Treatment patterns in metastatic colorectal cancer (mCRC) in Slovakia.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14700-e14700
Author(s):  
Tomas Salek ◽  
Peter Pichna

e14700 Background: CRC is one of the most frequent malignant diseases in Slovakia. Slovakia with approximately 5 million inhabitants is country with the highest incidence of CRC in Europe, and there is a focus on CRC treatment within Slovak healthcare system. Methods: Between March 2012 and June 2012 we made a survey in the vast majority of hospital medical oncology departments and outpatient cancer clinics /93 facilities- it comprises approximately 95 % of Slovak departments and clinics treating metastatic CRC/. Data obtained during this 4months period were then multiplied by 3, and that gave us the approximate yearly data. (We reviewed data from 532 patients during four months period.) Results: 670 newly diagnosed mCRC patients (pts) (38%) were treated with chemotherapy alone in the first line, 867 pts (48%) with chemotherapy plus biologics and 231 pts (13%) were treated with best supportive care only. 87% of our newly diagnosed mCRC pts were treated with first line therapy, 37% with second line therapy and 25% with third and later lines of treatment. 42% of pts had KRAS status examined with following results: 44% KRAS wild type, 50.4% KRAS mutated and 5.6% status unknown. Conclusions: We conclude that in Slovakia we have similar patterns of mCRC treatment like in other Middle European countries and high percentage of pts in the first line is treated with biologic therapy.

2021 ◽  
Vol 10 (21) ◽  
pp. 5166
Author(s):  
Chih-Chien Wu ◽  
Chao-Wen Hsu ◽  
Meng-Che Hsieh ◽  
Jui-Ho Wang ◽  
Min-Chi Chang ◽  
...  

Although several sequential therapy options are available for treating patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), the optimal sequence of these therapies is not well established. A systematic review and meta-analysis of 13 randomized controlled trials and 4 observational studies were performed, resulting from a search of the Cochrane Library, PubMed, and Embase databases. Overall survival (OS) did not differ significantly in patients with RAS-WT failure who were administered a second-line regimen of changed chemotherapy (CT) plus anti-epidermal growth factor receptor (EGFR) versus only changed CT, changed CT plus bevacizumab versus changed CT plus anti-EGFR, or changed CT versus maintaining CT plus anti-EGFR after first-line therapy with CT, plus bevacizumab. However, OS was significantly different with a second-line regimen that included changed CT plus bevacizumab, versus only changing CT. Analysis of first-line therapy with CT plus anti-EGFR for treatment of RAS-WT mCRC indicated that second-line therapy of changed CT plus an anti-EGFR agent resulted in better outcomes than changing CT without targeted agents. The pooled data study demonstrated that the optimal choice of second-line treatment for improved OS was an altered CT regimen with retention of bevacizumab after first-line bevacizumab failure. The best sequence for first-to-second-line therapy of patients with RAS-WT mCRC was cetuximab-based therapy, followed by a bevacizumab-based regimen.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S680-S681
Author(s):  
Carly Heck ◽  
Judith Martin ◽  
Marcia Kurs-Lasky

Abstract Background Background: Antibiotic resistance is a major public health concern. A modifiable intervention is outpatient antibiotic stewardship. The goal of this study was to review the electronic health records (EHR) of children diagnosed with community acquired pneumonia (CAP) to compare patients who received non-guideline concordant therapy with those prescribed recommended therapy. Methods Methods: This was a retrospective chart review of 300 children (6 months to 6 years old) with an outpatient diagnosis of CAP between July 2017 and June 2019. 45 Children’s Hospital of Pittsburgh (CHP) and UPMC Children’s Community Pediatrics (CCP) practices were included. CHP practices are academic-based with trainees involved in visits, while CCP practices do not include trainees. First-line recommended therapy was defined as amoxicillin, second-line therapy as azithromycin or amoxicillin-clavulanate, and all other prescriptions were defined as other. Patients prescribed first-line therapy were compared to patients with second-line therapy or other. If first-line therapy was not prescribed, the EHR was manually reviewed for justification. If drug allergy was listed, the medication allergy and type of reaction were recorded. Results Results: In this study the minority of children (43%) were prescribed first-line therapy. This group was younger (57 vs. 63 months of age), more likely to be Non-white (80%), and seen at the CHP locations than those prescribed non-guideline concordant therapy. The average symptom duration was shorter, heart rate and respiratory rate were higher and the presence of fever was more common in the first-line therapy group. Justification for non-guideline therapy was most often reported as to provide coverage for atypical organisms. The most common drug allergy recorded was amoxicillin, and urticaria with unknown timing was the most common type of reaction. Demographics Comparison Results Justification for Second-line / Other Therapy and Drug Allergy Results Conclusion This project observed a high proportion of children being prescribed non-guideline concordant therapy for a diagnosis of CAP. Age, race, practice location, and severity of illness measures showed a statistically significant difference between groups. This study highlights the importance of education which reviews the current guidelines and the most likely pathogens for children with CAP. Disclosures All Authors: No reported disclosures


