Chemotherapy Regimens For Treatment Research Articles

Pediatric and Teen Ovarian Tissue Removed for Cryopreservation Contains Follicles Irrespective of Age, Disease Diagnosis, Treatment History, and Specimen Processing Methods.

Fertility preservation in a pediatric and teen female population is challenging because standard technologies of egg and embryo freezing may not be possible due to premenarcheal status. Ovarian tissue cryopreservation (OTC) with the intent of future ovarian tissue transplantation or in vitro follicle growth may be the only option to preserve fertility. The purpose of this study was to add to the general understanding of primordial follicle dynamics in young patients. First, the unique infrastructure of the Oncofertility Consortium National Physicians Cooperative (OC-NPC) is described, which simultaneously drives clinical fertility preservation and basic research to explore and expand the reproductive options for those in need. Then, the OC-NPC research resource is used to perform a histological evaluation of ovarian tissue from 24 participants younger than 18 years of age. Primordial follicles, which comprise the ovarian reserve, were observed in all participant tissues, irrespective of variables, including age, diagnosis, previous treatment history, tissue size, and tissue processing methods. Primordial follicles were present in ovarian tissue, even in participants who had a previous history of exposure to chemotherapy and/or radiation treatment regimens, which placed them at risk for iatrogenic infertility or premature ovarian failure. Primordial follicles were observed in ovarian tissue from all participants examined, despite population and tissue heterogeneity. These results increase the understanding of human follicle dynamics and support OTC as a promising fertility preservation modality in the young female population. Future studies to evaluate follicle quality within these tissues are warranted.

Applying a Model to Predict Neutropenia Risk in Patients With Cancer Using Electronic Data

Background/Aims: Granulocyte-colony stimulating factors (G-CSFs) are indicated to decrease the incidence of infections associated with chemotherapy-induced neutropenia (a severe reduction in white blood cells) in cancer patients receiving myelosuppressive chemotherapy. Severe neutropenia or febrile neutropenia occurs in 25–40% of treatment-naïve patients and are associated with increased infection rates, treatment delays, dose reductions, hospitalizations, deaths and increased costs. In addition to the chemotherapy treatment regimen, patient-specific factors influence neutropenic risk. Current guideline recommendations do not include a mechanism to quantify patient risk when determining need to G-CSF support. Studies report over- and underuse of G-CSF among those at low and high risk for neutropenia. A neutropenia risk model developed by Lyman et al. showed prior chemotherapy, relative dose intensity (RDI), abnormal liver and renal function, and low white cell count are major risk factors. We are testing the feasibility of using readily available clinical and administrative data from the HealthPartners electronic medical record and Oncology Treatment Module to apply the Lyman model to data from adult cancer patients receiving first cycle chemotherapy.

Cost-effectiveness analysis of three chemotherapy regimens for treatment of gastric cancer

Cost-effectiveness analysis of three chemotherapy regimens for treatment of gastric cancer

Role of ABC transporters in fluoropyrimidine-based chemotherapy response.

Since over 50 years, 5-fluorouracil (5-FU) is in use as backbone of chemotherapy treatment regimens for a wide range of cancers including colon, breast, and head and neck carcinomas. However, drug resistance and severe toxicities such as mucositis, diarrhea, neutropenia, and vomiting in up to 40% of treated patients often lead to dose limitation or treatment discontinuation. Because the oral bioavailability of 5-FU is unpredictable and highly variable, 5-FU is commonly administered intravenously. To overcome medical complications and inconvenience associated with intravenous administration, the oral prodrugs capecitabine and tegafur have been developed. Both fluoropyrimidines are metabolically converted intracellularly to 5-FU, which then needs metabolic activation to exert its damaging activity on RNA and DNA. The low response rates of 10-15% of 5-FU monotherapy can be improved by combination regimens of infusional 5-FU and leucovorin together with oxaliplatin (FOLFOX) or irinotecan (FOLFIRI), thereby increasing response rates to 30-40%. The impact of metabolizing enzymes in the development of fluoropyrimidine toxicity and resistance has been studied in great detail. In addition, membrane drug transporters, which are critical determinants of intracellular drug concentrations, may play a role in occurrence of toxicity and development of resistance against fluoropyrimidine-based therapy as well. This review therefore summarizes current knowledge on the role of drug transporters with particular focus on ATP-binding cassette transporters in fluoropyrimidine-based chemotherapy response.

