Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15111-15111 ◽  
Author(s):  
Y. Park ◽  
S. Yi ◽  
H. Kim ◽  
S. Lee ◽  
I. Hwang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stable Disease ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Median Number ◽  
Line Treatment ◽  
Second Line ◽  
Best Response ◽  
Grade 3 ◽  
Number Of Cycles

15111 Background: The aim of this phase II study was to determine whether second line therapy with single agent irinotecan could provide any clinical benefit in patients with gemcitabine- pretreated advanced pancreatic cancer. Methods: From January 2004 to October 2006, patients with advanced pancreatic cancer previously treated with gemcitabine alone or combination were treated with single agent irinotecan(150 mg/m2, biweekly), until unacceptable toxicity or disease progression. Primary endpoint was response rate with single stage design. Results: Twenty-eight patients were enrolled(22 male, 6 female, median age : 54.5 years (39–76)). Nine patients are still alive and 3 remain on therapy with stable disease. The median number of cycles was 3.5(1–12). Twenty-four patients were assessable for toxicity and 21 for response. The most common toxicities was diarrhea (grade 3, 12.5%). Grade 3 neutropenia in 1 patient was observed. Other hematological and non-hematological toxicities were mild and manageable. Partial responses were observed in 3 patients (3/21, 14%). An additional 9 patients (9/21, 43%) had stable disease as their best response. 12 patients have progressed with a median time-to-progression of 4.0 months. Conclusions: Single-agent irinotecan was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced pancreatic cancer, refractory to gemcitabine. No significant financial relationships to disclose.

Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Kotone Hayuka ◽  
Hiroyuki Okuyama ◽  
Akitsu Murakami ◽  
Yoshihiro Okita ◽  
Takamasa Nishiuchi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Unresectable Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Common Grade ◽  
Grade 3

<b><i>Introduction:</i></b> Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. <b><i>Methods:</i></b> Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. <b><i>Results:</i></b> The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). <b><i>Conclusions:</i></b> GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.

Oral capecitabine in gemcitabine-pretreated patients with advanced pancreatic cancer: A single-center study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15085-15085 ◽  
Author(s):  
S. H. Boeck ◽  
R. Wilkowski ◽  
C. J. Bruns ◽  
R. D. Issels ◽  
C. Schulz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Treatment Regimen ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Previous Treatment ◽  
Median Number ◽  
Salvage Chemotherapy ◽  
Standard Regimen ◽  
Hand Foot Syndrome ◽  
Grade 3

15085 Background: To date, no standard regimen for salvage chemotherapy after gemcitabine (Gem)-failure is defined in patients with advanced pancreatic cancer (PC). Methods: Within this study we prospectively collected clinical data of 37 patients (pts) with advanced PC who were treated with capecitabine (Cape) at our center. Cape was offered to patients who already had received at least one previous treatment regimen containing full-dose Gem (either as single- or combination chemotherapy or sequentially within a radio- chemotherapy (RCT) protocol), who presented with a KPS = 70% and had adequate organ function. Cape was administrated orally at a daily dose of 2 x 1250 mg/m2 for 14 consecutive days followed by 7 days of rest (in pts > 65 years: 2 x 1000 mg/m2/d). Treatment cycles were repeated every 3 weeks and continued until disease progression or unacceptable toxicity. Results: A median number of 3 treatment cycles (range 1–36) was given to 37 pts (54% male, median age 63 yrs, 97% with metastatic disease); 15 pts previously underwent RCT, 20 pts had received one previous treatment regimen and 17 pts 2 or more previous regimens. After a median follow- up of 6.1 months, 10 pts are still alive including 4 pts still on Cape. Currently, 35 pts are evaluable for response: no complete or partial response was observed, but 13 pts (37%) had stable disease (SD). A CA19–9 reduction > 20% after 8 weeks of Cape was determined in 6 pts (16%), all of them had SD. Median TTP was 2.2 months, median overall survival (since start of Cape treatment) was 7.5 months. Predominant grade 2 and 3 toxicities (per patient analysis) were: hand-foot-syndrome 30%, anemia 24%, diarrhea 14%, nausea/vomiting and leukopenia 11% each. One pt had a grade 3 infection, 1 pt experienced grade 4 cerebral ischemia during treatment with Cape. Conclusion: Single-agent Cape is a safe treatment option for Gem-pretreated pts with advanced PC. The disease control rate of 37% and a median TTP of 2.2 months appear interesting in this patient population. Further evaluation of Cape in controlled clinical trails is recommended in Gem-refractory pts with advanced PC. No significant financial relationships to disclose.

