Gemcitabine Plus Cisplatin Group Research Articles

Abstract PO2-06-11: A phase II randomized trial of gemcitabine plus cisplatin(GP) vs gemcitabine plus carboplatin (GC) as the first-line treatment for patients with metastatic triple-negative breast cancer

Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive disease with limited treatment options and poor prognosis. Gemcitabine plus carboplatin (GC) is one of the classic chemotherapeutic regimens for patients with metastatic triple-negative breast cancer(mTNBC) and also a backbone regimen for chemoimmunotherapy, with a median progression-free survival (PFS) of 4.6 months in the first-line (O'Shaughnessy J, et al. J Clin Oncol 2014). Gemcitabine plus cisplatin (GP) has also demonstrated promising efficacy and safety in the first-line phase III trial of mTNBC, with a median PFS of 7.7 months (Hu XC, et al. Lancet Oncol 2015). To further investigate the superiority between carboplatin and cisplatin when combined with gemcitabine, a prospective phase II study was conducted to directly compare the efficacy and safety of GP with GC in the first-line treatment for patients with mTNBC (NCT02341911). Methods: Patients with untreated mTNBC were randomized 1:1 to receive gemcitabine (1250 mg/m2, D1,8) plus cisplatin (75 mg/m2, D1) or gemcitabine (1000mg/m2, D1,8) plus carboplatin (area under the curve 2 mg × min/mL, D1,8) every 21 days until disease progression or intolerable toxicity. The stratification factors included visceral metastasis (yes or no) and the number of metastatic sites (1, 2, or ≥3). The primary endpoint was PFS and secondary endpoints included overall response rate (ORR), overall survival (OS), and safety. Results A total of 150 mTNBC patients were enrolled. After a median follow-up of 49.1 months (IQR 31.3-70.7), PFS events had been recorded in 55 (73.3%) of 75 patients in the GP group and 59 (78.7%) of 75 patients in the GC group. PFS was numerically longer in the GP group than in the GC group, though not significantly (median, 7.8 months [95% CI 7.2–8.4] vs. 6.9 months [95% CI 6.4–7.4]; HR, 0.93; 95% CI 0.64–1.34; P = 0.689; stratified HR, 0.84; 95% CI 0.58–1.23; P = 0.375). Median OS was 20.7 months (95%CI 17.9-23.5) in GP group and 20.9 months (95%CI 15.3-26.5) in GC group, HR, 1.13; 95% CI 0.77–1.67; P = 0.537; stratified HR, 1.03; 95% CI 0.70–1.52; P = 0.886). The ORR of GP and GC was 49.3% and 41.3% in the intent-to-treat population. Dose reduction occurred in 30(40.0%) patients in the GP group and 38 (50.7%) patients in the GC group. Grade 3 and 4 hematological AEs, including leucopenia, neutropenia, anemia, and thrombocytopenia were slightly higher in the GC group. Grade 3 and 4 non-hematological AEs, including nausea, vomiting, and hearing toxicity, were more common in the GP group. No treatment-related deaths were reported. Conclusions Cisplatin was not associated with a survival advantage over carboplatin when combined with gemcitabine as a first-line treatment for patients with mTNBC, though numerically longer PFS and higher ORR was observed. The safety profiles of the two combinations were different but the adverse events were manageable. Citation Format: Chengcheng Gong, Yannan Zhao, Leiping Wang, Jun Cao, Zhonghua Tao, Ting Li, Mingchuan Zhao, Haitao Miao, Juan Jin, Xichun Hu, Biyun Wang. A phase II randomized trial of gemcitabine plus cisplatin(GP) vs gemcitabine plus carboplatin (GC) as the first-line treatment for patients with metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-06-11.

Prolonged progression-free survival achieved by gemcitabine, cisplatin, and albumin-bound paclitaxel for the treatment of advanced biliary tract cancers.

A regimen of gemcitabine, cisplatin, and nab-paclitaxel (GPA) has shown promising results in patients with advanced biliary tract cancer (aBTC). This study aimed to evaluate the benefit of GPA compared to a regimen of gemcitabine plus cisplatin (GP) in patients with aBTC. Retrospective study. Patients with aBTC who received first-line chemotherapy with GPA or GP regimen at the Samsung Medical Center between July 2020 and June 2022 were included. The primary endpoint was progression-free survival (PFS). In all, 37 patients were treated with GPA and 43 patients with GP. The GPA group showed significantly longer median PFS [12.0 months (95% CI, 7.2-16.8)] compared to the GP group [5.5 months (95% CI, 3.7-7.4; p = 0.007)]. The median overall survival (OS) was also longer in the GPA group [18.7 months (95% CI, 13.7-23.7)] than in the GP group [10.7 months (95% CI, 1.5-19.9); p = 0.021]. First-line chemotherapy with GPA was associated with longer PFS, while metastatic disease at initial diagnosis and post-treatment increase in CA 19-9 level were associated with worse PFS. The GPA regimen improved the PFS of patients with aBTC compared to the GP regimen but showed no significant benefit in terms of OS after adjusting for confounding variables. Further large-scale studies are required to establish optimal indications for GPA.

