Gemcitabine Cisplatin Research Articles

Effects of fire needle on quality of life in patients with chemotherapy of non-small cell lung cancer

To observe the effect difference between fire needle combined with chemotherapy and fire needle on quality of life in patients with chemotherapy of non-small cell lung cancer (NSCLC). With randomized controlled method, a total of 60 patients with chemotherapy of NSCLC were divided into an observation group (fire-needle plus chemotherapy group) and a control group (chemotherapy group), 30 cases in each one. The observation group was treated with fire needle at Sihua points which consisted of Geshu (BL 17) and Danshu (BL 19), combined with chemotherapy selected from TP (paclitaxel+cisplatin)/GP (gemcitabine+cisplatin)/DP (docetaxel+cisplatin)/NP (vinorelbine+cisplatin) by the oncologist according to patients' condition. The fire needle was given once a day for 7 days, and chemotherapy was given for 21 days. The control group was treated with chemotherapy alone for 21 days. Before and after treatment, response evaluation criteria in solid tumors (RECIST) was applied for evaluation, and Karnofsky performance status (KPS) and functional assessment of cancer therapy-lung (FACT-L) were applied for evaluation of quality of life in patients with chemotherapy of NSCLC. The effective rate was 20.0% (6/30) and the stability rate was 73.3% (22/30) in the observation group, which were insignificantly higher than 16.7% (5/30) and 63.3% (19/30) in the control group, respectively (both P>0.05). The KPS after treatment was lower than that before treatment in the control group (P<0.05); the KPS after treatment was similar to that before treatment in the observation group (P>0.05); the KPS in the observation group after treatment was higher than that in the control group (P<0.05). The total score and each item score of FACT-L after treatment were higher than those before treatment in the observation group (all P<0.05); the physical score and emotional score of FACT-L after treatment were higher than those before treatment in the control group (both P<0.05); the total score, physical score, functional score and subscale score in the observation group were significantly higher than those in the control group after treatment (all P<0.05), while the social/family score and emotional score in the observation group were insignificantly higher than those in the control group (both P>0.05). The differences of KPS total score before and after treatment in the two groups had moderate positive correlation with differences of FACT-L total score (P<0.01). Fire needle can improve quality of life in patients of NSCLC chemotherapy.

MS 14.03 Estimating Prognosis - How Accurate Can We Be?

MS 14.03 Estimating Prognosis - How Accurate Can We Be?

P-213 - Gemcitabine cisplatin regimen in patients with advanced or metastatic pancreatic cancer (AMPC)

P-213 - Gemcitabine cisplatin regimen in patients with advanced or metastatic pancreatic cancer (AMPC)

IFCT-GFPC-1101 trial: A multicenter phase III assessing a maintenance strategy determined by response to induction chemotherapy compared to continuation maintenance with pemetrexed in patients (pts) with advanced non-squamous (NSQ) NSCLC.

9003 Background: Benefit coming from maintenance treatment appears greater for switch maintenance in pts with disease stabilization (SD) while it might be larger for continuation maintenance in pts with objective response (OR). This study assessed a maintenance strategy conditioned by response to cisplatin-gemcitabine (CG): continuation maintenance with G for pts with OR and switch maintenance with pemetrexed (P) for pts with SD compared with a control arm using P continuation maintenance following cisplatin-pemetrexed (CP) induction regimen. Methods: Eligibility criteria included age 18-70 years, PS of 0-1, untreated stage IV NSQ NSCLC without EGFR mutation or ALK rearrangement, ineligibility to bevacizumab. Pts were randomized 1:1 to receive either experimental CG arm: CG (4 cycles) followed by G maintenance in case of OR followed by second-line P or switch maintenance with P for pts with SD, or standard CP arm: 4 cycles CP induction regimen followed by maintenance P. Overall survival (OS) was the primary endpoint; secondary endpoints included PFS, response rate and safety. Results: Between Jul 2012 and Jun 2016, 932 pts were randomized (CG: 467, CP: 465). Pts characteristics were balanced between the arms. 255 pts (54.6%) in the CG arm received maintenance treatment (G: 142, P: 113) while 274 pts (58.9%) received P maintenance in the CP arm. Median number of maintenance cycles was 5 for G and 4 for P in both arms. The OS adjusted HR was 0.97 (95% CI 0.84, 1.13; p=0.72); median OS: 10.9m CG vs. 10.4m CP. The HR for PFS was 0.96 (95% CI 0.84, 1.10; p=0.56); median PFS: 5.0m CG vs. 4.7m CP. Safety profile was as expected during induction chemotherapy. During maintenance, grade ≥3 hematological AEs occurred in 28% and 31% of pts in CG and CP, respectively, with febrile neutropenia (2.4% vs. 1.1%), anemia (9.4% vs. 11.7%), thrombocytopenia (6.7% vs. 5.8%). No grade ≥3 non-hematological AEs occurred in &gt;5% of pts except for asthenia (3.9% CG vs. 5.1% CP). Conclusions: Adapting maintenance strategy according to response to induction chemotherapy does not improve patient outcome. Clinical trial information: NCT01631136.

