scholarly journals FOLFIRI and regorafenib combination therapy with dose escalation of irinotecan as fourth-line treatment for patients with metastatic colon cancer according to UGT1A1 genotyping

2014 ◽  
pp. 2143
Author(s):  
Jaw-Yuan Wang ◽  
Chien-Yu Lu ◽  
Yung-Sung Yeh ◽  
Ching-Wen Huang ◽  
Cheng-Jen Ma ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Combination Therapy ◽  
Dose Escalation ◽  
Metastatic Colon Cancer ◽  
Line Treatment

scholarly journals Ibrutinib-Induced Vasculitis in a Patient with Metastatic Colon Cancer Treated in Combination with Cetuximab

2020 ◽  
Vol 2020 ◽  
pp. 1-4 ◽  
Author(s):  
Jeffrey Chi ◽  
Jennifer Park ◽  
Muhammad Wasif Saif
Keyword(s):  
Colon Cancer ◽  
Growth Factor ◽  
Combination Therapy ◽  
Growth Factor Receptor ◽  
Hematologic Malignancies ◽  
Hair Follicles ◽  
Metastatic Colon Cancer ◽  
Egfr Inhibitor ◽  
Gastrointestinal Malignancies ◽  
Btk Inhibitor

Combination therapy with ibrutinib and cetuximab is being studied in a phase 1b/2 trial in patients with advanced gastrointestinal and genitourinary malignancies. Rash is a common cutaneous adverse effect for both medications. Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor approved for the treatment of several hematologic malignancies. The rash can be asymptomatic, nonpalpable, mild skin eruption, or palpable purpuric rash. A rarer panniculitis form has also been reported. Cetuximab, an epidermal growth factor (EGFR) inhibitor, approved for treatment in head and neck and advanced gastrointestinal malignancies is also known to cause acneiform rash in majority of patients. The rash is due to inhibition of EGFR in the basal keratinocytes and hair follicles. In the case of ibrutinib, the off-target effects on EGFR, c-kit, and platelet-derived growth factor receptor (PDGFR) are thought to be responsible for the cutaneous eruption of various forms of rash. The combination therapy with the BTK inhibitor and a direct EGFR inhibitor may potentiate the rash inducing effects of the drugs. Here, we describe a case of vasculitis in a patient with metastatic colon cancer who received both ibrutinib and cetuximab on a phase Ib/II clinical trial.

scholarly journals Clinical activity of patupilone in patients with pretreated advanced/metastatic colon cancer: results of a phase I dose escalation trial

2011 ◽  
Vol 105 (11) ◽  
pp. 1646-1653 ◽  
Author(s):  
B Melichar ◽  
E Casado ◽  
J Bridgewater ◽  
J Bennouna ◽  
M Campone ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Phase I ◽  
Dose Escalation ◽  
Clinical Activity ◽  
Metastatic Colon Cancer

Survival benefit associated with the number of chemotherapy/biologic treatment lines in 5,129 metastatic colon cancer patients.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 559-559 ◽  
Author(s):  
Nader Hanna ◽  
Corinne Woods ◽  
Zhiyuan Zheng ◽  
Ebere Onukwugha ◽  
Brian S. Seal ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Metastatic Colon Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Biologic Treatment ◽  
Mortality Hazard ◽  
Line Therapy ◽  
Hazard Ratios ◽  
First Line Treatment

559 Background: The purpose of this study was to investigate the association between multiple chemotherapy/biologic treatment lines and survival among patients diagnosed with metastatic colon cancer (mCC). Methods: Patients aged 66 to 105 years old diagnosed with mCC between 2003 and 2007 were selected for analysis from the Surveillance, Epidemiology and End Results SEER-Medicare data to determine the association between chemotherapy/biologic treatment lines and survival. We examined the survival benefits using Cox proportional-hazards regressions with inverse probability weighting method to adjust for the probability of receiving treatment lines. Results: Patients with no chemotherapy/biologic treatment had an adjusted median survival time of 6.8 months. Each chemotherapy/biologic treatment line received was associated with longer adjusted median survival times: 11.9 months, 23.2 months and 26.4 months for receipt of first-line treatment only, second-line treatment and subsequent treatment, respectively. Colon cancer-specific mortality hazard ratios (HRs) were 0.637, 0.391 and 0.350 (p<0.001 for each) for first-line, second-line and subsequent treatments, respectively. Overall mortality hazard ratios were 0.604, 0.398 and 0.364 (p<0.001 for each) for first-line, second-line and subsequent treatments, respectively. Compared to receiving only first-line treatment, proceeding to second-line treatment was associated with longer colon cancer-specific survival (HR=0.614, p<0.001) and longer overall survival (HR=0.659, p<0.001). Patients with a low-graded tumor had longer colon cancer-specific and overall survival (HR=0.746, p<0.001; HR=0.762, p<0.001, respectively) and lived 5.6 months longer. Factors associated with shorter survival were a higher age category and being female. Conclusions: Among mCC patients who survived at least 3 months from diagnosis, each chemotherapy/biologic treatment line was independently associated with significantly longer survival. Proceeding from first-line to second-line therapy or having a low-graded tumor was also associated with longer survival. Proceeding from second-line third-line therapy showed neither benefit nor harm.

