Risk Factors For Gastrointestinal Toxicity Research Articles

1991: Real world risk factors for gastrointestinal toxicity following radical prostate cancer EBRT

1991: Real world risk factors for gastrointestinal toxicity following radical prostate cancer EBRT

Gastrointestinal Toxicity of High-Dose Melphalan in Autologous Stem-Cell Transplantation: Identification of Risk Factors and a Benchmark for Experimental Therapies

Gastrointestinal (GI) adverse effects are the dose limiting toxicity of high-dose melphalan (HDM), and despite prophylactic measures, continue to have a significant impact on morbidity, length of stay, and quality of life. There are limited contemporary data on gastrointestinal toxicity associated with HDM. Our objective was to characterize the GI toxicity of HDM and identify risk factors for severe toxicity in a cohort of patients.We conducted a retrospective study on 100 consecutive patients with multiple myeloma, amyloidosis, or lymphoma who underwent autologous stem-cell transplant at Columbia University Irving Medical Center using HDM, either alone or in combination with other chemotherapeutic agents. Gastrointestinal adverse events, use of rescue medications, infectious complications, and length of stay were collected from electronic medical records. CTCAE (Common Terminology for Adverse Events) grading for GI events was conducted daily. Risk factors for GI toxicity were identified using linear regression and then examined in a multivariable model.Patients (median age 56 years, range 20-73) had myeloma (42%), lymphoma (42%), or amyloidosis (16%). Melphalan dose was 200 (40%), 140 (59%), or 100 mg/m2 (1%). Ninety-seven percent of patients experienced diarrhea ranging 1 - 18 daily bowel movements (Figure 1) and lasting 0 - 17 days (median 7). Nausea and vomiting of any grade occurred in 88% and 61% of patients, respectively. Sixty-two percent developed grade≥2 diarrhea, and grade≥2 nausea and vomiting was observed in 35% and 7%, respectively. The mean total number of bowel movements during a 14-day period post-transplant was 39 (maximum 67). Rescue loperamide was given 10 doses on average overall (range 0-43). Eighteen percent experienced weight loss of more than 10% and 38% dropped albumin level by at least 1g/dL.Patients with grade≥2 diarrhea had a higher incidence of hypokalemia, hypoalbuminemia, required greater electrolyte repletions (Figure 2), utilized more rescue medications, and had prolonged diarrhea (average 8.7 v. 5 days, p<0.0001) compared to patients with grade 1 diarrhea. Patients with grade≥2 diarrhea were also more likely to stay in the hospital more than 23 days (p=0.07). Of the entire cohort, eleven percent had at least one episode of incontinence and 15% had an infection identified in stool studies. To rule out further complications, 31% of patients had CT scans of the abdomen and pelvis but only 8% showed evidence of colitis.Grade≥2 diarrhea was independently associated with age>50 years (p=0.04), creatinine clearance <60 ml/min (p=0.05), and female sex (p=0.04). Female sex was also associated with developing grade≥1 nausea (p=0.05) and vomiting (p=0.09). Melphalan dose, underlying disease, and HDM v. BEAM (BCNU, Etoposide, Ara-C, Melphalan) were not significantly associated with diarrhea severity, although numerically there were more patients with grade≥2 diarrhea in the HDM 200 mg/m2 compared to 140 mg/m2 (70% vs. 59%).Diarrhea remains a very common side effect of HDM with no improvement over historical rates and no known prophylactic measures. Female sex, a low creatinine clearance, and age over 50 years portend a higher risk for severe diarrhea, and female sex for nausea and vomiting. Novel therapies for chemotherapy-induced diarrhea are critically needed for patients undergoing stem-cell transplantation. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Analysis of Gastrointestinal Toxicity in Patients Receiving Proton Beam Therapy for Prostate Cancer: A Single-Institution Experience

