Common Terminology Criteria For Adverse Events Version Research Articles

Investigating the efficacy and safety of olanzapine prophylaxis for opioid-induced nausea and vomiting (JORTC-PAL20): a study protocol for an open-label, single-arm exploratory study

IntroductionIn opioid therapy for cancer pain, opioid-induced nausea and vomiting (OINV) occur in 20%–40% of patients during initial opioid treatment or increasing opioid doses. OINV result in failure to achieve...

A randomized trial to evaluate the preventive effect of lafutidine on chemotherapy-induced peripheral neuropathy in patients treated with carboplatin and paclitaxel for lung cancer.

Chemotherapy-induced peripheral neuropathy (CIPN) has a significant impact on the therapeutic efficacy of chemotherapy and patients' quality of life. The aim of this study was to assess the preventive effect of lafutidine on CIPN. Patients were randomly assigned (1:1) to carboplatin and paclitaxel chemotherapy with lafutidine 10 mg twice daily (lafutidine group) or without lafutidine (control group). Peripheral neuropathy in both groups was assessed with the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and two patient-based questionnaires, the Patient Neurotoxicity Questionnaire (PNQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx). The primary outcome was the incidence of grade 2 or higher peripheral neuropathy in CTCAE version 5.0. The target number of cases was set at approximately 40. In total, 18 patients were screened, and 16 patients were assigned to the lafutidine group (n=9) or control group (n=7) between January 2021 and January 2023. Due to poor recruitment, the target number of cases was not reached. Grade 2 or higher neuralgia was 22.2% in the lafutidine group and 14.3% in the control group. Grade 2 or higher peripheral sensory neuropathy was 100% in the lafutidine group and 71.4% in the control group (P=0.175). Grade 3 or higher peripheral neuropathy was not detected in either group. There was no significant difference in PNQ scores between the two groups. Median FACT/GOGNtx scores after the fourth cycle tended to be lower in the lafutidine group than in the control group. There was no statistically significant difference in progression free survival (PFS) between the two groups. There were no adverse events due to lafutidine administration. Although the preventive effect of lafutidine on CIPN could not be demonstrated statistically, lafutidine FACT/GOG-Ntx scores showed a trend toward decreased neurotoxicity as chemotherapy proceeded. More reliable studies using lafutidine on the prevention of CIPN should be conducted. Japan Registry of Clinical Trials identifier: jRCTs021200031.

Quality of Life, Efficacy, and Safety of Sequential Intravesical Gemcitabine + Docetaxel versus BCG for Non-Muscle Invasive Urinary Bladder Cancer: A Pilot Study

Purpose: Bacille Calmette-Guerin (BCG) is considered the most effective agent for non-muscle invasive bladder cancer (NMIBC). However, due to BCG-related toxicity, multiple studies have suggested the role of newer chemotherapeutic drugs. The aim of our study was to evaluate intravesical gemcitabine + docetaxel (Gem/Doce) versus BCG with respect to quality of life (QOL), safety, and efficacy in NMIBC. Methods: A total of 60 patients with NMIBC were evaluated between July 2019 and December 2020 in a prospective manner. The sample size calculation was done, keeping in mind the incidence of intravesical BCG-related complications of up to 50–60% and 20–30% for Gem/Doce combination. The p value of 0.05 was kept as statistically significant. The enrollment ratio was kept at 1, and power of study was aimed at 80%. The study population was alternatively assigned to two groups (BCG vs. Gem/Doce) of 30 patients each. Both the groups received 6 weekly doses of induction therapy followed by 6 monthly doses of maintenance therapy if no recurrence was noted at interim follow-up. QOL scores, safety, and efficacy were assessed at beginning of intravesical therapy, end of induction, and 6 months of maintenance therapy. Cystoscopy examination and cytology were performed at the end of induction therapy and 3-monthly thereafter. Result: The preliminary results at the end of 6 months following maintenance therapy showed that the demographic profile, histological stage, and grade were comparable between two groups. The QOL scores using QLQ-30 and QLQ-BLS-24 showed statistically significant differences with the Gem/Doce arm showing better outcomes. There were no progressions to higher stage, while one recurrence each was seen in both groups. Patient-related side effects measured by CTCAE (Common Terminology Criteria for Adverse Events)version 5 showed that the BCG group had higher toxicity profile as compared to Gem/Doce group. Conclusion: Gem/Doce combination intravesical therapy is a promising alternative to BCG for treatment of NMIBC, showing better QOL measures and lesser side effects.