Analysis of multidrug resistant transporter expression in tumor blood vessels of urothelial carcinoma during chemotherapy.

e23004 Background: ABCB1, a multidrug transporter, is encoded by multidrug resistance (MDR) 1 gene and plays a major role in drug resistance. Recently, we have reported that not only tumor cells, tumor vascular endothelial cells (TECs) also confer cancer drug resistance. We isolated TECs and found that they have various abnormalities such as aneuploidy or stemness characteristics. TECs showed resistance to Paclitaxel (PTX) with ABCB1 up-regulation. Furthermore, their resistance to PTX was abrogated by ABCB1 inhibition of TECs in vivo. In clinical urology, gemcitabine / cisplatin (GC) is standard 1st line chemotherapy for metastatic urothelial carcinoma (mUC). PTX is often selected in 2nd line chemotherapy for GC resistant cases, however the therapeutic outcomes are limited. We hypothesized that ABCB1 inhibitor/PTX combination would be more effective strategy for mUC, if TEC ABCB1 expression is upregulated. In this study, we investigated ABCB1 expression in tumor blood vessels of UC during 1st line chemotherapy. Methods: Paraffin-embedded samples were corrected from 50 patients who were performed tumor resection before and after 1st line chemotherapy. ABCB1 expressions were analyzed by immunohistochemical staining and the ratio of ABCB1 positive (+) vessels in total vessels were quantified. In vitro assays were performed to address how endothelial cells (ECs) are affected by change of tumor microenvironment during chemotherapy. Results: The ABCB1 (+) vessels were 0.00 – 16.80% (Median 0.00%) and 0.00-58.94% (Median 4.49%), before and after chemotherapy, respectively. In 32 of 50 cases (64%), the ratio of ABCB1 (+) vessels increased after 1st line chemotherapy. Additionally, gemcitabine induced MDR1 mRNA expression in ECs via NF-kB activation. Furthermore, gemcitabine and cisplatin induced IL-8 secretion from tumor cells, and MDR1 mRNA expression level was elevated in ECs. Conclusions: It was suggested that conventional chemotherapy may cause inflammatory change in tumor tissues, which causes in ABC transporter induction in tumor blood vessels. It was suggested that inhibition of ABC transporter in TECs is one of important new strategy to overcome cancer drug resistance.

A phase I study of oral SRA737 (formerly CCT245737) given in combination with gemcitabine plus cisplatin or gemcitabine alone in patients with advanced cancer.