PurposeWe characterized both physician- and patient-reported rates of gastrointestinal (GI) toxicity in patients treated with proton beam therapy (PBT) at our institution for prostate adenocarcinoma and identified factors associated with toxicity. Methods and materialsWe treated 192 patients with PBT between July 2013 and July 2016. Included patients had ≥1 year of follow-up. Potential preexisting clinical and treatment-related risk factors for GI toxicity were recorded. Common Terminology Criteria for Adverse Events version 4.0 was used to score toxicity. Expanded Prostate Cancer Index Composite (EPIC) bowel domain questionnaires assessed patient-reported quality of life. Associations between grade (GR) 2+ toxicity and clinical, treatment, and dosimetric factors were assessed using Cox models and corresponding hazard ratios. ResultsThe median follow-up was 1.7 years. Most of the observed GI toxicity (>90%) was in the form of rectal bleeding (RB). GR2+ GI toxicity and RB actuarial rates specifically at 2 years were 21.3% and 20.4%, respectively. GR3 toxicity was rare, with only 1 observed RB event. No GR4/5 toxicity was seen. The EPIC bowel domain median score was 96 (range, 61-100) pretreatment, 93 (range, 41-100) at 1 year, 89 (range, 57-100) at 1.5 years, and 89 (range, 50-100) at 2 years. Anticoagulation use was the only factor selected during multivariate analysis for predicting GR2+ RB, with a resulting concordance index of 0.59 (95% confidence interval, 0.48-0.68; P = .088). Type of proton technology (pencil beam scanning vs uniform scanning) and number of fields treated per day (1 vs 2) showed no significant difference in toxicity rate. ConclusionsPBT was associated with acceptable rates of GR2+ transient GI toxicity, mostly in the form of RB, which correlated with anticoagulation use. High EPIC bowel domain quality of life was maintained in the 2 years after treatment.

Peptic ulcer disease and non-steroidal anti-inflammatory drugs.

Find out the top 5 risk factors for gastrointestinal toxicity with NSAIDs and how to minimise these adverse effects.

Factors associated with the initiation of proton pump inhibitors in corticosteroid users

Proton pump inhibitors (PPIs) and corticosteroids are commonly prescribed drugs; however, each has been associated with fracture and community-acquired pneumonia. How physicians select patients for co-therapy may have implications for potential additive or synergistic toxicities. We conducted a retrospective cohort study of 13 749 incident corticosteroid users with no prior PPI exposure using the HealthCore Integrated Research Database(SM) . We used logistic regression to evaluate the association between PPI initiation in the first 30 days of steroid therapy and corticosteroid dose, clinical risk factors including comorbid diseases, and medication use including prescription nonsteroidal anti-inflammatory drugs (NSAIDs). A new PPI prescription within 30 days of starting corticosteroids was filled by 1050 patients (7.6%). PPI use was associated with the number of baseline comorbid conditions (OR = 1.21 for each additional condition, 95%CI = 1.13-1.28), recent hospitalization (OR = 4.71, 95%CI = 4.02-5.52), prednisone dose higher than 40 mg/day (OR = 1.87, 95%CI = 1.45-2.41), history of gastroesophageal reflux or gastric ulcer disease (OR = 1.54, 95%CI = 1.24-1.91), renal insufficiency (OR = 2.06, 95%CI = 1.73-2.46), and liver disease (OR = 1.82, 95%CI = 1.45-2.28). The concomitant use of prescription NSAIDs was also associated with PPI use (OR = 1.89, 95%CI = 1.32-2.70); however, the total use of PPIs in this group was low (6.3%, 95%CI = 4.4-8.2%). Overall, PPI therapy among corticosteroid users was uncommon, even among those with risk factors for gastrointestinal toxicity. PPI use was significantly more common among patients who had recently been hospitalized, had a greater burden of comorbid illness, or were receiving high daily doses of corticosteroids.

Dose–Volume Analysis of Predictors for Gastrointestinal Toxicity After Concurrent Full-Dose Gemcitabine and Radiotherapy for Locally Advanced Pancreatic Adenocarcinoma