Safety and Effectiveness of Perospirone in Comparison to Risperidone for Treatment of Delirium in Patients with Advanced Cancer: A Multicenter Prospective Observational Study in Real-World Psycho-Oncology Settings.

The clinical benefit of perospirone for treatment of delirium in patients with advanced cancer is not sufficiently clear. The objective of this study was to compare the safety and effectiveness of perospirone to those of risperidone for the treatment of delirium in patients with advanced cancer. This is a secondary analysis of a multicenter prospective observational study in nine psycho-oncology consultation services in Japan. The study used the Delirium Rating Scale (DRS) Revised-98 to measure effectiveness and the CTCAE (Common Terminology Criteria for Adverse Events) version 4 to assess safety. Data from 16 patients who received perospirone and 53 patients who received risperidone were analyzed. The mean age was 70 years in the perospirone group and 73 years in the risperidone group. Both groups showed a significant decrease in the total score of DRS-R-98 after three days of treatment (perospirone: 11.7 (7.9-15.4) to 7.0 (3.3-10.7), difference -4.7, effect size=0.72, p=0.003; risperidone: 15.5 (13.6-17.4) to 12.2 (10.1-14.2), difference -3.3, effect size=0.55, p=0.00). The risperidone group showed significant improvements in sleep-wake cycle disturbance, orientation, attention, and visuospatial ability. In the perospirone group, there was a significant improvement of sleep-wake cycle disturbance. The median daily dose of perospirone was 4 mg/day. There were fewer episodes of somnolence as an adverse event in the perospirone group. Low-dose perospirone was thus found to be effective for the treatment of delirium in patients with advanced cancer and may be associated with fewer episodes of over-sedation as an adverse event.

Docetaxel monotherapy induces necrotic acute pancreatitis

Drug-induced acute pancreatitis (AP) is uncommon and represents 0.1 to 2% of all AP cases. Chemotherapy-induced AP is very rare. Docetaxel monotherapy-induced AP has been reported only once in the literature. Herein we report the second case of docetaxel-related AP and the first case of necrotic AP induced by this agent. We describe the case of a severe docetaxel-induced AP classified as stage E Balthazar in a 55-year-old female treated with adjuvant docetaxel for localized breast cancer. Symptoms occurred five hours following the first infusion of docetaxel. The patient was hospitalized for 15 days for appropriate management. According to the CTCAE (Common Terminology Criteria for Adverse Events) version 5.0 this was a grade 4 toxicity and chemotherapy was withdrawn thereafter. Drug rechallenge was not possible because of the severity of the presentation. Medical oncologists should be aware that docetaxel may induce severe pancreatitis. Therefore, they should prompt testing of serum lipase when patients consult for unusual abdominal pain following chemotherapy infusion. Recognizing this entity is paramount to allow early and appropriate management.

Intensive Immunosupressive Therapy Combining with Eltrombopag for Adult Chinese Patients with Severe Aplastic Anemia