A multicenter, open-label, randomized phase II study evaluating adjuvant gemcitabine plus cisplatin (GC) and capecitabine with concurrent capecitabine radiotherapy (CAPE-RT) in patients with operated gallbladder adenocarcinoma (GBC): The GECCOR-GB trial.

4017 Background: Adjuvant gemcitabine plus cisplatin (GC) and concurrent chemo-radiotherapy are commonly used treatment options for resected GBC. Methods: GB-GECCOR is a multicentre, open-label randomized non-comparative phase II study in patients of Gallbladder cancer (GBC), with R0 or R1 resection within 3 months of randomization. Patients were randomized 1:1 to GC arm (Gem 1000 mg/m2 and Cisplatin 25mg/m2 on day 1 and 8, q 3 weeks) for 6 cycles or CAPE-RT arm {Capecitabine 1000mg/m2 BD on days 1-14, q 3 weeks for 2-4 cycles followed by chemoradiation (RT: 45 Gy over 25 fractions concurrent with capecitabine: 825mg/m2 twice) followed by 2-4 cycles of capecitabine for a total of 6 cycles}. The primary end point was 1-year disease-free survival (DFS). With 80% power to detect the difference between a 59% (minimum sufficient activity of the regimen) and a 77% (sufficient activity for future larger studies with the regimen) 1-year DFS rate assuming an attrition of 10%, a total of 90 patients were required for the study. Results: Between May 2019 and February 2022, 90 patients (45 in each arm), were included. Stage II and stage III GBC were seen in 50 (56%) and 40 patients (44%) respectively, with R0 resection observed in 86 patients (96%). Patient characteristics were well balanced between the 2 arms except for R1 resections which were greater in the CAPE-RT arm (p=0.041). With a median follow-up duration of 23 months, the 1-year DFS rate was 88.9% (95% CI: 79.5-98.3) in the GC group and 77.8% (95% CI: 65.4 – 90.2) in the CAPE-RT group, respectively. The most common AEs were grade 3/4 neutropenia in 6 patients (13.3%) in the GC group and grade 2/3 HFS in 14 patients (31.1.%) in the CAPE-RT group. The distant metastases were seen in 12 patients (26.6 %) in each arm and loco-regional metastases in 3 patients (6.6 %) in the GC arm. Conclusions: In this study of operated GBC, GC and CAPE-RT successfully achieved the minimum pre-specified DFS rates. Within the confines of a non-comparative randomised study, GC had narrowed the gap in survivals of stage III vs. stage II GBCs, which was not noted in the CAPE-RT arm. This study results give credence to the use of both regimens as reasonable standards of care till evaluation in larger phase 3 studies. Clinical trial information: CTRI/2019/05/019323 . [Table: see text]

Comparison Efficacy and Safety of Gemcitabine plus Cisplatin and 5-Fluorouracil plus Cisplatin for Metastatic Nasopharyngeal Carcinoma: A Meta-Analysis and Systematic Review.

Objective To compare the efficacy and safety of gemcitabine plus cisplatin (GP) and 5-fluorouracil plus cisplatin (PF) for metastatic nasopharyngeal carcinoma. Methods The clinical trials of GP and PF in the treatment of metastatic nasopharyngeal carcinoma (NPC) were searched in PubMed, EMBASE, Cochrane Library, and Web of Science. The literature search met the inclusion and exclusion criteria. The software Revman 5.4 was used for data analysis, and STATA 15.0 was used for publication bias. Results 10 studies were included in this meta-analysis. The results showed that the GP group had a higher clinical remission rate than the PF group (RR = 1.22, 95% CI (1.03–1.44), P=0.02, P=0.02). GP and PF groups in OS, PFS, and DMFS had the same effect at 1, 2, and 3 years (OS at 1 year: RR = 1.04, 95% CI (0.95–1.15), P=0.37, P=0.37; 2 years: RR = 1.08, 95% CI (0.94 1.23), P=0.28, P=0.28; 3 years: RR = 1.07, 95% CI (0.89 1.29), P=0.46; PFS at 1 year: RR = 1.98, 95% CI (0.29 13.44), P=0.49; 2 years: RR = 3.09, 95% CI (0.10 97.55), P=0.52; 3 years: RR = 0.95, 95% CI (0.73 1.24), P=0.71; DMFS at 1 year: RR = 1.01, 95% CI (0.90–1.14), P=0.83; 3 years: RR = 1.10, 95% CI (0.85–1.41), P=0.47. The number of hematological adverse reactions occurred in GP group was higher than the PF group. Conclusion The GP and PF groups had similar OS, PFS, and DMFS, but the GP group had a higher clinical remission rate. Therefore, GP may be the first choice for metastatic NPC.