Survival benefit of second-line chemotherapy in advanced pancreatic adenocarcinoma: A systematic review of the literature.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 296-296 ◽  
Author(s):  
Adnan Nagrial ◽  
Venessa T. Chin ◽  
Katrin Sjoquist ◽  
Lorraine A. Chantrill ◽  
Desmond Yip
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Response Rates ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

296 Background: There is currently no standard of care for the second-line treatment of advanced pancreatic cancer. Very few randomised studies have been performed in this setting. The aim of this analysis was to compare the different therapeutic approaches in this setting, and the rate of second line treatment delivery and its influence on reported overall survival. Methods: We carried out a systematic analysis of studies in advanced pancreatic cancer. 1st and 2nd line chemotherapy trials were identified from MEDLINE, EMBASE & CENTRAL using the COCHRANE sensitive search strategy. Objective response rates (ORR) and survival (PFS & OS) were extracted and compared amongst groups using the Mann-Whitney U test. For 1st line studies, the percentage of patients who received 2nd line chemotherapy was also extracted and plotted against reported median overall survival (OS) and post-progression survival (PPS), defined as arithmetic difference between median OS and progression-free survival. Linear regression was used to explore the relationship between overall survival and second-line chemotherapy. Results: 20 first line clinical trials with 42 treatment arms met the inclusion criteria treating an aggregate total of 5,768 patients. Overall survival was positively correlated with use of second-line chemotherapy (r=0.65; p=0.012). 61 second-line studies were identified treating an aggregate total of 2,562 patients in 66 treatment arms. Combination treatment was associated with an improved response rate (p=0.045) and PFS (p=0.024) when compared to single agent therapy. Conclusions: In this exploratory analysis, these data suggest that there is a small benefit of second-line chemotherapy in pancreatic cancer. In first-line chemotherapy studies, the use of subsequent treatment correlates with improved overall survival. In second line studies, combination chemotherapy is associated with higher response rates and survival.

scholarly journals Second-Line Gemcitabine Plus Nab-Paclitaxel for Patients with Unresectable Advanced Pancreatic Cancer after First-Line FOLFIRINOX Failure

2019 ◽  
Vol 8 (6) ◽  
pp. 761 ◽  
Author(s):  
Naoki Mita ◽  
Takuji Iwashita ◽  
Shinya Uemura ◽  
Kensaku Yoshida ◽  
Yuhei Iwasa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
First Line Treatment

FOLFIRINOX (FX) and gemcitabine (GEM) plus nab-paclitaxel (GnP) have been reported as effective regimens for unresectable advanced pancreatic cancer (APC). FX may be more effective but is also associated with more adverse events (AEs). Therefore, first-line treatment with FX followed by second-line GnP may be appropriate. Aims: To assess the safety and efficacy of second-line GnP for patients with APC after first-line FX failure. Methods: This study was a multicenter prospective phase II study evaluating second-line GnP in patients with APC after failed first-line FX. The primary endpoint was response rate (RR), and the secondary endpoints were overall survival (OS), progression free survival (PFS), and the frequency and degree of adverse events (AEs). Results: Thirty patients (14 male; median age, 64 years) were enrolled. The RR was 13.3%, with a median follow-up time of 9.3 months. The median OS and PFS were 7.6 and 3.8 months, respectively. From the beginning of first-line treatment, the median OS and PFS were 14.2 and 9.3 months, respectively. Grade 3 or 4 AEs were seen in 70% of patients. Conclusion: Second-line GnP after FX failure for patients with APC could be more effective than GEM alone. Further comparison studies are warranted.

scholarly journals Oxaliplatin and Bolus-Modulated 5-Fluorouracil as a Second-Line Treatment for Advanced Pancreatic Cancer: Can Bolus Regimens Replace FOLFOX When Considered for Second Line?

ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
A. Azmy ◽  
S. Abdelwahab ◽  
M. Yassen
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Clinical Benefit ◽  
Advanced Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Treatment Groups ◽  
Grade 3 ◽  
To Receive ◽  
Advanced Pancreatic Adenocarcinoma

Objective. Comparing activity of 2 regimens combining oxaliplatin to bolus modulated fluorouracil as second line treatment in advanced pancreatic adenocarcinoma pretreated with gemcitabine-containing schedule. Methods. Forty eight patients with advanced pancreatic adenocarcinoma were randomly assigned to receive either FU 500 mg/m2 IV bolus weekly ×6 weeks plus leucovorin 500 mg/m2 IV weekly for 6 weeks during each 8-week cycle plus oxaliplatin 85 mg/m2 IV on weeks 1, 3, and 5 of each 8-week (FLOX) OR receive weekly intravenous infusions of oxaliplatin 40 mg/m2, 5-FU 500 mg/m2, and leucovorin 250 mg/m2 (3 weeks on, 1 week off). Results. Non progression(PR+SD) was found in 33.5% for first regimen and 29% for second regimen, and 37.5% had clinical benefit (FLOX regimen) compared to 50% in 3-weeks regimen. The median TTP was 3.9,4 months respectively. Median OS was 8, 9 months for both regimens. Only one case in 3-weeks arm suffered from grade IV diarrhea. Two cases > grade 2 neutropenia were observed; one in each treatment groups. Grade 3 anemia was recorded in 3 patients (2 in FLOX arm, one in 3-weeks arm). Conclusions. Both regimens showed encouraging efficacy, acceptable toxicity, and clinical benefit.

Second-line chemotherapy in advanced pancreatic cancer: A retrospective, single-center analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15187-15187 ◽  
Author(s):  
T. Herrmann ◽  
D. Jaeger ◽  
W. Stremmel ◽  
C. Herrmann
Keyword(s):  
Pancreatic Cancer ◽  
Disease Progression ◽  
Stable Disease ◽  
Partial Remission ◽  
Advanced Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

15187 Background: Patients with advanced pancreatic cancer profit from palliative chemotherapy. The role of second-line chemotherapy is not yet established. Methods: We performed a retrospective analysis in 98 patients who were treated at our department from 1/2004–6/2006 due to locally advanced or metastatic adenocarcinoma of the pancreas. Results: At the time of analysis 67 patients had died (median overall survival 9 months), 31 patients are still alive (median follow up 9 months). 12 patients were initially treated with radiochemotherapy. 86 patients received systemic chemotherapy; 43 of these patients were treated with second-line chemotherapy after disease progression. OS was significantly longer in patients who received second-line chemotherapy (10 months versus 5.0 months, p=0.023). Response to second-line chemotherapy was partial remission in 2 patients (4.6 %), stable disease in 18 patients (44.8 %), and progressive disease in 19 patients (44.2 %), in 3 patients the treatment was stopped due to toxicity (6.9 %). 12 patients received second-line treatment after early disease progression under first-line chemotherapy. 9 of these patients did not respond to second-line treatment, 2 achieved stable disease and 1 patient had partial remission. Elevated LDH and CA19.9 serum levels at the time of diagnosis were identified as negative prognostic factors. Conclusions: Prognosis of patients with advanced pancreatic cancer is still poor. Selected patients may benefit from salvage chemotherapy after failure of first-line chemotherapy. No significant financial relationships to disclose.