Predictive model for risk of severe gastrointestinal toxicity following chemotherapy using patient immune genetics and type of cancer: a pilot study.

Severe chemotherapy-induced gastrointestinal toxicity (CIGT) is common and results in treatment delays, dose reductions, and potential premature treatment discontinuation. Currently, there is no diagnostic marker to predict CIGT. Proinflammatory cytokines, produced via toll-like receptor signaling, are key mediators of this toxicity. Hence, this pilot study investigated the association between immune genetic variability and severe CIGT risk. Genomic DNA from 34 patients (10 with severe CIGT) who had received 5-fluoruracil-based chemotherapy regimens was analyzed for variants of IL-1B, IL-2, IL-6, IL-6R, IL-10, TNF-a, TGF-b, TLR2, TLR4, MD2, MYD88, BDNF, CRP, ICE, and OPRM1. Multivariate logistic regression created a prediction model of severe CIGT risk. There were no significant differences between patients with and without severe CIGT with regards to age, sex, type of cancer, or chemotherapy treatment regimens. The prediction model of severe CIGT risk included TLR2 and TNF-a genetic variability and cancer type (colorectal and gastric). This prediction model was both specific and sensitive, with a receiver operator characteristic area under the curve of 87.3%. This is the first report of immune genetic variability, together with cancer type, being predictive of severe CIGT risk. These outcomes are being validated in a larger patient population.

Amelioration of cisplatin-induced experimental peripheral neuropathy by a small molecule targeting p75NTR

Cisplatin is an effective and widely used first-line chemotherapeutic drug for treating cancers. However, many patients sustain cisplatin-induced peripheral neuropathy (CIPN), often leading to a reduction in drug dosages or complete cessation of treatment altogether. Therefore, it is important to understand cisplatin mechanisms in peripheral nerve tissue mediating its toxicity and identify signaling pathways for potential intervention. Rho GTPase activation is increased following trauma in several models of neuronal injury. Thus, we investigated whether components of the Rho signaling pathway represent important neuroprotective targets with the potential to ameliorate CIPN and thereby optimize current chemotherapy treatment regimens. We have developed a novel CIPN model in the mouse. Using this model and primary neuronal culture, we determined whether LM11A-31, a small-molecule, orally bioavailable ligand of the p75 neurotrophin receptor (p75NTR), can modulate Rho GTPase signaling and reduce CIPN. Von Frey filament analysis of sural nerve function showed that LM11A-31 treatment prevented decreases in peripheral nerve sensation seen with cisplatin treatment. Morphometric analysis of harvested sural nerves revealed that cisplatin-induced abnormal nerve fiber morphology and the decreases in fiber area were alleviated with concurrent LM11A-31 treatment. Cisplatin treatment increased RhoA activity accompanied by the reduced tyrosine phosphorylation of SHP2, which was reversed by LM11A-31. LM11A-31 also countered the effects of calpeptin, which activated RhoA by inhibiting SHP2 tyrosine phosphatase. Therefore, suppression of RhoA signaling by LM11A-31 that modulates p75NTR or activates SHP2 tyrosine phosphatase downstream of the NGF receptor enhances neuroprotection in experimental CIPN in mouse model.

Aggressive variants of castration-resistant prostate cancer.

A subset of patients with advanced castration-resistant prostate cancer may eventually evolve into an androgen receptor (AR)-independent phenotype, with a clinical picture associated with the development of rapidly progressive disease involving visceral sites and hormone refractoriness, often in the setting of a low or modestly rising serum prostate-specific antigen level. Biopsies performed in such patients may vary, ranging from poorly differentiated carcinomas to mixed adenocarcinoma-small cell carcinomas to pure small cell carcinomas. These aggressive tumors often demonstrate low or absent AR protein expression and, in some cases, express markers of neuroendocrine differentiation. Because tumor morphology is not always predicted by clinical behavior, the terms "anaplastic prostate cancer" or "neuroendocrine prostate cancer" have been used descriptively to describe these rapidly growing clinical features. Patients meeting clinical criteria of anaplastic prostate cancer have been shown to predict for poor prognosis, and these patients may be considered for platinum-based chemotherapy treatment regimens. Therefore, understanding variants within the spectrum of advanced prostate cancer has important diagnostic and treatment implications.