Response to Pembrolizumab After Dose-Reduced Cisplatin Plus Gemcitabine Chemotherapy Is Inferior to That After Carboplatin Plus Gemcitabine Chemotherapy in Cisplatin-Unfit Patients With Advanced Urothelial Carcinoma.

Response to pembrolizumab after first-line chemotherapy is vital to prolonged survival in advanced, unresectable, and/or metastatic urothelial carcinoma (aUC). However, there are sparse clinical data on host-tumor immune modification by first-line platinum-based chemotherapy. This study investigated the association between response to first-line gemcitabine plus cisplatin (GC) or carboplatin (GCarbo) chemotherapy and response to subsequent pembrolizumab treatment. A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 108 patients who received first-line GC or GCarbo followed by second-line or later pembrolizumab were eligible for investigation and were classified into 3 groups: 48 receiving full-dose GC, 21 receiving dose-reduced GC, and 39 receiving GCarbo. Overall survival (OS) was calculated using the Kaplan-Meier method and compared using the log-rank test. Possible factors associated with the response to pembrolizumab were evaluated using binary logistic regression methods. The rate of patients undergoing surgical removal of the primary organ was higher and creatinine clearance was lower in the dose-reduced GC and GCarbo groups than in the full-dose GC groups. Pembrolizumab responders had significantly better survival benefits than nonresponders. The rate of pembrolizumab responders was much higher in first-line chemotherapy responders than in first-line chemotherapy nonresponders. In contrast to the full-dose GC and GCarbo groups, the pembrolizumab responder rate was lower, and no association was observed between response to first-line chemotherapy and response to pembrolizumab in the dose-reduced GC group. Cisplatin and carboplatin may play an important role in the antitumor immune response, which could impact the outcome of subsequent pembrolizumab treatment. Given that the rate of response to pembrolizumab after dose-reduced GC chemotherapy was relatively low, this regimen is not recommended for cis-unfit patients with aUC. Further studies are required to understand the mechanisms responsible for the cross-reactivity of platinum and immune checkpoint inhibitors.

Gemcitabine Versus Docetaxel Plus Cisplatin as Induction Chemotherapy in Nasopharyngeal Carcinoma.

To compare tumor volume reduction after induction chemotherapy (IC) with gemcitabine plus cisplatin (GP) and docetaxel plus cisplatin (DP) and to evaluate the influence on subsequent radiotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC). Retrospective clinical study. Patients who received GP or DP IC followed by concurrent chemoradiotherapy (CCRT) were retrospectively enrolled. Propensity score matching (PSM) was adopted to control the balance between the GP and DP groups. A total of 41 patients treated with GP and 53 patients treated with DP were enrolled. After matching, 33 sub-pairs of 66 patients were generated in the post-PSM cohort. As compared with DP, GP was superior in its gross tumor volume of the nasopharynx (GTVnx) reduction (28.88% vs. 18.73%; P=.014) but equivalent in its gross tumor volume of the lymph nodes (GTVnd) reduction (37.58% vs. 29.79%; P=.229). Univariate and multivariate analyses confirmed that the chemotherapy regimen was an independent factor associated with the reduction in GTVnx (P=.011). The GP group exhibited advantages in the dosimetric parameters of the planning target volume of high-risk volume and low-risk volume (PTV1 and PTV2), lenses, temporal lobes, and parotid glands. Univariate and multivariate analyses confirmed that chemotherapy regimen was an independent factor associated with the dosimetric parameters of PTV1, PTV2, lenses, temporal lobes, and parotid glands. GP regimen achieves a greater GTVnx reduction than DP regimen and has an advantage in the dosimetry of subsequent CCRT. 3 Laryngoscope, 132:2379-2387, 2022.

Efficacy and Feasibility of Adjuvant Gemcitabine Plus Cisplatin Chemotherapy After Major Hepatectomy for Biliary Tract Cancer

The efficacy and feasibility of gemcitabine plus cisplatin (GC) chemotherapy in an adjuvant setting is unclear in patients with biliary tract cancer (BTC) undergoing major hepatectomy. Patients with BTC who underwent major hepatectomy between 2008 and 2018 were included. Patients who received adjuvant chemotherapy (AC) were then divided into two groups: a GC group and a gemcitabine (GEM) alone group. AC-related factors and patient outcomes were investigated. Fifty (GC: 28, GEM: 22) patients received AC, and 33 patients did not. No difference in completion rate, relative dose intensity, or adverse events was seen between the two AC groups. Multivariate analysis revealed that AC with GC was an independent predictor of improved survival and reduction of early recurrence. AC with GC is tolerable and associated with better outcomes in patients with BTC who have undergone major hepatectomy.