Sindilimab combined with nab-paclitaxel plus gemcitabine as first-line treatment for patients with advanced pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16257-e16257
Author(s):  
Huayun Zhu ◽  
Xiaofeng Sun ◽  
Xuan Pan ◽  
Pingping Wu ◽  
Jia Chen
Keyword(s):  
Pancreatic Cancer ◽  
Primary Endpoint ◽  
Stable Disease ◽  
Single Agent ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Combined Chemotherapy ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

e16257 Background: This study aimed to evaluate the efficacy and safety of Sindilimab combined with nab-paclitaxel plus gemcitabine as first-line treatment for advanced pancreatic cancer. Methods: This was a single-arm, simple-center, exploratory trial, which included advanced pancreatic cancer pts. Patients received Sindilimab combined with nab-paclitaxel plus gemcitabine. Combined chemotherapy lasted for no more than 12 cycles. Once chemotherapy intolerance occurred or at end of 12-cycle combined chemotherapy, pts with stable disease or objective response would continue to take Sindilimab as single agent until disease progression or intolerable toxicity. Response was assessed every 8 weeks. Results: 16 eligible patients were enrolled and 14 pts were evaluable for efficacy analysis. Baseline characteristics are shown in Table 2. Conclusions: This study has showed high anti-tumor efficacy and tolerant toxicity in first-line regimen for advanced pancreatic cancer. Furthermore, it is needed to be proved in update results and large scale studies. Efficacy As shown in Table 3, among 14 evaluable pts, unconfirmed ORR was 57.1% and DCR was 92.8%. 8 pts got partial response (PR), 5 pts stable disease (SD) and 1 pts progressive disease(PD) at best. PFS: The primary endpoint 6-month PFS rate was 2%(95% CI 50.4%-72.4%). Which indicated that the primary endpoint of the study was reached. And mPFS was 7.3 months(95% CI 5.9-8.1). OS: Median OS was not reached and 6m-OS rate was 85.7% (95%CI 5%-91.3%). Safety. All 16 pts were included in the safety analysis (Table 4). The overall AE incidence rate was 93.75% .≥Grade 3 irAE included GGT increased (37.5%) and peripheral neuropathy (6.25%). No TRAE led to death.[Table: see text][Table: see text][Table: see text][Table: see text]

Oxaliplatin Plus Irinotecan Compared With Irinotecan Alone as Second-Line Treatment After Single-Agent Fluoropyrimidine Therapy for Metastatic Colorectal Carcinoma

2008 ◽  
Vol 26 (28) ◽  
pp. 4544-4550 ◽  
Author(s):  
Daniel G. Haller ◽  
Mace L. Rothenberg ◽  
Alfred O. Wong ◽  
Piotr M. Koralewski ◽  
Wilson H. Miller ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Single Agent ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Sensory Disturbances ◽  
Previously Treated ◽  
Grade 3

Purpose To determine whether irinotecan plus oxaliplatin (IROX) is superior to irinotecan alone in patients with metastatic colorectal cancer (CRC) previously treated with single-agent fluoropyrimidines. Patients and Methods A phase III, randomized, open-label, multicenter study of patients with metastatic or recurrent CRC that had progressed or recurred during or after adjuvant or first-line fluoropyrimidines (fluorouracil/leucovorin or capecitabine, the latter only for metastatic CRC). Patients received IROX (irinotecan 200 mg/m2 plus oxaliplatin 85 mg/m2) or irinotecan alone (350 mg/m2) every 3 weeks. Results At the data cutoff (when 447 of 628 randomly assigned patients had died), median overall survival was 13.4 months (95% CI, 12.4 to 14.7 months) and 11.1 month (95% CI, 10.0 to 12.7 months) in the IROX and irinotecan groups, respectively (hazard ratio = 0.78; 95% CI, 0.65 to 0.94; P = .0072). Overall response rate (22% v 7%, respectively; P < .0001), median time to progression (5.3 v 2.8 months, respectively; P < .0001), and improvement in tumor-related symptoms (32% v 19%, respectively; P = .0072) were also improved with IROX as compared with irinotecan. With the exception of granulocytopenia (25% v 13%), diarrhea (28% v 23%), and sensory disturbances (5% v 0%), grade 3 to 4 toxicities were comparable between the IROX and irinotecan groups, respectively. Conclusion IROX is an effective treatment for metastatic CRC that has progressed after first-line fluoropyrimidine therapy. IROX improves efficacy compared with irinotecan alone, providing an additional option in the postadjuvant or second-line treatment setting for patients who experience treatment failure with single-agent fluoropyrimidine therapy.

