty acid synthases , Métabolisme , Études de suivi , Tumeurs du poumon , Métabolisme , Mortalité , Anatomopathologie , Chirurgie générale , Récidive tumorale locale , Stadification tumorale , Protéines proto-oncogènes c-bcl-2 , Métabolisme , Récepteur ErbB-2 , Métabolisme , Fumer , Taux de survie , Protéine p53 suppresseur de tumeur , MétabolismeRésumé
<p><b>OBJECTIVE</b>To evaluate the antitumor efficacy, time to tumor progression (TTP) and toxicity of Iressa (ZD1839)-a selective epidermal growth factor receptor tyrosine kinase inhibitor in advanced non-small-cell lung cancer (NSCLC) patients who have failed to respond previous chemotherapy.</p><p><b>METHODS</b>Fifty-two patients with grade IV NSCLC previously treated with chemotherapy (77.0% of patients after second line therapy) received 250 mg of Iressa orally once daily until disease progression or development of intolerable toxic reaction. They were required to receive tumor-evaluation before the treatment, one month after Iressa administration and every other month thereafter.</p><p><b>RESULTS</b>Without complete regression being observed, partial response (PR) rate was 21.2% (11/52), stable disease (SD) 32.7% (17/52), disease control rate (PR + SD) 53.8%, progression of disease (PD) 46.2% (24/52); median time to tumor progression (TTP) was 3.5 month. Among them, 22 patients were followed up over one year and the 1-year survival rate was 31.8%. Symptomatic improvement rate was 52.9%. The most common adverse effects were skin reactions and diarrhea which were generally mild (grade 1 or 2). Only one patient withdrew from the trial because of grade III hepatic toxicity with increase in ALT and AST.</p><p><b>CONCLUSION</b>Iressa has significant antitumor activity in advanced NSCLC patients who have previously failed in second or third line chemotherapy. It greatly alleviates tumor related symptoms. Adverse effects are generally tolerable. IRESSA is suitable for patients with poor performance status (ECOG > 2).</p>