TPS2613 Background: SRA737 is a highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key cell cycle checkpoint and central regulator of the DNA Damage Response (DDR) network. In cancer cells, replication stress induced by genomic alterations in oncogenes (eg, MYC and RAS) combined with loss of function in tumor suppressors (eg, TP53 and ATM) results in persistent DNA damage and genomic instability. Targeted inhibition of components of the DDR network such as Chk1 by SRA737 may be synthetically lethal to cancer cells. Chk1 is also believed to facilitate tumor cell resistance to chemotherapy or radiation-induced DNA damage and the combination of SRA737 with these standards-of-care may provide synergistic antitumor activity. SRA737 is being investigated in two Phase 1 trials in patients with advanced cancer. We now describe the Phase 1 multicenter, dose-escalation study of SRA737 in combination with gemcitabine/cisplatin (GC) or gemcitabine (G) alone (NCT02797977). Methods: Up to 70 patients will receive escalating doses of SRA737+GC in Stage 1 or SRA737+G in Stage 2 until a recommended Phase 2 dose (RP2D) is established, followed by expansion cohorts. Patients will receive a single SRA737 PK run-in dose followed by Gem on D1 and 8, Cis on D1, SRA737 on D2, 3, 9 and 10 of each 21-d cycle or Gem on D1, 8 and 15, SRA737 on D2, 3, 9, 10, 16, 17 of each 28-d cycle. Eligibility criteria include WHO performance status of 0-1 and ≤ 3 prior lines of cytotoxic chemotherapy for metastatic disease. Primary objectives are to assess the safety profile of SRA737 combination therapy and to establish a RP2D. The PK profile and PD biomarkers (eg, phosphorylation of Chk1 at Ser296, Ser345 and γH2AX foci in PBMCs and tumor tissue) will be explored. The study was opened to enrollment in mid-2016. An amendment, which includes the addition of an indication specific expansion cohort of subjects with genetically-defined tumors known to have Chk1-sensitizing aberrations (eg, gene mutations and amplifications/deletions), has been submitted and is pending regulatory review while enrollment continues. At the Annual Meeting, the amended design will be described. Clinical trial information: NCT02797977.

Induction gemcitabine cisplatin followed by chemoradiation in locally advanced nasopharyngeal cancer.

6027 Background: The current standard of treatment in locally advanced nasopharyngeal cancer is concurrent chemoradiation, however recent addition of induction chemotherapy in the already established regimen has presented an attractive alternative approach. We report on survival with induction Gemcitabine and Cisplatin (GC) followed by chemoradiation (CRT) in the treatment of advanced nasopharyngeal carcinoma. Methods: Between 2005 and 2015, 300 patients (M 70%: F 30%) with histologically confirmed nasopharyngeal carcinoma. Histological subtypes WHO I 4% (13) and WHO III 96% (287). AJCC (7th edition) stage was Stage III 28% (85) and Stage IV 72% (215) patients. IC included a 2 drug combination; intravenous gemcitabine 1000 mg/m2 on day 1 and 8 and cisplatin 75 mg/m2 on day 1 only. Radiotherapy was given as a phase treatment to a total dose of 70 Gy in 35 fractions. Concurrent three weekly cisplatin (75 mg/m2) was administered to all patients. Results: Median follow up time was 30 months. The 5-year overall survival (OS), loco regional control (LRC) and relapse free survival (RFS) rates were 70% (95% CI 6.43 – 7.52), 69% (95% CI 6.52 – 7.64) and 52% (95% CI 5.25 – 6.34) respectively. One hundred and seven patients failed treatment; local or loco-regional 39% (42), regional 16% (17) and distant 45% (48). Conclusions: We conclude that induction gemcitabine and cisplatin followed by chemo-radiation is an effective regimen in management of nasopharyngeal carcinoma, meriting further investigation in randomized clinical trials.

Metastatic non-muscle invasive bladder cancer with meningeal carcinomatosis: case report of an unexpected response

BackgroundNon-muscle invasive bladder cancer (NMIBC) is usually treated with local therapy including transurethral resection of the bladder tumor and intravesical therapy depending on the stage of the tumor. NMIBC is a rarely a metastatic diseases with lymph node invasion in less of 10%. In the other hand meningeal carcinomatosis is a rare location for metastases with extremely poor outcomes. We described a case report of a patient presenting a metastatic disease to bones and meninges, several years after the treatment of NMIBC, which had been in complete response (CR) for 4 years after chemotherapy treatment.Case presentationA 63-years old men was treated by TURBT in 2008 for a high grade NMIBC, pT1b. Three years later he presented an acute binocular diplopy with right trochlear nerve paralysis, and labial hypoesthesia. Brain scan and MRI were performed finding a clivus infiltration and a pachymeningitis. A vertebral biopsy was performed finding an invasive carcinoma, CK7+/CK20+, TTF1-, PSA-, Thyroglobulin- and GATA3+. The metastatic event was in relation to the high grade NMIBC treated 3 years previously. Palliative chemotherapy was started with cisplatin gemcitabine. After 6 cycles and to date, 4 years later, the patient is therefore considered in complete response.ConclusionMetastasis in non-muscle invasive urothelial carcinoma is rare. Meningeal carcinomatosis outcome is poor, usually appearing in widely metastatic and progressive cancers but also because most systemic agents fail to pass the blood-brain barrier and penetrate into the cerebrospinal fluid. We described an unexpected response with complete response after chemotherapy for meningeal carcinomatosis of non muscle invasive urothelial carcinoma.