scholarly journals Efficacy of continuing anti-angiogenic agents in the second-line treatment for metastatic colon cancer depending on the KRAS mutation status: a meta-analysis

2018 ◽  
Vol 8 (2) ◽  
pp. 38-45
Author(s):  
M. Yu. Fedyanin ◽  
A. A. Tryakin ◽  
S. A. Tjulandin
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Metastatic Colon Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Kras Gene ◽  
Mutation Status ◽  
Free Survival

Objective: to assess the efficacy of anti-angiogenic agents incorporated into second-line chemotherapeutic regimens for metastatic colon cancer depending on the KRAS gene mutation status.Materials and methods. We selected completed prospective randomized controlled phase III clinical trials evaluating the efficacy of antiangiogenic agents (bevacizumab, ramucirumab and aflibercept) added to second-line chemotherapy for metastatic colon cancer with subanalysis of treatment efficacy depending on the KRAS gene mutation status. Meta-analysis was performed using the ReviewManager (RevMan) v. 5.3 (The Cochrane Collaboration, Denmark).Results. Three studies (ML18147, RAISE, VELOUR) involving 2165 patients (1137 with KRAS wild-type tumors and 1028 with KRAS-mutant tumors) met the inclusion criteria and were included into this meta-analysis. The majority of patients (84 %) received bevacizumab in the first-line treatment. The results of our meta-analysis suggest that adding an anti-angiogenic drug to chemotherapy in patients with KRAS wildtype colon cancer significantly improved both progression-free survival (hazard ratio (HR) 0.71; 95 % confidence interval (CI) 0.62–0.80; р<0.00001; I2 = 22 %, p = 0.21) and overall survival (HR 0.76; 95 % CI 0.66–0.88; р= 0.0001; I2 = 0, p = 0.59). In patients with KRASmutant colon cancer, incorporation of an anti-angiogenic drug into the treatment regimen was not associated with better overall survival (ОР0.9; 95 % CI 0.79–1.03; р= 0.11; I2 = 0, p = 0.98), although improved progression-free survival (HR 0.78; 95 % CI 0.68–0.89; р= 0.0002; I2 = 0, p = 0.46). Conclusion. Continuation of anti-angiogenic therapy in the second-line treatment for metastatic colon cancer is most effective in patients with KRAS wild-type tumors. In individuals with KRAS-mutant tumors, continuation of bevacizumab or switch to another anti-angiogenic agent in the second-line treatment improves progression-free survival and has a statistically insignificant effect on overall survival.

Use of biologics in addition to chemotherapy in the treatment of elderly Medicare patients with stage IV metastatic colon cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14602-e14602
Author(s):  
C. Daniel Mullins ◽  
Fenghao Wang ◽  
Kaloyan A. Bikov ◽  
Brian S. Seal ◽  
Nader Hanna
Keyword(s):  
Colon Cancer ◽  
Small Sample Size ◽  
Stage Iv ◽  
Small Sample ◽  
Metastatic Colon Cancer ◽  
Line Treatment ◽  
First Line ◽  
Biologic Drugs ◽  
Nccn Guidelines ◽  
First Line Treatment