Comparison of efficacy and safety of three induction chemotherapy regimens with gemcitabine plus cisplatin (GP), cisplatin plus fluorouracil (PF) and cisplatin plus capecitabine (PX) for locoregionally advanced previously untreated nasopharyngeal carcinoma: A pooled analysis of two prospective studies.

We compared, in this pooled analysis, the differences in efficacy and safety between three induction chemotherapy regimens including gemcitabine plus cisplatin (GP), cisplatin plus fluorouracil (PF) and cisplatin plus capecitabine (PX) in patients recruited into our two prospective studies for previously untreated locoregionally advanced nasopharyngeal carcinoma (NPC). GP, PF or PX followed by radical concurrent chemoradiotherapy was given to patients with previously untreated locoregionally advanced (stage III to IVA) NPC prospectively recruited into our two prospective studies. The study endpoints included progression-free survival (PFS) and overall survival (OS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and major acute and late treatment-related toxicities (grade≥3). From 2006 to 2016, 278 patients were enrolled (84, 94 and 100 patients in GP, PF and PX group respectively). After a median follow-up of 80months, the 3-year PFS, OS, LRFS, DMFS and CSS of the whole population were 78.7%, 88.1%, 84.9%, 80.9% and 89.8%, respectively. There were no significant differences in prespecified survival endpoints among GP, PF and PX in both stage III and stage IVA patients. GP had lower incidences of severe (grade≥3) anemia and diarrhea in stage III patients, as well as severe anemia, dehydration, renal impairment and vomiting in stage IVA patients. The incidences of grade≥3 late toxicities were similar among these 3 induction regimens. GP had similar efficacy and potentially fewer treatment-related complications compared with PF and PX as induction chemotherapy for previously untreated locoregionally advanced NPC.

Comparison of Gemcitabine Plus Cisplatin vs. Docetaxel Plus Fluorouracil Plus Cisplatin Palliative Chemotherapy for Metastatic Nasopharyngeal Carcinoma.

Objective: Our study aimed to compare the efficacy and toxicity of two chemotherapy regimens, gemcitabine plus cisplatin (GP) vs. docetaxel plus, fluorouracil plus cisplatin (TPF), in metastatic nasopharyngeal carcinoma (NPC) patients.Methods: We retrospectively enrolled metastatic NPC patients between July 2006 and December 2016 who were treated with TPF or GP palliative chemotherapy (PCT). The association between the PCT regimens and survival conditions was evaluated by log-rank tests and the Cox proportional hazards model. A cohort was created using propensity score matching with the ratio of 1:1 to clarify the results of the multivariable Cox regression analyses. Overall survival (OS) was the primary endpoint.Results: Of 266 eligible patients, 186 and 80 patients, respectively, received TPF and GP regimen. No significant difference was demonstrated in the survival rate between the GP and TPF groups (3-year OS: 52.6 vs. 50.3%; P = 0.929). However, multivariable analysis suggested receiving GP as an independent protective factor (hazard ratio, 0.864; 95% confidence interval, 0.753–0.992; P = 0.042). In the matched cohort, treatment with GP was also associated with a significantly higher OS (3-year OS: 52.6 vs. 35.6%, P = 0.042). Subgroup analysis indicated that the superiority of GP reflected in patients with secondary metastases rather than primary metastases. The incidence of grade 3 to 4 treatment-related toxicity was more common in the TPF group than in the GP group.Conclusion: Our study suggested that GP might be superior to TPF for metastatic NPC patients, especially those with secondary distant metastases. Further studies are necessary to validate our results.

Comparing Long-Term Survival and Late Toxicities of Different Sequential Chemotherapy Regimens with Intensity-Modulated Radiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma

OBJECTIVES: To evaluate long-term survival outcomes and late toxicities of the sequential chemotherapy regimen of gemcitabine plus cisplatin (GP) compared with cisplatin plus fluorouracil (PF) in locoregionally advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From June 2005 to December 2014, 235 patients with pathologically confirmed NPC treated with intensity-modulated radiotherapy (IMRT) combined with GP (n = 144) or PF (n = 91) were retrospectively analyzed. RESULTS: After a median follow-up of 61 months, the 5-year overall survival (OS) rates were not significantly different between GP and PF groups (84.2% vs. 74.4%, P = .208). The 5-year local control rates were significantly improved in the GP group (96.3% vs 84.1%, P = .010). Subgroup analysis demonstrated that the increased benefits of GP were from T1-3 classification (99% vs. 87.8%, P = .013) and stage III patients (100% vs. 82.4%, P = .017). The most common late adverse events were xerostomia and hearing impairment. The incidences of grade 3 to 4 late toxicities were relatively low and were similar in the two groups. CONCLUSIONS: Sequential chemotherapy combined with IMRT achieved satisfactory survival outcomes in locoregionally advanced NPC with acceptable late toxicities. The GP regimen significantly improved local control compared with PF regimen. Further phase III randomized clinical studies were warranted.