To identify dosimetric predictors for the development of gastrointestinal (GI) toxicity in patients with locally advanced pancreatic adenocarcinoma (LAPC) treated with concurrent full-dose gemcitabine and radiotherapy (GemRT). From June 2002 to June 2009, 46 LAPC patients treated with definitive GemRT were retrospectively analyzed. The stomach and duodenum were retrospectively contoured separately to determine their dose-volume histogram (DVH) parameters. GI toxicity was defined as Grade 3 or higher GI toxicity. The follow-up time was calculated from the start of RT to the date of death or last contact. Univariate analysis (UVA) and multivariate analysis (MVA) using Kaplan-Meier and Cox regression models were performed to identify risk factors associated with GI toxicity. The receiver operating characteristic curve and the area under the receiver operating characteristic curve (AUC) were used to determine the best DVH parameter to predict for GI toxicity. Of the patients, 28 (61%) received concurrent gemcitabine alone, and 18 (39%) had concurrent gemcitabine with daily erlotinib. On UVA, only the V(20Gy) to V(35Gy) of duodenum were significantly associated with GI toxicity (all p ≤ 0.05). On MVA, the V(25Gy) of duodenum and the use of erlotinib were independent risk factors for GI toxicity (p = 0.006 and 0.02, respectively). For the entire cohort, the V(25Gy) of duodenum is the best predictor for GI toxicity (AUC = 0.717), and the 12-month GI toxicity rate was 8% vs. 48% for V(25Gy) ≤ 45% and V(25Gy) > 45%, respectively (p = 0.03). However, excluding the erlotinib group, the V(35Gy) is the best predictor (AUC = 0.725), and the 12-month GI toxicity rate was 0% vs. 41% for V(35Gy) ≤ 20% and V(35Gy) > 20%, respectively (p = 0.04). DVH parameters of duodenum may predict Grade 3 GI toxicity after GemRT for LAPC. Concurrent use of erlotinib during GemRT may increase GI toxicity.

Strategies to optimize treatment with NSAIDs in patients at risk for gastrointestinal and cardiovascular adverse events

Background: NSAIDs, including cyclooxygenase (COX)-2 inhibitors, are among the most widely prescribed medications worldwide. However, NSAIDs have been associated with gastrointestinal (GI) toxicity. The cardiovascular (CV) toxicity associated with COX-2 inhibitors and some other NSAIDs further complicates the choice of therapy. Objective: The aim of this commentary was to appraise current NSAID treatment strategies and provide clinicians with guidance on the GI and CV risks of these strategies and choosing an appropriate treatment in individual patients. Methods: A literature search of PubMed was conducted (1989-August 2009) to gather relevant studies, meta-analyses, reviews, and treatment guidelines using the following terms, either alone or in combination: NSAID, gastrointestinal, cardiovascular, toxicity, gastroprotection, proton pump inhibitor, COX-2 inhibitor, aspirin, fixed-dose combination, and adherence. Results: Based on the data from the literature search, gastroprotective strategies (eg, proton pump inhibitors [PPIs]) are underused in patients at risk for NSAIDrelated GI complications, including in those patients most at risk. Risk factors for GI toxicity with NSAID use include high NSAID dose, a history of NSAID-associated GI adverse events or the presence of upper GI symptoms, advanced age, corticosteroid use, concurrent aspirin use, and certain comorbidities (eg, rheumatoid arthritis). Risk factors for CV toxicity with NSAID use include established CV disease or an estimated 10-year CV risk >20%. Findings from randomized controlled trials have suggested that, in patients with an increased risk for GI complications, the use of a nonselective NSAID with a PPI may be at least as effective as the use of a COX-2 selective inhibitor in preventing the recurrence of ulcer complications. In patients with a high GI risk and a moderate CV risk, the use of a COX-2 inhibitor with a PPI may be appropriate. Conclusions: The choice of NSAID should be tailored to the GI and CV risks in the patient. The risk profile can be affected by numerous factors, including NSAID dosing and concurrent aspirin use. Thus, individualized risk stratification should be the clinician's primary consideration when selecting treatment.

