Comparison of efficacy and safety between liposome-paclitaxel injection plus carboplatin and paclitaxel plus carboplatin as first line treatment in advanced non-small cell lung cancer.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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). CONCLUSION: LPC group has the same efficacy with PC group and less adverse reactions than PC group.

Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer.

OBJECTIVE: To observe the efficacy and safety of albumin-bound paclitaxel (ABP) monotherapy in treating recurrent advanced non-small-cell lung cancer (NSCLC). METHODS: We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. RESULTS: Of these 21 patients, the best overall response was partial response (PR) in 6 patients (28.6%), stable disease (SD) in 10 patients (47.6%), and progressive disease (PD) in 5 patients (23.8%). The overall response rate (ORR) was 28.6% and the disease control rate (DCR) (PR + SD) was 76.2%. The median progression-free survival (PFS) was 4.0 months (95% CI, 5.0-7.0 months). The main grade 3/4 toxicities included neutropenia (11.1%), peripheral nerve toxicity (5.6%), muscle and joint aches (5.6%), and fatigue (5.6%). CONCLUSIONS: The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.

[Efficacy of erlotinib after the failure of gefitinib in patients with metastasis of non-small cell lung cancer with unknown EGFR mutation status].

OBJECTIVE: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

[Efficacy analysis of third-generation plus platinum doublets in the first-line chemotherapy of advanced non-small cell lung cancer].

OBJECTIVE: To compare the chemotherapeutic efficacies of third-generation plus platinum doublets in advanced non-small cell lung cancer (NSCLC) patients. METHODS: A total of 1112 patients were diagnosed as advanced NSCLC at Chinese Academy of Medical Science and Cancer Hospital from January 2005 to August 2009. Their clinical efficacies and regimen compositions were retrospectively analyzed. All calculations were performed by SPSS 17.0. RESULTS: Differences in objective response rate (ORR) existed among four third-generation agents (paclitaxel, gemcitabine, vinorelbine and docetaxel) plus platinum doublets. Their ORRs were 35.6%, 35.4%, 25.9% and 37.4% respectively (χ(2) = 16.331, P = 0.001). And vinorelbine doublets had the lowest ORR (all P < 0.01). The ORRs of cisplatin and carboplatin doublets were 35.2% and 33.5% respectively. There was no difference in ORR among them (χ(2) = 0.352, P = 0.569). Subgroup analysis showed that the ORRs of four third generation plus platinum doublets were 34.8%, 35.3%, 23.2% and 37.1% in non-agers. And the vinorelbine doublets performed the worst. In the patients with squamous-cell lung cancer, the ORRs of paclitaxel and gemcitabine doublets were 45.5% and 28.4% respectively. And the paclitaxel doublets had the better performance (χ(2) = 5.250, P = 0.026). When combined with carboplatin, the ORRs of four doublets were 36.2%, 16.7%, 15.4% and 32.0% respectively. And the paclitaxel regimen was more effective than the gemcitabine and vinorelbine regimens (P = 0.018 and P = 0.034). The influences of subsequent therapy were nullified when the progression-free survival (PFS) was analyzed. The PFSs of these doublets were (3.67 ± 0.19), (2.95 ± 0.18), (3.05 ± 0.36) and (3.40 ± 0.37) months respectively. There was no difference among them. Pairwise comparisons showed that the mean PFS of patients on paclitaxel doublets was longer than those on gemcitabine doublets. And their PFSs were (3.67 ± 0.19) and (2.95 ± 0.18) months respectively (χ(2) = 7.037, P = 0.008). The PFSs of cisplatin and carboplatin doublets were (3.05 ± 0.14) and (3.65 ± 0.20) months respectively. The patients on carboplatin doublets had a longer PFS than that of those on cisplatin doublets (χ(2) = 6.012, P = 0.014). CONCLUSIONS: No difference exist in ORRs among different third-generation plus platinum doublets. But as the first-line treatment of advanced NSCLC, carboplatin doublets is superior to cisplatin doublets in terms of PFS.

[Association of serum EGFR protein concentration with the efficacy of Gefitinib in the treatment of advanced non-small cell lung cancer].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Thoracic radiation therapy improves the prognosis for patients with extensive stage small-cell lung cancer].

OBJECTIVE: To evaluate the effect of thoracic radiation therapy (TRT) on patients with extensive stage small-cell lung cancer (SCLC). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

[Factors affecting the sensitivity of EGFR-TKI treatment in advanced non-small cell lung cancer].