In sight of different pharmacokinetics between races, the recommended dose is 75mg/d for Asian using eltrombopag [1]. However, the efficacy and safety of antithymocyte immunoglobulin (ATG) and cyclosporin A (CsA) with eltrombopag are still largely unknown for adult Asian patients with severe aplastic anemia (SAA).From May 2014 to March 2021, 121 Chinese adult patients with SAA were treated with IST (r-ATG, 3.5mg/kg/d × 5d and CsA 3-5 mg/kg/d) or in conjunction with eltrombopag (75mg/d, from day 1 to 6 months) prospectively and non-randomly. The adverse events (≥3 grades) referring to Common Terminology Criteria for Adverse Events version (CTCAE) 5.0 within 6 months.In pretreatment evaluation of clinical and laboratory characteristics. Median age (39 years and 40 years) was comparable. The complete blood count with differential and quantification of CD4/CD8 T-cell subsets were similar in both groups, but median time from diagnosis to treatment (16 d and 28 d, P=0.038) was different significantly (Table 1).The Chi-Squared test was used to compare the efficacy. The overall response rates (ORR) of IST alone or in combination with eltrombopag in the 1st, 3rd, 6th and 12th month after IST were 12% vs 35% (P=0.002), 44% vs 64% (P=0.028), 61% vs 85% (P=0.006) and 73% vs 91% (P=0.031), respectively. The complete response (CR) rates in the 3rd, 6th and 12th month after IST are 7% vs 17% (P=0.069), 14% vs 27% (P=0.11) and 33% vs 32% (P=0.92) (Table 2).We analyzed factors associated with the efficacy at 6 months by the Binary-Logistic regression model. Elements would be listed in multivariate analysis whether the factors might impact on the efficacy or had P value lower than 0.2 in univariate analysis. It was suggested that ORR was significantly related with the use of eltrombopag (P=0.011, OR=3.600, 95%CI 1.345-9.638) (Table 3).The overall survival (OS) and factors related to survival were analyzed by Kaplan-Meier method and Cox regression model. The OS in IST combined with eltrombopag group was 98% compared to 88% for IST alone (P=0.078). No significant intergroup differences were noted in multivariate analysis of OS.The nonhematologic adverse events (≥3 grades) were infrequent, occurring in 16% patients. 8 in IST plus E-PAG cohort and 11 in IST alone cohort (15% vs 16%, P=0.80). Hepatic injury was prevalent complication (6% vs 8%, P=0.96), relatively. But none showed significant difference between two groups.DiscussionIt has been reported that eltropopag promoted the response of megakaryocytic or even three lineages in refractory SAA [2]. The 6th month CR rate and ORR of our study are lower than the results of Townsley's research with 35% and 94% in the cohort of IST plus eltrombopag [1]. But the CR rate ORR is comparable to De Latour's results with 21.9% and 59.4% in the 3rd month [3]. Median age and dosage of eltrombopag needs to be considered with caution between different researchs, whist the efficacy of horse ATG (hATG) and rATG remained a subject of some debate [4]. Townsley et al. had reported that hepatic impairment (≥3 grades) was 18% [1], but our research showed lower rate of liver impairment with 6%. We should increase the sample volume to analyze the adverse events.Reference[1] Townsley DM, et al. Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia [J]. N Engl J Med, 2017, 376 (16): 1540-1550.[2] Desmond R, et al. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug [J]. Blood, 2014, 123 (12): 1818-1825.[3] De Latour, RP, et al. Results of the EBMT SAAWP Phase III Prospective Randomized Multicenter RACE Study of Horse ATG and Ciclosporin with or without Eltrombopag in naive SAA patients. EBMT 2020 abstract O018.[4] Vallejo, C., et al., Rabbit antithymocyte globulin versus horse antithymocyte globulin for treatment of acquired aplastic anemia: a retrospective analysis. Annals of Hematology, 2015. 94(6): p. 947-954. [Display omitted] DisclosuresHe: F. Hoffmann-La Roche Ltd.: Consultancy; LongBio Pharma: Consultancy, Research Funding.

Ibuprofen gargle for chemo- or Chemoradiotherapy-induced Oral Mucositis: a feasibility study

BackgroundOral mucositis frequently occurs in cancer patients treated with chemotherapy and chemoradiotherapy (CRT). This study examined the safety and efficacy of ibuprofen gargle in healthy volunteers and patients with chemotherapy- and concomitant CRT-induced oral mucositis.MethodsWe enrolled healthy volunteers and patients with chemotherapy- and CRT-induced oral mucositis. In cohort I, single and multiple doses of ibuprofen gargle (0.6% or 1.0%) were administered to healthy volunteers on day 1 and days 4–10. In cohort II, multiple doses of ibuprofen gargle (0.6%) were administered to patients with complicated grade 2–3 oral mucositis based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The primary endpoint of cohort I was the treatment-related adverse events (TRAEs) as defined by CTCAE version 4.0. The primary endpoint of cohort II was the change in the visual analogue scale (VAS) pain score from before to 15 min after gargle use on day 3. The incidence and severity of TRAEs were assessed based on the CTCAE version 4.0 and a subjective rating scale completed by healthy volunteers and patients.ResultsIn cohort I, 9 of 10 healthy volunteers were evaluable for safety. All 9 healthy volunteers reported the TRAE of oral irritation with single or multiple use of the gargle. In cohort II, 10 patients were enrolled and evaluable for safety and 7 of 10 patients were evaluable for efficacy. The mean change in the VAS pain score from before to 15 min after using the gargle on day 3 was − 1.28 (95% confidence interval: − 2.06, − 0.51), and all patients experienced some degree of pain relief (range: − 0.2 to − 2.5). All 10 patients reported the TRAE of oral irritation. No other TRAEs of ibuprofen gargle were observed in the healthy volunteers and patients.ConclusionDespite oral irritation, the ibuprofen gargle appeared to be safe and effective for the pain related to chemo- or CRT-induced oral mucositis. However, ibuprofen-related oral irritation warrants further formulation improvement.Trial registrationThis study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000014433).