Patterns of chemotherapy (CT) use in a population-based US-wide cohort of patients (pts) with metastatic pancreatic cancer (MPC).

4131 Background: Few population studies have examined the frequencies and durations of specific CT treatment regimens in MPC. Methods: We assessed 3,796 consecutive MPC pts who received CT between Jan 2005 and Aug 2013 at academic, private and community hospital-based practices participating in a US-wide CT order entry system that captures pt, provider and treatment data. Multivariate analyses of prospectively recorded pt and provider characteristics identified predictors of specific therapeutic approaches. Results: Among all pts, median age was 70; 55% male. In 1st-line CT, 48% of pts received gemcitabine (GEM) monotherapy, 16% received a GEM-based doublet (incl. GEM + nab-paclitaxel [NAB-P]), 9% received fluoropyrimidine (FU) + oxaliplatin (OX) + irinotecan (FOLFIRINOX), 9% received FU monotherapy, and 5% received FU + OX (FOLFOX). The remaining 13% received other regimens. GEM monotherapy use peaked at 58% in 2009 but declined to 28% in 2013. FOLFIRINOX use emerged in 2010 with 4% usage and peaked at 2...

Lower Ras expression as an independent predictor of patient outcomes in lung cancer treated with bevacizumab plus chemotherapy

The objective of this study was to analyze the predictive roles of VEGF/KDR/Ras/MAPK gene expression in patients with advanced non-small-cell lung cancer (NSCLC) treated with bevacizumab plus chemotherapy. Twenty-five patients participating in an open-label phase IV trial (SAiL, MO19390) with available tumor tissues were analyzed. The mRNA expression levels of VEGF, kinase insert domain receptor (KDR), Ras, and mitogen-activated protein kinase (MAPK) in tumor tissues were detected using real-time quantitative PCR methods. The relationships between gene expression and disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were assessed. Patients with lower Ras expression had a longer PFS and OS than patients with higher expression (median PFS, 9.9 vs 5.5 months, χ(2)=3.944, P=0.047; OS, 19.3 vs 7.1 months, χ(2)=9.384, P=0.002). The PFS and OS of patients with lower and higher MAPK expression exhibited a marginal and significant difference (median PFS, 9.9 vs 5.5 months, χ(2)=3.464, P=0.063; OS, 19.3 vs 9.7 months, χ(2)=5.298, P=0.021), respectively. Multivariate analyses using Cox's proportional hazards model showed that Ras is an independent predictor of OS (χ(2)=9.384, P=0.002). No differences in DCR were found according to Ras expression level. The results indicate that Ras is an independent predictor of OS. Thus, patients with lower Ras expression are most likely to benefit from bevacizumab plus chemotherapy treatment regimen. Patients with higher levels of Ras should receive other inhibitors that target Ras. The results also suggest that gene therapies that decrease RAS expression combined with bevacizumab may improve lung cancer treatment. Although there is a very important implication to patient selection in the target therapy, the data in this study are very preliminary owing to the too small sample size. Therefore, further research involving large numbers of patients and a prospective assessment of low and high RAS mRNA expressions getting the same treatments need to be done before conclusions can be made.

Shenqifuzheng injection combined with chemotherapy in the treatment of advanced gastric cancer: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of Shenqifuzheng (SQFZ) injection combined with chemotherapy in the treatment of advanced gastric cancer. We conducted an electronic search by using PubMed, EMBASE, ASCO, ESMO and Chinese National Knowledge Infratructure (CNKI), databases. The randomized controlled trials about Shenqifuzheng injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced gastric cancer were reviewed and collected. Pooled odds ratio (OR) for the response rate and KPS improvement were calculated using the software MetaAnalyst 3.1. Fifteen trials met our inclusion criteria and finally included in this meta-analysis. The objective response rate (ORR) in patients treated with Shenqifuzheng injection combined with chemotherapy was much higher than that of chemotherapy only (OR = 1.66, 95% CI: 1.20-2.29) with statistical significance (P < 0.05). The pooled data showed the combined treatment can significant increase the Karnofsky score (KPS) compared with the chemotherapy only (OR = 3.74, 95% CI: 2.66-5.27 (P < 0.05). SQFZ injection combined with chemotherapy treatment regimen can improve the clinical efficacy and performance status in patients with advanced gastric cancer compared with chemotherapy alone.