Gemcitabine-cisplatin versus gemcitabine-oxaliplatin doublet chemotherapy in advanced gallbladder cancers: a match pair analysis.

Gemcitabine-cisplatin (GC) and gemcitabine-oxaliplatin (GO) are the most commonly used regimens in advanced gallbladder cancer (GBC). The data of patients with advanced GBC, treated between January 2013 and June 2015 were retrieved. A 1:1 matching without replacement was performed by using nearest neighbor matching method. A total of 326 patients (163 GC and 163 GO), were matched 1:1 by age and gender. The response rates for GC and GO were 31.2% and 36.3% (P = 0.350). The overall median event free survival (EFS) was 4.34 months (95% CI 4.030-4.644 months). The median EFS was 4.67 months (95% CI 4.060-5.271 months) in GC cohort and 3.88 months (95% CI 3.369-4.385 months) in GO cohort (P = 0.023). The overall median OS was 8.016 months (95% CI 7.361-8.672 months). The median OS was 8.02 months (95% CI 7.257-8.776 months) in GC cohort and 7.79 months (95% CI 6.690-8.88 months) in GO cohort (P = 0.455). The incidence of Grade 2/3 peripheral neuropathy (9.2% vs. 3.1%; P = 0.445) and Grade 3/4 transamintis (14.7% vs. 6.1%) was higher with GO while the incidence of anemia (22.1% vs. 6.7%; P < 0.001), neutropenia (7.3% vs. 2.4%; P = 0.49) and thrombocytopenia (9.8% vs. 3.7%; P = 0.033) was higher with GC. Gemcitabine-cisplatin or gemcitabine-oxaliplatin can be used as an initial regimen in advanced GBC. Higher EFS, potentially lower costs, lower incidence of peripheral neuropathy and hepatotoxicity favor the use of GC, whereas a lower incidence of hematological toxicities, and potential ease of administration in patients with borderline renal and cardiac functions favor GO.

Treatment of advanced Gall bladder cancer in the real world-can continuation chemotherapy improve outcomes?

Gemcitabine-Platinum doublet chemotherapy is the standard of care in patients with locally advanced inoperable and metastatic (LA/M) Gall bladder cancers (GBC). Consecutive patients with LA/M GBC treated with Gemcitabine-Cisplatin (GC) or Gemcitabine-Oxaliplatin (GO) as first line palliative chemotherapy from January 2013 to June 2015 were retrospectively analysed. Patients who were able to continue chemotherapy beyond 6-8 cycles were separately compared to those who were potential candidates for this approach, but chose not to continue chemotherapy. A total of 396 patients received first line palliative chemotherapy during the period of analysis, 276 patients (69.6%) were unable to complete 6-8 cycles of chemotherapy, while 120 patients (30.4%) were potential candidates for continuing chemotherapy. Seventy patients (n=120; 58.3%) received a median of 4 cycles of continuation chemotherapy. Median overall survival (OS) for the entire cohort was 7.65 months [95% confidence interval (CI), -7.14 to 8.16], while median event free survival (EFS) was 4.53 months (95% CI, -4.23 to 4.83). Patients receiving continuation chemotherapy had a statistically improved median OS compared to all other patient cohorts, 14.88 months (95% CI, -12.48 to 17.27; P=0.005 on multivariate analysis). Burden/number of sites of metastases, receiving of continuation chemotherapy, fit and able to receive second line chemotherapy (CT2) were identified on multivariate analysis as prognostic factors for OS. OS in our study appeared lower than published literature, but a group of patients were identified whose survival could be prolonged by continuing chemotherapy. Easily available factors can predict prognosis of GBC undergoing first line palliative chemotherapy.

Association of chemotherapy regimen with venous thromboembolic risk in patients with urothelial tract cancer.