e14602 Background: On February 12 and 26, 2004, the FDA approved bevacizumab and cetuximab, respectively, two biologic drugs for the first–line treatment of metastatic colorectal cancer (mCC), followed by panitumumab, another biologic approved on September 27, 2006. NCCN guidelines suggest that biologics may be added to fluorouracil and leucovorin (5-FU/LV), irinotecan (IRI), or oxaliplatin (OX), yet a number of recent articles raise questions regarding the added benefit of biologics on top of a backbone chemotherapy regimen, which might affect the utilization pattern of biologics. To examine the adoption of biologics, we document the rate of treatment with biologics in addition to backbone chemotherapy as first-line treatment (Tx1) of mCC. Methods: This study uses the Surveillance, Epidemiology and End Results (SEER)-Medicare data and examines mCC patients diagnosed in 2003-2007 who received chemotherapy with or without biologics as Tx1. Due to the small sample size of cases involving the combined use of irinotecan and oxaliplatin (IROX) as Tx1, IROX patients were excluded from this study. The remaining 2995 observations are broken down by regimen and by year of Tx1 initiation (Table). Results: The use of biologics (90% of which was bevacizumab) in addition to chemotherapy as part of Tx1 exploded from 9% in 2004 to 55% in 2005. Utilization was highest (62%) in 2006 and fell slightly in 2007 to 57%. Of all cases utilizing biologics, 67% were oxaliplatin-based regimens, 19% were fluorouracil-based regimens and 15% were irinotecan-based regimens. Conclusions: In the first few years following FDA approval, the use of biologics in addition to backbone chemotherapy increased rapidly as first-line treatment of elderly Medicare metastatic colon cancer patients, leveling out at around half of all patients receiving chemotherapy. Biologics use has been most common among patients treated with oxaliplatin. [Table: see text]

How do first-line treatment and other factors affect the receipt of second-line treatment for elderly metastatic colon cancer patients?

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 592-592
Author(s):  
Zhiyuan Zheng ◽  
Ebere Onukwugha ◽  
Nader Hanna ◽  
Emily S Reese ◽  
Brian S. Seal ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cox Regression ◽  
Age Groups ◽  
Median Income ◽  
Metastatic Colon Cancer ◽  
Line Treatment ◽  
Hospital Bed ◽  
Wheel Chair ◽  
Zip Code ◽  
Significant Factors

592 Background: Metastatic colon cancer (mCC) patients might receive multiple lines of chemotherapy to improve survival or quality of life. However, factors associated with receipt of 1st and 2nd line treatment (TX) haven’t been fully investigated. Methods: Elderly (65+) SEER-Medicare patients diagnosed with mCC in 2003-2007 were followed until death or 12/31/2009 to examine factors for receipt of 1st and 2nd line TX. A Cox regression framework and inverse probability weighting (IPW) method were used to adjust for patients’ informative (death) and non-informative (dropout or end-of-study) censoring histories. Additionally, we controlled for patients’ 1st line TX in the IPW to determine factors for receipt of 2nd line TX. Results: Of 7,951 mCC patients, 3,266 patients received at least 1 line TX, and 1,440 went on to 2nd line TX. For 1st line TX, significant clinical factors were CCI = 2 (HR = 0.86; p = 0.02), oxygen use (HR = 0.74; p = 0.04), walking aid use (HR = 0.58; p = 0.02), and wheel chair use (HR = 0.50; p < 0.01); significant demographic characteristics were age groups 95+ (HR = 0.11; p < 0.01), 85-94 (HR = 0.24; p < 0.01), 75-84 (HR = 0.70; p < 0.01), as compared to 65+-74, female (HR = 1.12; p < 0.01), married (HR = 1.43; p < 0.01), and African American (AA) (HR = 0.80; p < 0.01); significant factors for socio-economics status were state buy-in status (SBI) (HR = 0.97; p < 0.01), and zip code level household median income (HR = 1.03; p < 0.01). For 2nd line TX, significant factors were hospital bed use (HR = 2.82; p = 0.05), oxygen use (HR = 0.68; p = 0.02), age group 85-94 (HR = 0.718; p = 0.02) as compared to 65+-74, and days delayed for 1stline TX (HR = 0.998; p < 0.01). Conclusions: Various factors were associated with receipt of 1st line TX. Conditional on the receipt of 1st line TX, many factors became insignificant for receipt of 2nd line TX, such as age, female, marriage status, AA, SBI, and zip code level household income. Hospital bed use reduced the probability of receipt of 1st line TX, but increased the probability of receipt of 2nd line TX.

Does first-line treatment impact the cost-effectiveness of second-line treatment for elderly metastatic colon cancer patients?