Utility Of Routine Left Ventricular Ejection Fraction (LVEF) Measurement Prior To Administration Of Anthracycline-Based Chemotherapy In Patients With Diffuse Large B-Cell Lymphoma (DLBCL)

Anthracycline-based chemotherapy regimens are considered the gold standard for treating patients with DLBCL. Prior to administration of chemotherapy, LVEF is routinely measured, usually by multiple-gated acquisition (MUGA) scans or echocardiography, as a screening tool for detecting asymptomatic left ventricular dysfunction. LVEF screening is recommended by the National Comprehensive Cancer Network clinical practice guidelines, is endorsed by the American Heart Association and the American College of Cardiology, appears on Federal Drug Administration-approved labeling guidelines, and is often required for patients to participate in US cancer cooperative group clinical trails. However, despite these recommendations, evidence supporting the utility of LVEF measurement prior to administration of anthracycline-based chemotherapy in patients with DLBCL is lacking (Conrad, J Oncol Pract 2012).The most common chemotherapy regimen currently administered to DLBCL patients is rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients with stage III or IV DLBCL typically receive 6 to 8 cycles of R-CHOP, with cumulative doses of doxorubicin ranging from 300 - 400 mg/m2. Cumulative doses of doxorubicin greater than 400 mg/m2have been associated with an increased risk of congestive heart failure (CHF) (Von Hoff, Ann Intern Med 1979).We are performing a retrospective analysis of approximately 325 patients with DLBCL who received treatment at Virginia Mason Medical Center from 2001-2011. Our objectives include the following: (1) to determine whether LVEF was measured by echocardiogram or MUGA scan prior to administration of anthracycline-based chemotherapy, (2) to establish whether the chemotherapy treatment regimen was modified based on LVEF values, and (3) to document the incidence of CHF in patients with DLBCL who did receive anthracycline-based chemotherapy.Patients were identified through a search of the Virginia Mason Cancer Registry. Specific data currently being collected through chart review include the following: age at diagnosis; Ann Arbor lymphoma stage; type of chemotherapy given; cumulative doxorubicin dose administered (mg/m2); LVEF measurement and modality used to assess LVEF; and incidence of CHF. We are also recording the number of CHF risk factors that patients possess, including male sex, obesity, hypertension, hyperlipidemia, prior cardiac disease, diabetes mellitus, smoking history, prior chemotherapy, radiation to the chest area, and other cardio-toxic exposures. Statistical analyses will include a Fischer's exact or Chi-squared test to compare study groups and a Wilcoxon rank sum test to compare the number of CHF risk factors. A P value of less than 0.05 will be used to determine if an association is significant.In a preliminary sample of DLBCL patients (n = 50), 28 are men (56%). LVEF was measured in 40 patients (80%) prior to initiation of chemotherapy using echocardiogram (95%) and MUGA scan (5%). LVEF values were normal (55 – 75%) in 36 patients (90%), low (< 55%) in 3 patients (8%), and unknown in 1 patient (2%). Of the 36 patients with normal LVEF values, 30 received CHOP or R-CHOP regimens (83%), 2 received non-anthracycline chemotherapy (5%), 1 was treated by surgical excision alone (3%), 2 received no treatment (6%), and 1 patient's treatment was unknown (3%). Of the 3 patients with initial low screening LVEF values, none had a prior history of CHF and all received R-CHOP (100%). Three patients did have CHF prior to treatment; however, only one received CHOP therapy. Of our initial 50 patients, 31 (62%) are alive and 2 (4%) were lost to follow-up. CHF was listed as a major contributor of death in 3 patients (6%). The median number of CHF risk factors did not differ significantly between patients who did develop CHF post-treatment and those who did not (4 vs. 2, P = 0.133).Our preliminary results suggest that the decision to administer an anthracycline-based chemotherapy regimen was not directly affected by echocardiogram or MUGA scan results. If these findings are reinforced at completion of our chart review, it may challenge the existing policy of routinely screening patients with DLBCL with echocardiograms or MUGA scans prior to initiation of treatment. Disclosures:No relevant conflicts of interest to declare.