314 Background: Cisplatin chemotherapy (CTX) is associated with increased risk of venous thromboembolism (VTE); however, other agents have also been hypothesized to increase risk. We assessed the association of VTE with different CTX regimens in urothelial tract cancer patients. Methods: We identified &gt; 66 year-old patients diagnosed with urothelial tract cancers (excluding renal pelvis) from the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database from 1998 to 2011. CTX regimens included gemcitabine/cisplatin (GC), methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), or gemcitabine/carboplatin (GCarbo). We calculated VTE rates within 120 days of CTX initiation and compared VTE by CTX regimen with multivariable logistic regression models adjusted for patient and cancer characteristics. Results: Of 5050 identified patients, VTE occurred in 13.1% (660/5050). VTE rates were 15.3% (265/1737) and highest for GC; 8.8% (23/262) and 12.2% (372/3051) of MVAC and GCarbo patients experienced VTE, respectively. Adjusted for patient demographic and cancer-specific variables, MVAC and GCarbo were associated with lower odds of VTE compared with GC (see Table). Conclusions: Compared with GC, MVAC and GCarbo are associated with a decreased rate of VTE. This finding suggests that gemcitabine may add to the increased thrombosis risk from cisplatin. Patients treated with GC should be counseled about this association. Sensitivity analyses to assess VTE risk of different CTX regimens in the perioperative setting will be presented. [Table: see text]

Outcomes of second line treatment in patients with advanced and metastatic biliary cancers.

420 Background: Advanced biliary cancers respond poorly to chemotherapy and have a dismal survival. Currently gemcitabine-cisplatin (GC) is the standard of care for patients with advanced disease. The efficacy of second line treatment options is not well-defined. We retrospectively evaluated outcomes of patients undergoing second line treatment for advanced biliary cancers at Mayo Clinic. Methods: After obtaining approval from the institutional board review (IRB), we identified 42 patients with advanced and metastatic biliary cancers that progressed after first line (GC) and received second line treatment from 2007-2014. All patients had adequate follow up data. JMP software was used for statistical analysis. Kaplan-Meier method and log-rank tests were used for survival analysis, and multivariate cox proportional hazards model was used to evaluate the prognostic effect of pertinent clinical variables. All tests were two sided and a P value of &lt; 0.05 was considered significant. Results: The median age at diagnosis was 61.5 (range 26-87). The most common regimens used for second line settings were 5-FU-based (69%) followed by gemcitabine-based regimens (19%). The overall response rate (ORR) was 9.1%, while the disease control rate (DCR; stable disease and partial response) was 33%. The median overall survival (mOS) for the entire cohort from first line was 16.8 months (95% CI 12.7-21.7) and the progression-free survival (PFS) was 9.16 months (95% CI 7.3-14.7). From second line start the mOS was 10.4 months (95%; CI 7.3-23.7), and PFS was 2.8 months (95% CI 2.3-4.0). 73% of patients who received second line therapy were alive at 6 months and 50% at 12 months. 25 patients received third line treatment after progression. An univariate and multivariate analysis were performed including age, sex, stage at diagnosis, regimen used, CA19-9 and total body weight loss &gt; 5%, but no significant prognostic factors were identified. Conclusions: Patients with biliary cancers who progress after first line treatment have poor prognosis, but may benefit from second line regimens. 5-FU based regimens were the most commonly used in the second line setting, and 73% of patients who received second line therapy were alive at 6 months.

OA23.02 Efficacy and Safety of Necitumumab Continuation Monotherapy in Patients with EGFR-Expressing Tumors in SQUIRE, a Phase 3 Study