2004 ◽  
Vol 22 (7) ◽  
pp. 1209-1214 ◽  
Author(s):  
Axel Grothey ◽  
Daniel Sargent ◽  
Richard M. Goldberg ◽  
Hans-Joachim Schmoll

Purpose Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. Materials and Methods We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. Results The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P = .0008) but not with the percentage of patients who received any second-line therapy (P = .19). In addition, the use of combination protocols as first-line therapy was associated with a significant improvement in median survival of 3.5 months (95% CI, 1.27 to 5.73 months; P = .0083). Conclusion Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.


2018 ◽  
Vol 9 (22) ◽  
pp. 4092-4098
Author(s):  
Shigeyoshi Iwamoto ◽  
Hiromichi Maeda ◽  
Shoichi Hazama ◽  
Koji Oba ◽  
Naoko Okayama ◽  
...  

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Ali McBride ◽  
Daniel O. Persky

Introduction: The choice of initial therapy in follicular lymphoma can be a key determinant in future therapy, as irreversible toxicities with first line regimens can impact the patient's ability to tolerate future treatment. Minimizing drug exposure will result in less frequent occurrence of significant adverse events and associated treatment costs. In the era of COVID-19 pandemic, there is additional benefit to minimizing the number of patient visits and hospital admissions. Limited information exists related to the outcomes and associated costs of existing treatment sequences. Additionally, treatment administration at different types of clinical sites results in varied reimbursement models, making informed evaluation of clinical and financial evidence challenging. Methods: The current study applies a budget impact model methodology in order to describe the associated impact of treatment selection and sequencing on outcomes and costs in the treatment of relapsed or refractory low-grade follicular lymphoma in first line therapy followed by Consolidation and also in first line therapy to second line therapy. Key model inputs included: Number of treatment cycles, number of days a treatment was received, duration of response (DOR), rate of side effects and associated costs, and total treatment costs, including drugs, medical treatment, laboratory testing and adverse event costs. Treatment outcomes were based on the published literature that summarized the overall response rate, median DOR, and toxicity. Treatment regimen costs were evaluated based on payer pricing, Wholesale Acquisition Cost (WAC), Average Selling Price (ASP) and Average Wholesale Price (AWP) and modified to adjust for weight-based dosing and negotiate payer reimbursement rates. Associated medical costs for medical treatment and supportive care were estimated using current Medicare fee schedule rates. Included were seven options for first line therapy of follicular lymphoma from 2020 NCCN Guidelines - (Bendamustine + rituximab (BR); Bendamustine + Obinutuzumab (OB); CHOP rituximab (RCHOP); CHOP + Obinutuzumab (OCHOP); CVP+ rituximab (RCVP); CVP + Obinutuzumab (OCVP); Lenalidomide + rituximab (R2)), followed by three for Consolidation (Rituximab maintenance (RM); Obinutuzumab maintenance (O); Radioimmunotherapy (RIT with 90 Y-ibritumomab tiuxetan (Y90-IT, Zevalin)) and three Second Line therapy options (RIT; Lenalidomide only; Lenalidomide + Obinutuzumab (LO)). Results: The treatment sequence of first line BR followed by Consolidation with RIT Y90 (Zevalin) had the longest predicted DOR (2586 days). The associated treatment sequence costs were $212,485 for BR followed by Y90-IT, compared with $233, 388 for BR followed by rituximab maintenance, which had a predicted DOR of 2478 days. The predicted DOR for treatment sequences starting with OCHOP, OCVP and RCHOP and followed by RIT with Y90-IT was approximately 1000 days less than BR followed by Y90-IT for a cost difference of $4,421, $12,914 and $25,826, respectively. The treatment sequence of first line BR followed by Second Line RIT Y90-IT had the second longest predicted DOR of 2586 days at costs of $212,485, compared to 2778 days for BR followed by LO, at a total sequence costs of $796,695. Conclusion: The use of Y90-IT in Consolidation or Second Line treatment demonstrated desired patient outcomes at one of the lowest cost profiles. Additionally, Y90-IT administration can be completed in only two clinic visits, reducing patient travel and contact, improving safety in an era of COVID-19 precautionary measures and reducing cost. Figure 1. Duration of Response and Total Sequence Costs for Twelve First Line to Consolidation and First Line to Second Line Treatment Regimens. Disclosures McBride: Merck: Speakers Bureau; Coherus BioSciences: Consultancy, Speakers Bureau; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy; MorphoSys: Consultancy; Sandoz: Consultancy.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7007-7007
Author(s):  
Jessica K. Altman ◽  
Jamie Koprivnikar ◽  
James K. McCloskey ◽  
Vamsi Kota ◽  
Olga Frankfurt ◽  
...  