Gemcitabine Plus Cisplatin Chemotherapy Prolongs the Survival in Advanced Hilar Cholangiocarcinoma: A Large Multicenter Study.

Gemcitabine plus cisplatin (GC) is recommended as first-line treatment for advanced cholangiocarcinoma. We investigated the impact of GC in patients with unresectable hilar cholangiocarcinoma (HC) based on the time taken for effective biliary drainage (EBD). We retrospectively enrolled 113 patients with unresectable HC. Thirty-nine and 74 patients received GC chemotherapy and best supportive care (BSC), respectively. EBD was defined as a reduction in total bilirubin >50% or to a value <2 mg/dL after the drainage procedure. Early EBD (eEBD) and delayed EBD (dEBD) were separated by 2 weeks. Overall survival (OS) was estimated. The GC group showed a significantly longer median OS than the BSC group (12.8 vs. 6.1 mo; P<0.001). Moreover, the eEBD group experienced a significantly longer OS than the dEBD group (8.2 vs. 4.3 mo; P<0.001). GC led to improved OS in the eEBD (12.8 vs. 6.8 mo; P=0.003) and dEBD (12.2 vs. 3.4 mo; P=0.009) groups. In multivariate analysis, dEBD (adjusted hazard ratio [aHR], 1.785; 95% confidence interval [CI], 1.183-2.691; P=0.006), BSC (aHR, 2.409; 95% CI, 1.579-3.675; P<0.001), and an ECOG status ≥2 (aHR, 3.721; 95% CI, 2.093-6.615; P<0.001) were associated with poor prognosis. In GC group, the older (70 y and above) patients did not have a higher risk of death than younger patients. GC prolongs the survival of patients with unresectable HC, even those with dEBD or elderly.

Impact on gemcitabine plus cisplatin in unresectable hilar cholangiocarcinoma patients according to effective biliary drainage: A multicenter study.

e15658 Background: Hilar cholangiocarcinoma (HC) is known to have a poor prognosis due to cholangitis and lack of effective chemotherapeutic regimen. Since 2010, gemcitabine plus cisplatin (GP) is recommended as first-line chemotherapy in cholangiocarcinoma. However, it is still unclear whether GP is effective on HC. We aimed to evaluate the impact on GP in unresectable HC patients according to effective biliary drainage (EBD). Methods: From 2010 to 2016, 112 patients with unresectable HC confirmed by biopsy at three tertiary referral hospitals in Korea were enrolled. 38 patients received GP [cisplatin (25 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter), each administered on days 1 and 8, every 3 weeks]. 74 patients received best supportive care (BSC). The EBD group was defined as a total bilirubin decrease of less than 2 mg/dl within 2 weeks after the first drainage procedure or 50% reduction than pre-procedure total bilirubin. Overall survival (OS) was evaluated in GP group and BSC group according to EBD achieved using the Kaplan–Meier survival curve and the log-rank test. Results: When compared with the BSC group (n = 74), the GP group (n = 38) obtained a benefit in OS (median OS, 6.14 vs 12.7 months, p &lt; 0.001). Moreover, patients with EBD experienced significantly longer OS compared with ineffective biliary drainage (IEBD) patients (median OS, 8.03 vs 5.01 months, p &lt; 0.005). GP chemotherapy was beneficial for OS in IEBD group (p &lt; 0.001) as well as in EBD group (p &lt; 0.005). In the multivariate analysis, GP chemotherapy (HR 0.33, 95% CI 0.21–0.52, p &lt; 0.001), EBD (HR 0.60, 95% CI 0.40–0.91, p &lt; 0.001) and 2 more metastatic site (HR 3.21, 95% CI 1.66–6.18, p &lt; 0.001) were significant prognostic factors. Conclusions: GP chemotherapy provides longer survival in HC, regardless of effective or ineffective biliary drainage.

P3.01-115 Liposomal Paclitaxel Versus Gemcitabine: Which is Better?