SQUIRE (NCT00981058) demonstrated adding necitumumab (N) to gemcitabine/cisplatin (GC) improved survival in patients with Stage IV squamous NSCLC (SQ-NSCLC). Retrospective analysis revealed consistent treatment effect in favor of patients receiving N monotherapy as continuation after chemotherapy (CT) (GC+N continuation patients) versus continuation therapy-eligible GC arm patients (GC non-progressors). In the EU, N is approved for patients with EGFR-expressing tumors. We repeated the analysis in this patient population. Patients with Stage IV SQ-NSCLC were randomized 1:1 for ≤6 cycles of G (1250 mg/m2 iv, Days [d] 1,8) and C (75 mg/m2 iv, d1) either with or without N (800 mg iv, d1,8). Patients in GC+N without progression continued N until progressive disease (PD). SQUIRE included mandatory tissue collection. EGFR protein expression was assessed by IHC in a central lab (Dako EGFR PharmDx kit). Analyses were done in EGFR-expressing patients (EGFR >0). Patients who received ≥4 cycles of CT without PD were included. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier method. 95% CIs and hazard ratios estimated using stratified Cox proportional hazards model. Of 1093 patients (ITT population), 982 patients (89.8%) had evaluable IHC assay results; 935/982 (95.2%) had EGFR>0. GC+N arm continuation therapy patients included 228 patients with EGFR>0 and 194 patients (EGFR>0) were GC arm non-progressors. Baseline characteristics were similar except gender (Males: 81% in GC+N vs 91% in GC arm). CT exposure was balanced. Median OS from randomization in GC+N vs GC was 16.1 vs 14.9 months; HR 0.76 (95% CI, 0.61, 0.95). Median PFS in GC+N vs GC was 7.4 vs 6.9 months; HR 0.81 (95% CI, 0.66, 1.00). In patients with EGFR-expressing tumors, a consistent treatment effect in favor of GC+N continuation maintenance compared to GC non-progressors was observed, similar to ITT population with no unexpected increases in AEs.

MTE17.02 Maintenance Therapy versus Early Second-Line Therapy in Advanced NSCLC

MTE17.02 Maintenance Therapy versus Early Second-Line Therapy in Advanced NSCLC

Neoadjuvant chemotherapy with methotrexate/vinblastine/doxorubicin/cisplatin vs. gemcitabine/cisplatin for muscle-invasive bladder cancer: a review and meta-analysis

Objective To systematically assess the efficacy of neoadjuvant chemotherapy (NAC) with methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) vs. gemcitabine/cisplatin (GC) for muscle-invasive bladder cancer (MIBC). Methods Randomized controlled trials (RCTs) or non-RCTs regrading the efficacy of NAC with MVAC vs. GC for MIBC were retrieved in Pubmed, Cochrane library, Sciverse, CNKI, VIP and Wanfang database from databases establishment to May 2016. According to the including and exclusion criterion, two reviewers independently reviewed the trials, conducted the Meta-analysis with RevMan 5.3 soft ware. Results A total of 13 non-randomized clinical controlled trials were eligible for the study including 1690 cases. The pooled results showed that MVAC group had a lower down staging rate (RR=0.77, 95%CI 0.61-0.97, P=0.03) and complete response rate (RR=0.70, 95%CI 0.53-0.93, P=0.01). Statistically significant were observed. However, there was no significant difference in disease free survival (RR=0.88, 95%CI 0.60-1.29, P=0.53). Conclusion Compared with MVAC, NAC with GC had higher down staging rate and complete response rate. Therefore, NAC with GC should be considered as a preferable option for MIBC. Key words: Muscle invasive bladder cancer; Methotrexate/vinblastine/doxorubicin/cisplatin (MVAC); Gemcitabine/cisplatin (GC); Neoadjuvant chemotherapy; Meta analysis

Impact of anticancer drugs price cut on physician's prescription choices on first-line chemotherapy regimens and health expenditure for advanced non-small cell lung cancer in China.

Increases in insurance coverage and price cut of drugs are two important measures to make health care more accessible and affordable. As far as we know, this was the first study to explore the impact of anticancer drug price cut on health expenses and oncologist's prescription decisions in China. The 511 non-small cell lung cancer (NSCLC) patients were recruited from Qilu Affiliated Hospital of Shandong University from January 1, 2003 to December 31, 2010. We categorized the patients into five groups based on China's fifth population census in 2000, including administrative group, workers and services group, peasants group, professionals group and others group. All statistical analyses were performed using SPSS (version 16.0), all statistic tests were two-tailed and P value ≤0.05 was considered significant. As for the first-line chemotherapy regimens prescribed during the study, 27.6% patients received vinorelbine + cisplatin (NP), 31.5% and 30.9% patients had gemcitabine + cisplatin (GC) and docetaxel + cisplatin (DC), respectively, while only 4.3% patients received paclitaxel + cisplatin or carboplatin (TP). Before price policy implementation, NP was the most popularly used regimen (44.6%). By contrast, doctors' prescription choices changed significantly after drug price cut, GC took first place (42.0%). GC became the most expensive regimen (4,431.40 RMB per cycle, about 665.15 dollars per cycle), while NP cost the least (1,974.48 RMB per cycle, about 296.37 dollars per cycle) after price cut. No significant reduction could be seen for both the pharmaceutical spending and total expense per inpatient episode after drug price adjustment. One interesting phenomena was that doctors relied less on patient's sex, age, histology to make their decisions, by contrast, more on patient's occupation and health insurance type. And, the total drug cost was closely related to patient occupation and health insurance type. The introduction of anticancer drug price control policy was found to be ineffective on the containment of hospital drug expenditures in one cancer center in China.