Taxane acute pain syndrome (TAPS) in patients receiving chemotherapy for breast or prostate cancer: a prospective multi-center study.

Taxane acute pain syndrome (TAPS) is characterized by myalgias and arthralgias starting 2-3days after taxane-based chemotherapy and lasting up to 7days. In the absence of validated tools, many studies use the presence of both the myalgia and arthralgia components of the Common Terminology Criteria for Adverse Events (CTCAE) to define TAPS. The present study prospectively evaluated the frequency, severity, and impact of TAPS in patients with breast or prostate cancer. In this prospective, non-randomized study, patients with breast or prostate cancer commencing taxane-based chemotherapy completed the CTCAE (version 4.03), the Functional Assessment of Cancer Therapy-Taxane (FACT-T), and Brief Pain Inventory (BPI) questionnaires at baseline and once between days 5 and 7 of each chemotherapy cycle. From March 2015 to April 1, 2016, 75 patients (breast n = 66, prostate n = 9) were enrolled; 83% received docetaxel and 16% paclitaxel and 1% withdrew. After the first cycle of taxane, TAPS was reported by 25/69 (36.2%) patients; a further 8/69 (18.2%) reporting TAPS after a subsequent chemotherapy treatment. Overall incidence of TAPS was 33/75 (44%). While associated with detrimental scores on FACT-T and BPI as well as increased use of analgesics in 63% (21/33) of patients with TAPS, TAPS did not lead to alterations in chemotherapy dosing. TAPS is common after taxane-based chemotherapy, and its presence is associated with reduced quality of life and increased analgesic requirements. Prospective patient-reported outcome assessments are crucial to help individualize treatment strategies and improve management of TAPS.

Comparative Analysis of Efficacy, Toxicity, and Patient-Reported Outcomes in Rectal Cancer Patients Undergoing Preoperative 3D Conformal Radiotherapy or VMAT.

Locally advanced rectal cancer (LARC) patients are usually treated within a multimodal therapy regime, in which the tumor resection plays the major role. This treatment ideally includes 5-fluorouracile (5FU)-based chemoradiation (CRT) leading to significantly improved local control rates. Local therapy as radiotherapy (RT) is required to be adapted referring to side effects and efficacy. Purpose of this study is the comparison of dosimetric parameters, acute and late toxicity, and quality of life in terms of patient-reported outcome (PRO) in patients treated with VMAT or 3D conformal radiotherapy (3DCRT) for LARC. Pelvic RT for LARC was performed with a prescription dose of 45 Gy in 1.8 Gy per fraction, 50.4 Gy in 1.8 Gy per fraction, or 50 Gy in 2 Gy per fraction. Chemotherapy included 5FU or 5FU/Oxaliplatin or Capecitabine-based RT. Acute and late toxicity were evaluated via National Institute Common Terminology Criteria for Adverse Events version (CTCAE) v4.03 and the Scoring System Late effects of Normal Tissue. Quality of life was established via EORTC QLQCR29. After a median follow-up of 38 months (VMAT) and 78 months (3DCRT) there was no significant difference in progression-free survival (p = 0,85) but a significant difference in overall survival (p = 0.032). Regarding dose-volume parameters, patients treated with VMAT plans had a lower V20 of the bladder than 3DCRT-treated patients (p = 0.004). VMAT plans can also reduce Dmean of the right (p = 0.002) and left (p < 0.001) femoral head. Acute side effects between the VMAT and 3DCRT patients showed no significant difference. But concerning long-term effects, VMAT-treated patients had a significant lower appearance of high grade anal incontinence (p = 0.032). Quality of life (PRO) showed no significant different between the patients except of hair loss and worrying about weight. VMAT treatment of LARC in preoperative CRT revealed a reduction of dose to organs at risk (OARs) as bladder and femoral heads. However, no changes in acute and long-term toxicity profiles were detectable. For late toxicity and quality of life data longer follow-up times are required.