OBJECTIVE: To explore the clinical factors affecting the sensitivity of EGFR-TKI treatment in advanced non-small cell lung cancer. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

[Analysis of chemotherapeutic efficacy after a failed regimen of epidermal growth factor receptor-tyrosine kinase inhibitor in patients with advanced non-small cell lung carcinoma].

OBJECTIVE: To analyze the treatment efficacy after a failed regimen of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in patients with advanced non-small cell lung carcinoma (NSCLC). METHODS: A retrospective analysis was conducted for 87 patients with advanced NSCLC at our hospital from January of 2005 to December of 2006. All subjects received chemotherapy after a failure of EGFR-TKI, there were 37 cases of male and the median age was 56 ± 11 (range, 31 - 76) years, 50 cases of female, median age 56 ± 13 (range, 31 - 78) years; They received a 2-drug combination chemotherapy (n = 61) and a monodrug chemotherapy (n = 26). The primary endpoint was overall survival (OS). And the secondary endpoints were objective response rate (ORR) and side effects. RESULTS: The OS was 9.4 ± 6.0 (range, 2-33) months and ORR 9.2% (8/87). The OS was 9.1 ± 5.2 (range, 2 - 31) months in combination chemotherapy group and 10.0 ± 7.3 (range, 3 - 33) months in monodrug group; the ORRs were 11.5% (7/61) and 3.8% (1/26) respectively in two groups. There was no significant difference in OS and ORR between two groups (P > 0.05). The common side effects were myelosuppression and nausea/vomiting. The rate of myelosuppression was 87.4% (76/87) and that of 3/4 grade myelosuppression 33.3% (29/87). And the rate of nausea/vomiting was 86.2% (75/87) and that of 3/4 grade nausea/vomiting 10.3% (9/87). Other side effects were mild and well-tolerated. CONCLUSION: If tolerated, chemotherapy after an EGFR-TKI failure may prolong the survival in advanced NSCLC patients.

[A randomized phase II trial of docetaxel and doxorubicin in treatment for patients with non-small-cell lung cancer who have failed previous platinum-based chemotherapy].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Sequential administration of gefitinib and docetaxel as second-line therapy for advanced non-small cell lung cancer: analysis of 82 cases].

OBJECTIVE: To evaluate the efficacy of sequential administration of gefitinib and docetaxel in the second-line therapy for advanced non-small cell lung cancer (NSCLC). METHODS: Eighty-two patients with advanced NSCLC who had received both gefitinib and docetaxel treatment were divided into 2 groups: Group A (n = 17) that were treated with gefitinib first and then crossed over to docetaxel treatment when progressive disease (PD) occurred as second-line treatment, and Group B (n = 65) that were treated with docetaxel first, and then crossed over to gefitinib treatment when PD occurred. RESULTS: The response rate of gefitinib in phase I (duration before crossover) was 27.7%, not significantly different from that in phase II (duration after crossover) (29.4%, P > 0.05). The response rate of docetaxel in phase I was 13.8%, not significantly different from that in phase II (5.9%, P > 0.05). Gefitinib showed an efficacy superior to docetaxel after adjusting the sequence of these two agents (28.0% vs 12.2%, chi2 = 5.46, P = 0.02). The time to progression (TTP) of gefitinib was 6.0 months, significantly longer than that of docetaxol (4.0 months, P = 0.00). Though no statistically significant survival difference was seen between these two groups, stratified analysis showed that the median survival time of the patients with the Eastern Cooperative Oncology Group (ECOG) = 2 in Group A was 13.0 months, significantly longer than that in Group B (6.0 months, P = 0.01). The adverse events (AEs), including skin rash and diarrhea were all generally tolerable. The incidence of AEs was similar in these two groups. CONCLUSION: Although no impact was found in the efficacy and survival between these two different sequential administration of gefitinib and docetaxel for patients with advanced NSCLC, but the patients with poor performance status may get longer survival if they receive treatment of gefitinib first crossed-over to docetaxel.

[Clinical characteristics and chemotherapy of advanced-stage bronchioloalveolar carcinoma of the lung: report of 53 patients].

OBJECTIVE: To analyze the clinical feature and the value of chemotherapy for advanced stage bronchioloalveolar carcinoma (BAC) of the lung. METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

[Gefitinib in the treatment of male patients with advanced non-small-cell lung cancer].

OBJECTIVE: 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. RESULTS: 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. CONCLUSION: 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.

[Combined modality therapy for small cell lung cancer patient with limited stage disease].