Lung cancer tends to metastasize to lymph nodes in the early stage.The liposomal Paclitaxel(LP) injection has less side effects and higher uptake.It is also characterized as being able to target to organs with rich reticuloendothelial system and keeping a high concentration for a long time. We assume that LP injection has a better curative effect against NSCLC with regional lymph node metastasis. Patients divide to 58 for LP and 56 for Gemcitabine plus cisplatin (GP).Those patients have good comparability in gender,age,ECOG points,pathological pattern,TNM staging and chemotherapy cycles.21 days as a single cycle, each patient finished at least 2 cycles. Estimation was carried on within one week when they have finished the chemotherapy. Chemotherapy Continues if the result turns out CR+PR+SD. surgical treatment would be suggested if the stage of cancer decreases and the lesions of NSCLC turn technically removable. Then continue chemotherapy after surgery, 4 to 6 cycles in total. The alleviation rate of lymph nodes metastasis in LP group is significantly higher.The disease control rate of lymph nodes metastasis is 96.551% vs. 92.857%, p=0.38.The alleviation rate of squamous cell carcinoma and the disease control rate is not statistically significant. The alleviation and disease control rate of primary tumor in LP and GP group does not have statistical significance.And among LA patients,it the same trend. The LP group has a longer period without disease progression and a higher survival rate in 1 year than the GPgroup.The medium PFS of squamous cell carcinoma in 5 LP group is 8 months which is higher than that in GP group (5.5 months) but does not have statistical significance. The survival rate in 1 year of squamous cell is 50% (16/32). The PFS of IIIB stage in LP group is 10 months, significantly higher than GP group(4 months),survival rate in 1 year in LP group is also higher but is not statistically significant. As to side effect, the LP group is significantly lower in the incidence of thrombocytopenia, granulocytopenia, anemia and white blood cell reduction.However, the LP group is higher incidence of alopecia. Chemotherapy with LP has higher alleviation rate than chemotherapy with GP in treating advanced NSCLC with regional lymph node metastasis, especially for squamous cell carcinoma. The survival rate and PFS in stage IIIB/IV of LP is also higher than that of GP. Meanwhile, LP is able to reduce the incidence rate of side effects such as hrombocytopenia, granulocytopenia,anemia, white blood cell reduction, nausea and vomiting.

Bevacizumab plus chemotherapy for patients with advanced pulmonary adenocarcinoma harboring EGFR mutations

PurposeEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and bevacizumab plus chemotherapy were effective for EGFR-mutant patients. However, the appropriated treatment orders remained controvertible. We investigated the efficacy of treatment orders between bevacizumab plus chemotherapy and EGFR-TKIs for EGFR-mutant patients with advanced pulmonary adenocarcinoma.Patients and methodsThis study involved 40 EGFR-mutant patients with advanced pulmonary adenocarcinoma who were treated with bevacizumab plus carboplatin and paclitaxel (Bev + CP) and EGFR-TKIs in different treatment orders or gemcitabine plus cisplatin (GP) in first-line setting. Seventeen patients were treated with Bev + CP and 10 cases with GP in first-line treatment. Thirteen patients received EGFR-TKIs after first-line Bev + CP regimen, while 13 patients were treated with first-line EGFR-TKIs. Progression-free survival (PFS), the response rate (ORR) and overall survival (OS) were evaluated.ResultsMedian PFS of Bev + CP treatment was significantly longer in first-line than non-first-line settings (11.7 vs. 5.6 months, P = 0.003). Median OS was 37.8 months for EGFR-mutant patients with first-line Bev + CP followed by second-line EGFR-TKIs and 31.0 months for those with first-line EGFR-TKIs and non-first-line Bev + CP, respectively (P = 0.509). Median PFS was 11.7 (95% CI 10.6–12.8) months for Bev + CP group and 4.7 (95% CI 4.4–5.0) months for GP group with the hazard ratio of 0.17 (P = 0.001). ORR was 70.6 and 50.0% in the two groups, respectively (P = 0.415). However, there was no significant difference in median OS (33.7 vs 27.8 months, P = 0.293).ConclusionsFirst-line Bev + CP followed by EGFR-TKIs might possibly provide favorable prognosis for EGFR-mutant patients. Bev + CP regimen significantly prolonged PFS in first-line than non-first-line settings. These findings warrant further investigations.