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 585-585
Author(s):  
C. Daniel Mullins ◽  
Andinet Woldemichael ◽  
Zhiyuan Zheng ◽  
Ebere Onukwugha ◽  
Brian S. Seal ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cost Effectiveness ◽  
Real World ◽  
Survival Benefit ◽  
Metastatic Colon Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
The Real ◽  
First Line Treatment

585 Background: Randomized clinical trials for second line treatment (Tx2) of metastatic colon cancer (mCC) often have strict inclusion/exclusion criteria regarding prior treatment, yet in the real world there is significant variation. This study aims to determine whether cost effectiveness estimates of Tx2 for elderly mCC patients varies by the regimen they received in first-line treatment (Tx1). Methods: We identified 3,211 elderly (age 66+) mCC patients in the SEER-Medicare dataset who received NCCN recommended Tx1 between 2003 and 2009. Patients were categorized by Tx1 based on a previously published algorithm as fluorouracil and leucovorin (5-FU/LV), irinotecan (IRI), oxaliplatin (OX), or “other,” which included IROX or biologics without OX or IRI. Separate 5-year incremental cost-effectiveness of Tx2 were calculated for each Tx1. Approximately 1% of patients with outlier costs were excluded. Patients enrolled in HMOs, lost Part A and/or B, and died of causes other than colon cancer are censored. We adjusted for censoring using the Inverse Probability Weighting (IPW) method. Costs were inflation-adjusted to 2009 dollars using the national monthly medical price index. Results: Among patients who received Tx1, 34% (n=1,090) received 5FU, 17% (n=530) received IRI, 46% (n=1,481) received OX, and 3% (n=110) received other (IROX or Biologics) regimens; 44.5% (n=1,440) proceeded to Tx2. Compared to those who do not receive Tx2, patients who received Tx2 following IROX or Biologics, IRI and 5FU in Tx1 live 292 (se = 4), 224 (se = 2), and 191 (se = 2) days longer and incur added costs of $49,096 (se = $7,137), $83,784 (se = $12,322), and $91,686 (se = $10,312), respectively. Recipients of OX in Tx1 did not receive a survival benefit from Tx2, despite additional costs of $46,849 (se = $10,468). Conclusions: The real-world survival benefit of Tx2 for elderly mCC patients in SEER-Medicare varied based on Tx1 from potential harm to a mean of 292 days of incremental survival. Similarly, the costs and cost effectiveness of Tx2 varied by Tx1. These results underscore the importance of considering prior treatment when evaluating the benefit of subsequent treatment for elderly mCC patients.

The impact of comorbidity on costs and effects of second-line treatment among elderly metastatic colon cancer patients.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 536-536
Author(s):  
Andinet Woldemichael ◽  
Ebere Onukwugha ◽  
Zhiyuan Zheng ◽  
Nader Hanna ◽  
Brian S. Seal ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cost Effectiveness ◽  
Incremental Cost ◽  
Cancer Patients ◽  
Metastatic Colon Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Elderly Age ◽  
Co Morbidity ◽  
The Impact

536 Background: The Charleston Co-morbidity Index (CCI) was developed as in hospital mortality indicatory and subsequently has been used to both predict and adjust survival differences in cancer patients. We therefore sought to examine how the incremental cost effectiveness of treating elderly metastatic colon cancer (mCC) patients with second-line treatment (Tx2) will vary based upon their baseline CCI. Methods: We identified 2,897 elderly (age 66+) mCC patients who received NCCN recommended first-line treatment (Tx1) between 2003 and 2009 in the SEER-Medicare dataset. Approximately 6% and 1% of patients with missing CCI and outlier costs, respectively, were excluded. We categorized patients by their CCI for 12 months prior to diagnosis into three categories: low (CCI = 0), medium (CCI = 1) and high (CCI = 2+). We calculated 5-years cost-effectiveness of Tx2. Patients enrolled in HMOs, lost part A and/or B, and died of causes other than colon cancer are censored. Costs are inflation adjusted to January 2009 dollars using U.S. Medical Price Index (MPI). We adjusted for censoring using Inverse Probability Weighting (IPW) method and selection bias on observables using Propensity Score Bin Bootstrapping method. Results: Among patients who received Tx1, 56% (n = 1,285) proceeded to receive Tx2. Of those who received Tx2, 67% (n = 864), 23% (n = 289), and 10% (n = 132) have low, medium and high comorbidities, respectively. Compared to those who do not received Tx2, patients who received Tx2 with low, medium, and high baseline comorbidities live 18 (se = 4), 253 (se = 4), and 183 (se = 3) days longer and incur added costs of $66,693 (se = $675), $80,217 (se = $723), and $49,610 (se = $1,136), respectively. The median Incremental Cost-Effectiveness Ratios (ICERs) of Tx2 for patients with low, medium, and high comorbidity are $80,049, $114,693, and $151,627, respectively. Conclusions: Survival benefits from receiving Tx2 vary from an average of 18 days to 253 days and added costs from $49,610 to $80,217 depending on baseline comorbidity levels. The median ICERs associated with Tx2 increase as baseline comorbidity level of patients increase.

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