OBJECTIVE: To investigate the efficacy of combined modality therapy for small cell lung cancer (SCLC) patient with limited stage disease (LD). METHODS: The data of 122 SCLC patients with limited stage disease treated by surgery combined with chemotherapy and radiotherapy were analysed retrospectively. RESULTS: 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). CONCLUSION: 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.

[Establishment of a model to assess the clinical efficacy of Gefitinib in treatment of non-small cell lung cancer].

OBJECTIVE: To establish a model to predict the clinical response of Gefitinib in non-small cell lung cancer (NSCLC). METHODS: The clinical outcomes of 262 consecutive advanced NSCLC patients to oral treatment of gefitinib 250 mg daily in the past 4 years were reviewed. DNA sequencing was used to detect the mutations in the exons 18, 19, 20, and 21 of the epidermal growth factor receptor (EGFR) tyrosine kinase domain in 55 patients who had enough tumor tissues. RESULTS: The response rate and disease control rate of gefitinib in the advanced NSCLC patients were 30.1% and 78.6% respectively. The median progression free survival and median overall survival were 6.0 and 16.0 months respectively, while the 1, 2 and 3-year survival rates of the NSCLC patients were 60.8%, 35.6%, and 18.3% respectively. The clinical response rate of the patients with EGFR mutation was 50.0%, significantly higher than that of those patients without mutation (16.1%; P = 0.009). In the majority of patients Gefitinib was well tolerated, and the common adverse effects were skin rash and diarrhea. Based on the results of our patients, we try to establish a model which may predict the response of patients by logistic multivariate regression analysis. Patients being female aged under 65, with adenocarcinoma, not smoking, taxone-unresistant and with EGFR mutation were more sensitive to gifitinib. However, COX multivariate regression analysis showed that only the age, histology, smoke status and EGFR mutation were valuable in selection of sensitive patients. So, we set up the cut-off value at 2 in the model based on these 4 factors. The response rate of the patients with 2 or more scores was 34.2%, significantly higher than that of the patients with the scores < 2 (9.3%, P = 0.001). The sensitivity would be doubled when the score increases by one point. CONCLUSION: A simple clinical model based on the patients' age, histology, smoking status and EGFR mutation has been established and is useful to determine the efficacy of gifitinib in NSCLC patients.

[Irinotecan plus cisplatin for the treatment of advanced non-small cell lung cancer].

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[XRCC1 and XPD genetic polymorphisms predict clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer].

OBJECTIVE: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[Association of the responsiveness of advanced non-small cell lung cancer to platinum-based chemotherapy with p53 and p73 polymorphisms].

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: Those results suggest that p53 and p73 polymorphisms may be associated with clinical responsiveness to platinum-based chemotherapy in advanced NSCLC.

[Docetaxel in the treatment of advanced breast cancer ].

OBJECTIVE: To evaluate the efficacy, toxicity and safety of an new domestic docetaxel in the treatment of pretreated advanced breast cancer. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Phase I/II clinical trial of weekly administration of docetaxel plus cisplatin for advanced non-small cell lung cancer].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Efficacy and safety of the combination of paclitaxel and platinum in advanced thymic carcinoma.

This study aimed to assess the efficacy and safety of a combination of paclitaxel and cisplatin/carboplatin for the treatment of advanced thymic carcinoma. Thirty-seven patients (23 men and 14 women, median age 47 years, performance status score ≤2) with pathologically or cytologically diagnosed advanced thymic carcinoma were recruited. Patients received 175 mg/m(2) paclitaxel on day 1 and 75 mg/m(2) cisplatin or 300 mg/m(2) carboplatin on day 2 of a 21 day cycle for at least two cycles to evaluate efficacy and adverse events. No complete response (CR) was observed; 11 patients had a partial response (PR), 16 patients had no change (NC), and 10 had progressive disease, resulting in an overall response rate of 29.7%, a stable rate of 43.2%, and a disease control rate (CR + PR + NC) of 72.9%. Grade I/II and III/IV neutropenia were observed in 21 (56.7%) and 13 (35.1%) patients, respectively. Four (10.8%) patients developed grade I/II thrombocytopenia. Grade I/II and III/IV nausea and vomiting were observed in 19 (51.2%) and five (13.5%) patients, respectively. Grade I/II liver dysfunction was observed in seven (18.9%) patients. Two patients with grade III liver dysfunction recovered after hepatoprotective treatment. The combination of paclitaxel and platinum was effective and well tolerated in patients with advanced thymic carcinoma.