Clinical research of drug-resistant gene detection combined with adenosine triphosphate-tumor chemosensitivity assay for guiding the second-line chemotherapy of lung squamous cell cancer

Objective To investigate the significance of resistant gene detection combined with adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in the second-line chemotherapy of lung squamous cell cancer, and to provide a reference for clinical treatment. Methods 150 patients with lung squamous cell cancer diagnosed by histopathology or cytology and with the disease progressed after NP regime chemotherapy were enrolled. The mRNA expressions of excision repair cross complementation 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) were detected by RT-PCR, and ATP-TCA was carried out. After detected by RT-PCR and ATP-TCA, the patients who were sensitive to gemcitabine plus cisplatin (GP) accepted the second-line systemic chemotherapy with GP regimen, and the others who were not sensitive to GP regimen or whose results of gene detection and ATP-TCA were on the contrary took the second-line chemotherapy regimens with docetaxel plus cisplatin (DP). Both groups accepted 2-4 cycles of systemic chemotherapy. The chest CT was followed up, and the response rate (RR), progression-free survival (PFS) and median survival time (MST) were investigated. Results The RR of GP group was 36.2 % (17/47), while the DP group was 28.1 % (26/92), and the difference was statistically significant (χ2 = 4.274, P 0.05). Conclusion The resistance gene detection combined with ATP-TCA have certain guiding significance on the second-line chemotherapy for advanced lung squamous cell cancer. Key words: Lung neoplasms; Carcinoma, squamous cell; Excision repair cross complementation 1; Ribonucleotide reductase M1; Adenosine triphosphate-tumor chemosensitivity assay; Second-line chemotherapy

Tailored Selection of First-Line Cisplatin-Based Chemotherapy in Patients with Metastatic Urothelial Carcinoma of Bladder

Purpose: Methotrexate, vinblastine, doxorubicin plus cisplatin (MVAC) and gemcitabine plus cisplatin (GC) are both effective first-line chemotherapy. We explore the responsive variables of MVAC and GC for patients with metastatic urothelial carcinoma of bladder (mUCB).Materials and Methods: Patients who were initially diagnosed to have mUCB and received MVAC or GC as metastatic first-line chemotherapy between 2000 and 2014 at Kaohsiung Chang Gung Memorial Hospital were reviewed. Totally, 130 patients were enrolled into our study. Univariable Cox proportional hazard models were constructed for OS. Hazard ratio (HR) and 95% confidence intervals (CIs) was also presented.Results: There were 50 patients (38%) in the MVAC group and 80 patients (62%) in the GC group. The median OS was insignificantly different between MVAC and GC groups, accounting for 17.0 and 14.4 months (P = 0.214), respectively. OS of MVAC group was significantly longer with regard to age ≦ 60 years (HR: 0.38, 95% CI: 0.12-0.97, P = 0.036), pure urothelial carcinoma (HR: 0.56, 95% CI: 0.34-0.90, P = 0.015), > 1 metastatic sites (HR: 0.19, 95% CI: 0.08-0.44, P = < 0.001), and neutrophil to lymphocyte ratio > 3(HR: 0.45, 95% CI: 0.25-0.81, P = 0.006), while OS with GC group was significantly longer with regard to variant urothelial carcinoma (HR: 0.56, 95% CI: 0.34-0.90, P = 0.015).Conclusions: Our study disclosed the predictive factors of different regimen for mUCB. These results have clinical implication for physicians who treat patients with mUCB.

Sequential Cytokine-Induced Killer Cell Immunotherapy Enhances the Efficacy of the Gemcitabine Plus Cisplatin Chemotherapy Regimen for Metastatic Nasopharyngeal Carcinoma

In this study, we investigated the efficacy of sequential cytokine-induced killer cell (CIK) immunotherapy with gemcitabine plus cisplatin (GC) regimen chemotherapy in metastatic nasopharyngeal carcinoma (NPC) patients. Between September 2006 and April 2010, 222 NPC patients with distant metastasis after radiotherapy completion were retrospectively analyzed: 112 patients received 4–6 cycles of GC chemotherapy at 4-week intervals, followed by at least 4 cycles of CIK immunotherapy at 2-week intervals (GC+CIK group); the remaining 110 patients received 4–6 cycles of GC chemotherapy alone (GC group). The evaluation of long-term efficacy showed that the progression-free survival (PFS) rate was significantly higher in the GC+CIK group (log-rank test; p = 0.009), as was the overall survival (OS) rate (p = 0.006). In conclusion, sequential CIK treatment may be effective in enhancing the therapeutic efficacy of GC chemotherapy for metastatic NPC patients. This study provides a basis for alternative therapeutic strategies for metastatic NPC.