Usability evaluation of HemOnc.org, a collaborative online hematology/oncology reference.

244 Background: With an ever-growing body of medical knowledge, open access to accurate information is critical to quality care. HemOnc.org is a free online collaborative wiki created by health care professionals to record, access, and share information about chemotherapy treatment regimens and drugs. As of June 2013, the site contains referenced information for 931 regimens and 316 drugs. The site receives &gt;7,000 visits/mo and has had &gt;425,000 total page views from around the world (29% from outside the United States). We conducted a survey to evaluate the usability of the site. Methods: The survey was open May 1 to May 31, 2013. Participants were invited by site announcements, social media, and emails to hematology/oncology fellowship programs. Usability was assessed by 100-point scales (higher = better). Other data were collected via multiple choice questions with optional free text entry. Results: There were 139 respondents; demographics are shown in the Table. They felt that the site was useful (median 90, interquartile range (IQR) 76-99.5), usable (median 85, IQR 69-98), and recommendable to colleagues (median 87, IQR 72-99). Although 100% of users reported using other references (e.g. textbooks), 70.5% reported accuracy issues with these references (Table). Conclusions: HemOnc.org provides a new way to access and share curated knowledge. No resource is 100% accurate, but the open and transparent nature of the site allows users to actively correct errors and inconsistencies. Feedback has been positive, suggesting that an unmet need for information is being satisfied. Our goal is to improve collaboration, foster greater knowledge sharing among the oncology community, and improve quality of care through open dissemination of accurate information to a widespread audience. [Table: see text]

Automated synthesis and visualization of a chemotherapy treatment regimen network.

Cytotoxic treatments for cancer remain highly toxic, expensive, and variably efficacious. Many chemotherapy regimens are never directly compared in randomized clinical trials (RCTs); as a result, the vast majority of guideline recommendations are ultimately derived from human expert opinion. We introduce an automated network meta-analytic approach to this clinical problem, with nodes representing regimens and edges direct comparison via RCT(s). A chemotherapy regimen network is visualized for the primary treatment of chronic myelogenous leukemia (CML). Node and edge color, size, and opacity are all utilized to provide additional information about the quality and strength of the depicted evidence. Historical versions of the network are also created. With this approach, we were able to compactly compare the results of 17 CML regimens involving RCTs of 9700 patients, representing the accumulation of 45 years of evidence. Our results closely parallel the recommendations issued by a professional guidelines organization, the National Comprehensive Cancer Network (NCCN). This approach offers a novel method for interpreting complex clinical data, with potential implications for future objective guideline development.

MR elastography derived shear stiffness-a new imaging biomarker for the assessment of early tumor response to chemotherapy

The overall goal is to develop magnetic resonance elastography derived shear stiffness as a biomarker for the early identification of chemotherapy response, allowing dose, agent type and treatment regimen to be tailored on a per patient basis, improving therapeutic outcome and minimizing normal tissue toxicity. The specific purpose of this study is to test the feasibility of this novel biomarker to measure the treatment response in a well-known chemotherapy model. Tumors were grown in the right flank of genetically modified mice by subcutaneous injection of DoHH2 (non-Hodgkin's lymphoma) cells. Magnetic resonance elastography was used to quantify tumor stiffness before and after injection of a chemotherapeutic agent or saline. Histological tests were also performed on the tumors. A significant decrease (P < 0.0001) in magnetic resonance elastography-derived tumor shear stiffness was observed within 4 days of chemotherapy treatment, while no appreciable change was observed in saline-treated tumors. No significant change in volume occurred at this early stage, but there were decreased levels of cellular proliferation in chemotherapy-treated tumors. These results demonstrate that magnetic resonance elastography-derived estimates of shear stiffness reflect an initial response to cytotoxic therapy and suggest that this metric could be an early and sensitive biomarker of tumor response to chemotherapy.