A05 - SQUIRE: a randomised, multicentre, open-label, phase III study of gemcitabine-cisplatin (GC) plus necitumumab (N) versus GC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC); Subgroup efficacy and safety data for pts with epidermal growth factor receptor (EGFR)-expressing tumours

A05 - SQUIRE: a randomised, multicentre, open-label, phase III study of gemcitabine-cisplatin (GC) plus necitumumab (N) versus GC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC); Subgroup efficacy and safety data for pts with epidermal growth factor receptor (EGFR)-expressing tumours

Correlation of EGFR-expression with safety and efficacy outcomes in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine–cisplatin plus necitumumab versus gemcitabine–cisplatin alone in the first-line treatment of patients with stage IV squamous non-small-cell lung cancer

SQUIRE demonstrated addition of necitumumab to gemcitabine and cisplatin significantly improved survival in patients with stage IV sq-NSCLC. Here, we report additional outcomes for the subpopulation of patients with tumor epidermal growth factor receptor (EGFR) protein expression. Patients with pathologically confirmed stage IV sq-NSCLC were randomized 1:1 to receive a maximum of six 3-week cycles of gemcitabine (1250 mg/m(2) i.v., days 1 and 8) and cisplatin (75 mg/m(2) i.v., day 1) chemotherapy with or without necitumumab (800 mg i.v., days 1 and 8). Patients in the chemotherapy plus necitumumab group with no progression continued on necitumumab alone until disease progression or intolerable toxicity. SQUIRE included mandatory tissue collection. EGFR protein expression was detected by immunohistochemistry (IHC) in a central laboratory. Exploratory analyses were pre-specified for patients with EGFR protein expressing (EGFR > 0) and non-expressing (EGFR = 0) tumors. A total of 982 patients [90% of intention-to-treat (ITT)] had evaluable IHC results. The large majority of these patients (95%) had tumor samples expressing EGFR protein; only 5% had tumors without detectable EGFR protein. Overall survival (OS) for EGFR > 0 patients was significantly longer in the necitumumab plus gemcitabine-cisplatin group than in the gemcitabine-cisplatin group {stratified hazard ratio (HR) 0.79 [95% confidence interval (CI) 0.69, 0.92; P = 0.002]; median 11.7 months (95% CI 10.7, 12.9) versus 10.0 months (8.9, 11.4)}. Additionally, an OS benefit was seen in all pre-specified subgroups in EGFR > 0 patients. However, OS HR for EGFR = 0 was 1.52. Adverse events of interest with the largest difference between treatment groups in EGFR > 0 patients (Grade ≥3) were hypomagnesemia (10% versus <1%) and skin rash (6% versus <1%). In line with SQUIRE ITT, addition of necitumumab to gemcitabine-cisplatin significantly prolonged OS and was generally well tolerated in the subpopulation of patients with EGFR-expressing advanced sq-NSCLC. The benefit from addition of necitumumab to chemotherapy was not apparent in this analysis for the small subgroup of patients with non-EGFR-expressing tumors. NCT00981058.