Gemcitabine plus Cisplatin versus Capecitabine plus Cisplatin as First-Line Chemotherapy for Advanced Biliary Tract Cancer: A Retrospective Cohort Study

Background and Aim: Gemcitabine plus cisplatin (GP) is a standard chemotherapy option for patients with advanced biliary tract cancer (BTC). We compared the efficacy and safety of capecitabine plus cisplatin (XP) versus GP in advanced BTC. Methods: The records of all patients treated with GP or XP chemotherapy for unresectable, metastatic, or recurrent BTC at the National Cancer Center between December 2001 and August 2012 were reviewed retrospectively. Patients with histologically confirmed intrahepatic cholangiocarcinoma, gallbladder cancer, or extrahepatic cholangiocarcinoma were enrolled. Results: Of the 344 patients enrolled, 127 received GP and 217 received XP. At a median follow-up time of 8.9 months, the median time to progression was longer in the GP group than in the XP group (5.6 vs. 4.7 months), but the difference was not statistically significant (p = 0.081). The median overall survival (OS) was 8.4 months (95% CI 6.2-10.7) in the GP group and 7.6 months (95% CI 6.8-8.7) in the XP group (p = 0.024), with statistical significance retained following multivariate analysis (HR 0.72; 95% CI 0.527-0.987; p = 0.004). Grade 3/4 toxicities were significantly more frequent in the GP group than in the XP group (40.9 vs. 24.9%, p = 0.002). Conclusions: GP was superior to XP in prolonging OS, despite increasing the rate of grade 3/4 adverse events.

Impact of EGFR tyrosine kinase inhibitors versus chemotherapy on the development of leptomeningeal metastasis in never smokers with advanced adenocarcinoma of the lung

This study investigated whether epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) increase the development of leptomeningeal metastasis (LM) compared with standard chemotherapy in EGFR mutation-enriched non-small cell lung cancer. The incidence of LM was longitudinally assessed in never smokers with advanced adenocarcinoma of the lung enrolled in a phase III randomized controlled study that compared gefitinib with gemcitabine plus cisplatin (GP) as first-line therapy (The First-SIGNAL study). Among 203 patients who were enrolled at the National Cancer Center Hospital (Goyang, Republic of Korea), LM occurred in 32 (15.8%) with a minimum follow-up time of 55.1months. The 1-, 2-, and 3-year actuarial incidence rates of LM were 5.3, 10.6, and 24.6%, respectively. During first-line treatment, LM occurred in 2 patients (2.0%) treated with gefitinib and in 3 patients (3.2%) treated with GP. There was no difference in the incidence of LM during first-line treatment between the two groups (P=0.934). The incidence of LM was significantly increased during second-line EGFR-TKI treatment compared with first-line EGFR-TKI treatment (P=0.041). During the disease course, the cumulative incidence of LM was not significantly different between the two treatment groups (P=0.514). The median time to LM was 21.4 and 24.0months in the gefitinib and GP groups, respectively (P=0.895). Similar trends were observed in the subset analysis with 23 EGFR-mutant patients. In conclusion, LM predominantly occurred in the late phase of disease in this population. EGFR-TKIs did not affect the incidence or timing of LM development.

Efficacy and tolerability of biweekly gemcitabine plus cisplatin (GEMCIS) or gemcitabine plus paclitaxel (GEMPAC) as neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder.

e15006 Background: Cisplatin, gemcitabine and paclitaxel are active chemotherapeutic agents for invasive urothelial carcinoma of the bladder (UCB). Biweekly administration of gemcitabine in combination with cisplatin (GEMCIS) or paclitaxel (GEMPAC) has been reported to have better tolerability than other schedules. Methods: Between 2009- 2011, we have treated 34 patients (median age 69 years, range 56-85) with muscle invasive UCB using gemcitabine (1500 mg/m2) in combination with cisplatin (50 mg/m2) or paclitaxel (150 mg/m2) given on days 1 and 15, every 4 weeks, for 3 cycles prior to radical cystectomy (RC) with bilateral pelvic lymph node dissection and urinary diversion. Patients deemed unsuitable for GEMCIS due to old age, frailty, multiple comorbidities or poor renal function received GEMPAC (n=9); all others received GEMCIS (n=25). Results: Clinical staging revealed T2, T3 and T4 disease in 20 (58.8 %), 8 (23.5 %) and 6 (17.6 %) patients, respectively. Patients were re-evaluated after 2 cycles with MRI or CT scans, which showed improvement in 21 (61.8 %) patients, no change in 12 (35.3 %) and progression in 1 patient (2.9%). Pathologic examination of the surgical specimens revealed T0, Tis, T2, T3 and T4 disease in 8 (23.5 %), 6 (17.6 %), 10 (29.4 %), 6 (17.6 %) and 4 (11.8 %) patients, respectively. Overall, pathologic downstaging was observed in 41.1% of patients. In the GEMCIS group, 12 patients (48%) had pT0 or pTis; in the GEMPAC group, 2 pts (22.2%) had pT0 disease. The most commonly observed toxicities are tabulated below. Conclusions: Biweekly GEMCIS or GEMPAC regimens were active and exceptionally well tolerated in the neoadjuvant setting in patients with muscle invasive UCB, producing favorable pathologic outcomes in an initial cohort of patients. To our knowledge, these data represent the first report detailing clinical results with these regimens in this setting. [Table: see text]