Use of VEGF expression to predict for first-line treatment chemotherapy regimen in metastatic colorectal cancer.

e14695 Background: In metastatic colorectal cancer treatment more successful results are achieved by adding anti-angiogenic therapy to the chemotherapy. Over expression of VEGF in colorectal cancer is known to be a poor prognosis factor but its effects on designating the therapy is not clear. In this study, results of the patients receiving FOLFIRI + Bevacizumab or XELOX + Bevacizumab were compared for VEGF expression. Methods: VEGF was assessed immunohistochemically in primary tumors of the 53 metastatic colorectal cancers. Severity and conformity of VEGF expression was evaluated. Results were used to assess the association with the therapy response, progression free survival (PFS) and overall survival (OS). Results: The median age of the patients was 55 (range, 32-79). In combination with bevacizumab 38 patients received FOLFIRI and 15 patients received XELOX. In 30 patients (57%) there was a strong expression of VEGF and in 23 patients (23%) the expression was weak. In the high VEGF expression group, PFS was 11 months in FOLFIRI receiving patients and 8 months in XELOX receiving ones but in low expression group PFS was 8 months in patients receiving either one of the two treatment protocols. In high expression group, PFS in FOLFIRI-bevacizumab combination receiving patients was different and this difference was statistically significant (p=0.009). Overall survival in FOLFIRI receiving patients with high VEGF expression was 26 months and with low VEGF expression it was 16 months (p=0.04). Median OS was not reached in the XELOX receiving patient group. FOLFIRI regime clinical benefit was 58% in high VEGF expression group whilst it was 34% in low expression group. This difference was not statistically significant but it was close to the significance threshold (p=0.06). There was no association between the therapy responses and VEGF expression of the 15 patients who received XELOX. Conclusions: There is no difference in efficacy between the first line chemotherapy regimens of the metastatic colorectal cancer. In this study, in metastatic colorectal patients with over expressed VEGF first line FOLFIRI-bevacizumab combination led to better response and survival rates.

The predictive role of phosphatase and tensin homolog (PTEN) loss, phosphoinositol-3 (PI3) kinase (PIK3CA) mutation, and PI3K pathway activation in sensitivity to trastuzumab in HER2-positive breast cancer: a meta-analysis

Objective:Phosphatase and tensin homolog (PTEN) loss or activating mutations of phosphoinositol-3 (PI3) kinase (PIK3CA) may be related to trastuzumab resistance in in vitro studies; however, this issue in clinical studies is controversial. Therefore, we conducted a meta-analysis to assess the association between PTEN loss, PIK3CA mutation and the efficacy of trastuzumab-based treatment in HER2-positive breast cancer patients.Methods:A computerized search was performed through the PubMed database, the online proceedings of the American Society of Clinical Oncology Annual Meetings, the San Antonio Breast Cancer Symposium and the International St. Gallen Breast Cancer Conference. Ten eligible studies including 1889 cases were identified.Results:In HER2-positive locally advanced breast cancer patients, neither PTEN loss, PIK3CA mutation nor PI3K activation was associated with the response rate of trastuzumab-based neoadjuvant treatment (PTEN loss: RR = 0.687, 95% CI: 0.439–1.074, P = 0.099; PIK3CA mutation: RR = 1.114, 95% CI: 0.453–2.735, P = 0.814; PI3K activation: RR = 0.787, 95% CI: 0.417–1.484, P = 0.459; RR = 0.772, 95% CI: 0.387–1.539, P = 0.462). In HER2-positive early stage breast cancer patients, PTEN loss was not associated with the disease-free survival (DFS) rate of trastuzumab-based adjuvant treatment (HR = 1.096, 95% CI: 0.706–1.700, P = 0.684). In HER2-positive recurrent or metastatic breast cancer patients, PTEN loss was significantly correlated with poorer efficacy of trastuzumab-based salvage treatment (RR = 0.682, 95% CI: 0.550–0.846, P = 0.000).Conclusions:In HER2-positive recurrent or metastatic breast cancer patients PTEN loss might indicate resistance to trastuzumab-based salvage treatment. Due to the small sample size and the considerable heterogeneity in the chemotherapy treatment regimens, further research is needed to clarify the association between PTEN loss, PIK3CA mutation and the efficacy of trastuzumab-based treatment in neoadjuvant and adjuvant settings.