7007 Background: Aspacytarabine (BST-236) is a prodrug of cytarabine, the backbone of acute myeloid leukemia (AML) standard of care chemotherapy, associated with toxicity which precludes its administration in older patients and patients with comorbidities. Aspacytarabine is inactive in its intact prodrug form until cytarabine is gradually released at pharmacokinetics which decrease the systemic exposure to peak toxic cytarabine levels, resulting in reduced systemic toxicity and relative sparing of normal tissues, enabling therapy with high cytarabine doses to patients otherwise unfit to receive it. Methods: A phase 2b open-label, single-arm study to evaluate the efficacy and safety of aspacytarabine as a first-line single-agent therapy in newly-diagnosed AML patients unfit for standard chemotherapy (NCT03435848). Aspacytarabine is administrated at 4.5 g/m2/d (containing 3 g/m2/d cytarabine) in 1-2 induction and 1-3 consolidation courses, each consisting of 6 daily 1-hour infusions. Patients with secondary AML, prior hypomethylating agent (HMA) therapy, and therapy-related AML, are eligible. Results: To date, in the ongoing study, 46 newly-diagnosed AML patients unfit for standard chemotherapy (median age 75 years) were treated with aspacytarabine and completed 1-4 courses of 4.5 g/m2/d aspacytarabine, including 26 patients (63%) with de novo AML and 17 (37%) with secondary AML. Six patients (13%) were previously treated with HMA (median 12 courses). The baseline median bone marrow blasts was 52%, and 54% and 29% of patients had adverse or intermediate European LeukemiaNet (ELN) score, respectively. Twenty (43%) patients had ECOG 2. Aspacytarabine is safe and well-tolerated in repeated-course administration. Grade > 2 drug-related adverse events include mainly hematological events and infections. The 30-day mortality rate is 11%. Of 43 patients evaluable for efficacy analysis to date, 15 patients (35%) reached a complete remission (CR) following 1 (13 patients) or 2 (2 patients) induction courses, all with complete hematological recovery (median 27.5 days, range 22-39 days). The CR rates in de novo AML patients and patients with adverse ELN score are 46% and 33%, respectively. Of the 11 patients evaluable to date for minimal residual disease (MRD) flow cytometry test, 8 are MRD negative (73%). While aspacytarabine treatment consists of a limited number of courses, median duration of response and median overall survival for responders are not reached at 12 and 24 months, respectively (end of follow up). Updated results will be presented at the meeting. Conclusions: The cumulative clinical data suggest that aspacytarabine, a time-limited single-agent treatment, is safe and efficacious as a first-line therapy for patients who are unfit for intensive chemotherapy, which may establish it as a new tolerable AML chemotherapy backbone. Clinical trial information: NCT03435848.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hironaga Satake ◽  
Koji Ando ◽  
Eiji Oki ◽  
Mototsugu Shimokawa ◽  
Akitaka Makiyama ◽  
...  

Abstract Background FOLFOXIRI plus bevacizumab is used as a first-line therapy for patients with unresectable or metastatic colorectal cancer. However, there are no clear recommendations for second-line therapy after FOLFOXIRI plus bevacizumab combination. Here, we describe our planning for the EFFORT study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Methods EFFORT is an open-label, multicenter, single arm phase II study to evaluate whether a FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Patients with unresectable or metastatic colorectal cancer who received FOLFOXIRI plus bevacizumab as a first-line therapy will receive aflibercept and FOLFIRI (aflibercept 4 mg/kg, irinotecan 150 mg/m2 IV over 90 min, with levofolinate 200 mg/m2 IV over 2 h, followed by fluorouracil 400 mg/m2 bolus and fluorouracil 2400 mg/m2 continuous infusion over 46 h) every 2 weeks on day 1 of each cycle. The primary endpoint is progression-free survival (PFS). To achieve 80% power to show a significant response benefit with a one-sided alpha level of 0.10, assuming a threshold progression-free survival of 3 months and an expected value of at least 5.4 months, we estimated that 32 patients are necessary. Secondary endpoints include overall survival, overall response rate, safety, and exploratory biomarker analysis for differentiating anti-VEGF drug in 2nd-line chemotherapy for unresectable or metastatic colorectal cancer. Discussion This is the first study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for unresectable or metastatic colorectal cancer. Switching to a different type of anti-VEGF drug in second-line therapy after FOLFOXIRI plus bevacizumab appears to be an attractive treatment strategy when considering survival benefit. It is expected that this phase II study will prove the efficacy of this strategy and that a biomarker for drug selection will be discovered. Trial registration Japan Registry of Clinical Trials jRCTs071190003. Registered April 18, 2019.


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