Inadequate Use of Preventive Strategies in Patients Receiving NSAIDs

Little is known about the factors that influence the decision to use NSAIDs in combination with gastroprotective drugs. The aims of this observational study were to evaluate the extent to which NSAID users are prescribed concomitant gastroprotective drug regimens ('preventive strategies'), and to determine how patient risk factors for NSAID-associated gastrointestinal toxicity and physician prescribing preferences influenced the decision to prescribe a gastroprotective drug in combination with an NSAID. The study was conducted on 29 June 2004 and comprised 109 eligible adult patients hospitalised at the Clinical Hospital Center, Zagreb. Use of NSAIDs and gastroprotective drugs, risk factors for NSAID-associated gastrointestinal toxicity, and physician prescribing preferences were monitored throughout the study. Sixty-six percent of patients receiving proton pump inhibitors or histamine H(2)-receptor antagonists with NSAIDs had no risk factors for gastrointestinal toxicity. Furthermore, 29% of patients who used NSAIDs had risk factors for gastrointestinal toxicity but were not receiving gastroprotective drugs. Even though patients at risk of NSAID-associated gastrointestinal complications had higher odds of receiving preventive strategies (odds ratio 1.25), the absolute rate of utilisation of these therapies in at-risk populations was unacceptably low (69%). However, the strongest independent correlation for gastroprotective drug use was the prescribing physician, with an odds ratio of 6.40. This study demonstrates that an individual physician's prescribing style largely determines the odds of receiving preventive strategies with NSAID treatment and is more important than the patient's risk factors for gastrointestinal toxicity.

Determinants of selective cyclooxygenase-2 inhibitor prescribing: are patient or physician characteristics more important?

Background Little is known about which factors influence the widespread use of selective cyclooxygenase (COX)-2 inhibitors. We examined the relative effects of patient risk factors for gastrointestinal toxicity, other patient characteristics, and physician prescribing preferences on the decision to prescribe a selective COX-2 inhibitor. Methods We retrospectively studied a cohort of 28,190 Medicare beneficiaries who were continuously enrolled in a large, state-run pharmacy benefits program that reimbursed for selective COX-2 inhibitors and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) without restrictions. Half of the study sample filled a prescription for a selective COX-2 inhibitor and the other half for a nonselective NSAID. Multivariable logistic regression models were developed to predict COX-2 inhibitor use. Results Seventeen percent of patients using a COX-2 inhibitor had no identifiable risk factor for NSAID-associated gastrointestinal toxicity, compared with 23% of those using a nonselective NSAID. Established risk factors (age ≥75 years, history of gastrointestinal hemorrhage or peptic ulcer disease, or concomitant warfarin or oral glucocorticoid use) were all significant predictors of COX-2 inhibitor use, but a multivariable model including only these risk factors discriminated poorly between the two patient groups (C statistic = 0.55). Adding other patient clinical and demographic characteristics to the model somewhat improved this association (C statistic = 0.66); however, when physician prescribing preference was included, the model had excellent ability to discriminate between the two treatment groups (C statistic = 0.83). Conclusion Established risk factors for NSAID-associated gastrointestinal toxicity were poor predictors of who was prescribed a selective COX-2 inhibitor; in contrast, physician prescribing preference was an important determinant.

Channelling of controlled release formulation of ketoprofen (Oscorel) in patients with history of gastrointestinal problems.

The aim was to determine if a new controlled release formulation (Oscorel) of the non-steroidal anti-inflammatory drug (NSAID) ketoprofen has been preferentially prescribed in patients with prior history of gastro-intestinal disturbances. The study was a pharmacy records based comparison of the rates of prior prescribing of drugs indicated for peptic ulcer treatment in first recipients of Oscorel in 1989 versus recipients of other NSAID products. A representative panel of Dutch community pharmacies serving approximately 425,000 people was used. Oscorel was launched in January 1989. Data on prescriptions dispensed in 1987-1988 to a total of 837 first users of Oscorel were analysed and compared with the dispensing history of a reference population including 30,787 patients who did not receive a prescription for Oscorel during 1989. Compared to the reference population, first users of Oscorel included a greater proportion of females, of patients 75 years and older, of heavy users of NSAIDs, and of patients switching among different NSAIDs. A total of 24.1% of first users of Oscorel had received peptic ulcer therapy in 1987-1988, versus 15.7% of the reference population. The rate ratio was 1.54, with 95% confidence interval of 1.36-1.74. Adjustment for stratifying variables caused only minor changes in the rate ratio, which remained stable on 1.5. Oscorel appears to have been channelled into use in patients with recognised risk factors for gastrointestinal toxicity. This preferential prescribing probably resulted from expectations and claims that this product has a lower risk of such toxicity.