Abstract 5035: Stable transfection of the osteosarcoma cell line SaOs2, genetically transformed MSCs and osteoblasts with insulin-like growth factor 2 receptor.

Abstract Osteosarcoma (OS) is the most commonly seen primary malignant bone tumor in children and adolescents. With neo-adjuvant chemotherapy and other treatment regimens developed, event-free survival has increased to 70%, but the prognosis remains poor for those patients with unresectable or metastatic tumors or less responsive tumors. Insulin-like growth factor 2 (IGF2) and its receptor (IGF2R) are known to be over-expressed in several cancers including OS and have roles in regulating cellular growth and proliferation. Although IGF2R is thought to be a tumor suppressor, the research results in different experimental systems are variable. Our recent studies have demonstrated that IGF2R is consistently over-expressed, relative to other known transmembrane receptors on the cell surface across, 4 standard and 10 patient-derived OS cell lines. To further elucidate the effects of IGF2R in OS, the OS cell line SaOS2 and two cell lines which were genetically transformed, as follows; mesenchymal stem cells (MSC) and osteoblasts (OB) with human telomerase reverse transcriptase and SV40Tag (MSC-TS and OB-TS) were transformed with IGF2R by lentiviral transfection. Drug resistant colonies were picked up 21 days after selection to obtain stably transfected SaOS2, MSC-TS, and OB-TS cell lines now named, SaI, MSC-TSI and OB-TSI, respectively. After cloning, the highest and the lowest IGF2R expression clones were selected from these different cell lines via real-time PCR and western blot for further analysis. The comparison between the lines and characterizations are underway. Initial results suggest introduction of IGF2R changes the phenotype by enhancing cellular motility. Further studies will be presented and include the following: 1) cell proliferation assays, 2) motility and migration assays, 3) subcutaneous tumorigenicity assays, 4) expression profiling, and 5) differentiation assays. In the context of osteosarcoma introduction of IGF2R enhances motility, which is unexpected given prior expectations based on the non-signaling nature of this receptor. Citation Format: Huayi Qu. Stable transfection of the osteosarcoma cell line SaOs2, genetically transformed MSCs and osteoblasts with insulin-like growth factor 2 receptor. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5035. doi:10.1158/1538-7445.AM2013-5035

The Effect of the APPRISE Mandate on Use of Erythropoiesis-Stimulating Agents and Transfusion Rates in Patients With Ovarian Cancer Receiving Chemotherapy

Objective Erythropoiesis-stimulating agents (ESAs) support chemotherapy-induced anemia in patients with epithelial ovarian cancer (EOC). In response to research demonstrating that ESAs increase tumor growth and shorten survival, the Food and Drug Administration mandated the new APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe use of ESAs) guidelines for consenting patients before ESAs administration. We sought to quantify the change in ESA and red blood cell (RBC) transfusion use after the APPRISE mandate was instituted. Methods/Materials After institutional review board approval, a retrospective chart review compared patients with EOC undergoing chemotherapy before and after the APPRISE mandate. Abstracted data included patient demographics, chemotherapy treatment status and regimen, and number of patients requiring ESAs or RBCs. A cost savings analysis was also performed. Results Eighty-four patients who underwent 367 cycles of chemotherapy after the APPRISE guidelines were compared with a matched set of 88 patients receiving 613 cycles of chemotherapy before the APPRISE guidelines. There were no statistically significant differences between the groups. Most patients had advanced stage disease and received primary taxane-/platinum-based chemotherapy. Of 88 patients, 45 (51%) in the pre-APPRISE group received a total of 196 ESA injections compared with 0 patients in the post-APPRISE group. Red blood cell transfusion in the post-APPRISE group was similar to that in the pre-APPRISE group (8.3% vs 14.8%, P = 0.28). Omission of ESAs in the post-APPRISE group resulted in a roughly $700,000 savings in billable charges. Conclusions In our institution, the APPRISE guidelines have resulted in complete cessation of the use of ESAs in patients with primary or recurrent EOC, resulting in considerable cost savings. Importantly, RBC transfusion rates did not significantly increase after the guidelines were imposed.