Abstract 449: Targeted proteomic analysis for personalized treatment of muscle invasive bladder cancer

Abstract Background: Standard treatment for muscle-invasive bladder cancer (MIBC) includes chemotherapy with either gemcitabine-cisplatin (GC) or methotrexate, vinblastine, adriamycin and cisplatin (MVAC). These regimens have similar clinical complete response rates of approximately 30%. While no targeted treatment has been approved for bladder cancer, clinical trials have identified biochemical markers that predict the chemoresponsiveness of MIBC tumors to specific chemotherapeutic agents. For example, patients with high hENT1 and low RRM1 expression responded better to GC-based chemotherapy than their counterparts, and HER2 overexpression predicted resistance to cisplatin-based therapy. To quantify targets that are known indicators of tumor behavior, we used targeted proteomic analysis to assess 30 different protein biomarkers in formalin-fixed paraffin-embedded (FFPE) MIBC tumor tissue. Methods: Twelve FFPE MIBC tissue blocks were obtained and a pathologist marked a minimum 8mm2 of tumor area from 1 or 2 slides. Following laser microdissection of the marked areas, proteins were extracted using the Liquid-Tissue® process and subjected to selected reaction monitoring mass spectrometry to quantify the amounts of 30 different targeted proteins in each patient sample. Results: Of the 12 patient samples, 7 (58%) expressed high levels of hENT1 and 11 (92%) expressed low levels of RRM1, indicating that gemcitabine-based therapy would be an appropriate choice. A single patient expressed high levels of RRM1, an indication for non-gemcitabine based therapy. All 12 patients expressed TUBB3, a marker of resistance to taxane (vinblastine) and 10 patients (83%) lacked expression of FR-alpha, a marker of sensitivity to methotrexate. The majority of patients expressed a marker of sensitivity to anthracycline (TOPO2A) and did not express a resistance biomarker for platinum therapy (ERCC1). Of 3 patients whose tumors expressed HER2, 2 had overexpression (&amp;gt;750 amol/ug) and would thus be eligible for HER2 basket trials. Further, multiplex-targeted proteomics discovered patients expressing FGFR1 (17%), cMET (33%), Axl (17%) and IDO1 (25%), which would make them eligible for clinical trials of targeted or immunotherapies. Conclusion: MIBC is heterogeneous and expresses a wide range of proteins. Yet, it continues to be treated with only 2 chemotherapeutic regimens. Multiplexed proteomics is currently being used in clinical practice to inform personalized patient care decisions with identification and the relative quantities of actionable proteins known to predict tumor behavior. Citation Format: Fabiola Cecchi, Sheeno Thyparambil, Adele Blackler, Todd Hembrough, Shahrooz Rabizadeh, Patrick Soon-Shiong, Henry Frierson, Daniel Theodorescu. Targeted proteomic analysis for personalized treatment of muscle invasive bladder cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 449.

化疗对非小细胞肺癌患者外周血中CD8+CD28-T细胞表达的影响

Objective To observe the expression of CD8+ CD28-T cells in the peripheral blood of non-small-cell lung cancer (NSCLC) patients, and to investigate the effect of chemotherapy on CD8+ CD28-T cells expression and its clinical significance. Methods Flow cytometry was used to evaluate the level of CD8+ CD28-T cells in peripheral blood of 70 untreated NSCLC patients and 60 healthy controls. The association between CD8+ CD28-T cells and the clinical features was analyzed. We also investigated the changes of CD8+ CD28-T cells in 30 NSCLC patients who received chemotherapy by GP (gemcitabine, cisplatin) and NP (navelbine, cisplatin). Results The proportion of CD8+ CD28-T cells in lung cancer group was significantly higher than that in healthy group (59.003%±15.329% vs. 41.036%±15.435%, t=35.904, P=0.001). No correlation was found between CD8+ CD28-T cells expression and the gender (F=1.374, P=0.697), pathological pattern (F=0.779, P=0.509) and clinical stage (F=0.070, P=0.933). But CD8+ CD28-T cells expression was correlated with the age (F=15.038, P=0.001). The level of CD8+ CD28-T cells after NP chemotherapy was lower than that before chemotherapy (55.293%±14.637% vs. 58.793%±12.510%, t=2.017, P=0.044). And the level of CD8+ CD28-T cells after GP chemotherapy was lower than that before chemotherapy (54.127%±13.924% vs. 60.700%±16.401%, t=3.007, P=0.009). Conclusion CD8+ CD28-T cells express highly in NSCLC patients peripheral blood. Chemotherapy down-re-gulates CD8+ CD28-T cells expression, which provides a new reference for combination with chemotherapy and immunotherapy in NSCLC patients. Key words: Carcinoma, non-small-cell lung; Drug therapy; CD8-positive T-lymphocytes