Gemcitabine Plus Capecitabine Compared With Gemcitabine Alone in Advanced Pancreatic Cancer: A Randomized, Multicenter, Phase III Trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group

2007 ◽  
Vol 25 (16) ◽  
pp. 2212-2217 ◽  
Author(s):  
Richard Herrmann ◽  
György Bodoky ◽  
Thomas Ruhstaller ◽  
Bengt Glimelius ◽  
Emilio Bajetta ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Metastatic Pancreatic Cancer ◽  
Karnofsky Performance Score ◽  
Phase Iii Trial ◽  
Good Performance Status ◽  
Grade 3

PurposeThis phase III trial compared the efficacy and safety of gemcitabine (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic pancreatic cancer.Patients and MethodsPatients were randomly assigned to receive GemCap (oral capecitabine 650 mg/m2twice daily on days 1 to 14 plus Gem 1,000 mg/m2by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m2by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks). Patients were stratified according to center, Karnofsky performance score (KPS), presence of pain, and disease extent.ResultsA total of 319 patients were enrolled between June 2001 and June 2004. Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in patients with good KPS (score of 90 to 100) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months, respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event in both arms.ConclusionGemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.

scholarly journals Phase I clinical trial of the combination of eribulin and everolimus in patients with metastatic triple-negative breast cancer

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Jin Sun Lee ◽  
Susan E. Yost ◽  
Suzette Blanchard ◽  
Daniel Schmolze ◽  
Hongwei Holly Yin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Dose Level ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Median Number ◽  
Primary Objective ◽  
Best Response ◽  
Grade 3 ◽  
Number Of Cycles

Abstract Background Alteration of the PI3K/AKT/mTOR pathway is a common genomic abnormality detected in triple-negative breast cancer (TNBC). Everolimus acts synergistically with eribulin in TNBC cell lines and xenograft models. This phase I trial was designed to test the safety and tolerability of combining eribulin and everolimus in patients with metastatic TNBC. Methods The primary objective of this study was to evaluate the safety and toxicities of the combination. Patients with metastatic TNBC who had up to four lines of prior chemotherapies were enrolled. The combination of eribulin and everolimus was tested using three dosing levels: A1 (everolimus 5 mg daily; eribulin 1.4 mg/m2 days 1 and 8 every 3 weeks), A2 (everolimus 7.5 mg daily; eribulin 1.4 mg/m2, days 1 and 8 every 3 weeks), and B1 (everolimus 5 mg daily; eribulin 1.1 mg/m2 days 1 and 8 every 3 weeks). Results Twenty-seven patients with median age 55 years were enrolled. Among 8 evaluable patients who received dose level A1, 4 had dose-limiting toxicities (DLTs). Among 3 evaluable patients treated with dose level A2, 2 had DLTs. Among 12 evaluable patients who received dose level B1, 4 had DLTs. The DLTs were neutropenia, stomatitis, and hyperglycemia. Over the study period, 59% had a ≥ grade 3 toxicity, 44% had ≥ grade 3 hematologic toxicities, and 22% had grade 4 hematologic toxicities. The most common hematological toxicities were neutropenia, leukopenia, and lymphopenia. Thirty-three percent had grade 3 non-hematologic toxicities. The most common non-hematological toxicities were stomatitis, hyperglycemia, and fatigue. The median number of cycles completed was 4 (range 0–8). Among 25 eligible patients, 9 patients (36%) achieved the best response as partial response, 9 (36%) had stable disease, and 7 (28%) had progression. The median time to progression was 2.6 months (95% CI [2.1, 4.0]), and median overall survival (OS) was 8.3 months (95% CI [5.5, undefined]). Conclusion Eribulin 1.1 mg/m2 days 1 and 8 every 3 weeks with everolimus 5 mg daily was defined as the highest dose with acceptable toxicity (RP2D). The combination is safe, and efficacy is modest. A post hoc analysis showed that participants that used dexamethasone mouthwash stayed on treatment for one additional cycle. Trial registration ClinicalTrials.gov, NCT02120469. Registered 18 April 2014

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