The Effect of the APPRISE Mandate on Use of Erythropoiesis-Stimulating Agents and Transfusion Rates in Patients With Ovarian Cancer Receiving Chemotherapy

Erythropoiesis-stimulating agents (ESAs) support chemotherapy-induced anemia in patients with epithelial ovarian cancer (EOC). In response to research demonstrating that ESAs increase tumor growth and shorten survival, the Food and Drug Administration mandated the new APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe use of ESAs) guidelines for consenting patients before ESAs administration. We sought to quantify the change in ESA and red blood cell (RBC) transfusion use after the APPRISE mandate was instituted. After institutional review board approval, a retrospective chart review compared patients with EOC undergoing chemotherapy before and after the APPRISE mandate. Abstracted data included patient demographics, chemotherapy treatment status and regimen, and number of patients requiring ESAs or RBCs. A cost savings analysis was also performed. Eighty-four patients who underwent 367 cycles of chemotherapy after the APPRISE guidelines were compared with a matched set of 88 patients receiving 613 cycles of chemotherapy before the APPRISE guidelines. There were no statistically significant differences between the groups. Most patients had advanced stage disease and received primary taxane-/platinum-based chemotherapy. Of 88 patients, 45 (51%) in the pre-APPRISE group received a total of 196 ESA injections compared with 0 patients in the post-APPRISE group. Red blood cell transfusion in the post-APPRISE group was similar to that in the pre-APPRISE group (8.3% vs 14.8%, P = 0.28). Omission of ESAs in the post-APPRISE group resulted in a roughly $700,000 savings in billable charges. In our institution, the APPRISE guidelines have resulted in complete cessation of the use of ESAs in patients with primary or recurrent EOC, resulting in considerable cost savings. Importantly, RBC transfusion rates did not significantly increase after the guidelines were imposed.

Phase II Study of Induction Cisplatin and Irinotecan Followed by Concurrent Carboplatin, Etoposide, and Thoracic Radiotherapy for Limited-Stage Small-Cell Lung Cancer, CALGB 30206

We sought to determine the efficacy of using both irinotecan- and etoposide-containing regimens sequentially for patients with untreated limited-stage small-cell lung cancer. Patients with untreated, measurable, limited-stage small-cell lung cancer with performance status 0 to 2, and adequate organ function were eligible. Treatment consisted of induction with cisplatin 30 mg/m and irinotecan 65 mg/m intravenously on day 1 and 8, every 21 days for two cycles. Beginning day 43, daily chest irradiation to 70 Gy was administered concurrently with carboplatin area under curve 5 on day 1, and etoposide 100 mg/m on days 1 to 3, every 21 days for three cycles. The primary objective was to differentiate between 45% and 60% 2-year survival. Two induction cycles were delivered to 72 of 75 eligible patients (96%) and all planned treatment was delivered to 59 patients (79%). Cisplatin and irinotecan induction chemotherapy resulted in complete responses in 7% and partial responses in 64% (response rate 71%, 95% confidence interval [CI], 59%-81%). The best response to all therapy included 88% complete or partial responses (95% CI, 78%-94%). With median follow-up of 57 months, the median progression-free survival and overall survival are 12.6 (95% CI, 9.4-14.7) and 18.1 months (15.8-22.9), respectively. The 1- and 2-year survival was 69% and 31%, respectively. Frequent (>20%) grade 3 and 4 toxicities were neutropenia in 84%, hemoglobin in 36%, platelets in 51%, esophagitis in 22%, and dehydration in 24%. There were no fatal toxicities. This treatment regimen of irinotecan-cisplatin induction chemotherapy followed by 70 Gy concurrent radiation and etoposide-carboplatin had tolerable toxicity but did not meet the preplanned 2-year survival target for further development.