Abstract PD4-08: Efficacy of compression therapy using surgical gloves for nanoparticle albumin-bound-paclitaxel-induced peripheral neuropathy: A phase II multicenter study by the Kamigata breast cancer study group

Abstract PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect of many commonly used chemotherapeutic agents, including taxanes. However, there is currently no established effective prophylactic management for CIPN. Thus, we investigated the efficacy of using surgical glove (SG) compression therapy to prevent nanoparticle albumin-bound-paclitaxel (nab-PTX)-induced peripheral neuropathy. PATIENTS AND METHODS: Patients with primary and recurrent breast cancer who received 260 mg/m2 of nab-PTX were eligible for this case-control study. The patients wore two SGs of the same size, that is, one size smaller than the size that fit, on their dominant hand for 90 minutes. They did not wear SGs on the non-dominant hand, which served as the control hand. Peripheral neuropathy was evaluated at each treatment cycle using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and the Patient Neurotoxicity Questionnaire (PNQ). The temperatures of each fingertip of the compression SG-protected and control hands were measured by using thermography. RESULTS: Between August 2013 and January 2016, 43 patients were enrolled, and 42 were evaluated. As shown in Table 1, the overall occurrence of ≥grade 2 sensory and motor peripheral neuropathy according to the CTCAE was significantly lower in the SG-protected hands than in the control hands (76.1% vs. 21.4% and 57.1% vs. 26.2%, respectively, p &amp;lt; 0.0001). The PNQ results showed that the incidence of ≥grade 4 neuropathy was significantly higher in the control hands than in the SG-protected hands in terms of both sensory and motor neurotoxicity (p &amp;lt; 0.0001, Table 2). As the treatment cycles of nab-PTX increased, the mean CTCAE and PNQ grades of the control hands gradually increased. However, the SG-protected hands maintained significantly lower mean grades than the control hands over time (p &amp;lt; 0.0001). No patients withdrew from this study because they could not tolerate the compression from the SGs. The mean temperature of each fingertip significantly decreased (1.42–2.60 °C) in the SG-protected hands compared to in the control hands. CONCLUSIONS: SG compression therapy appears effective for reducing nab-PTX-induced peripheral neuropathy. The nab-PTX exposure to the peripheral nerve may be decreased because the SG decreases microvascular flow to the fingertip. Table 1: Comparison of the overall occurrences of the different grades of peripheral neuropathy according to CTCAE version 4.0 between the compression surgical glove-protected hands and control handsCTCAE v.4.0SensoryMotorGradeSurgical GloveControlSurgical GloveControl012418712161311292411163080840000 Table 2: Changes in the overall occurrence of the Patient Neurotoxicity Questionnaire (PNQ) grade with surgical glove compression therapyPNQSensoryMotorGradeSurgical gloveControlSurgical gloveControl194209223512113717912431611050000 Citation Format: Tsuyuki S, Senda N, Kanng Y, Yamaguchi A, Yoshibayashi H, Kikawa Y, Katakami N, Kato H, Hashimoto T, Okuno T, Yamauchi A, Inamoto T. Efficacy of compression therapy using surgical gloves for nanoparticle albumin-bound-paclitaxel-induced peripheral neuropathy: A phase II multicenter study by the Kamigata breast cancer study group [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD4-08.

Asking the right questions to get the right answers: using cognitive interviews to review the acceptability, comprehension and clinical meaningfulness of patient self-report adverse event items in oncology patients

Background: Standardized reporting of treatment-related adverse events (AE) is essential in clinical trials, usually achieved by using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) reported by clinicians. Patient-reported adverse events (PRAE) may add value to clinician assessments, providing patient perspective on subjective toxicity. We developed an online patient symptom report and self-management system for real-time reporting and managing AE during cancer treatment integrated with electronic patient records (eRAPID). As part of this program we developed a patient version of the CTCAE (version 4.0), rephrasing terminology into a self-report format. We explored patient understanding of these items via cognitive interviews.Material and method: Sixty patients (33 female, 27 male) undergoing treatment were purposively sampled by age, gender and tumor group (median age 61.5, range 35–84, 12 breast, 12 gynecological, 13 colorectal, 12 lung and 11 renal). Twenty-one PRAE items were completed on a touch-screen computer. Subsequent audio-recorded cognitive interviews and thematic analysis explored patients’ comprehension of items via verbal probing techniques during three interview rounds (n = 20 patients/round).Results: In total 33 item amendments were made; 29% related to question comprehension, 68% response option and 3% order effects. These amendments to phrasing and language improved patient understanding but maintained CTCAE grading and key medical information. Changes were endorsed by members of a patient advisory group (N = 11).Conclusion: Item adaptations resulted in a bank of consistently interpreted self-report AE items for use in future research program. In-depth analysis of items through cognitive interviews is an important step towards developing an internationally valid system for PRAE, thus improving patient safety and experiences during cancer treatment.

Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer: A Retrospective, Single-Center Study of 55 Patients

Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) is an effective treatment for patients with early-stage non-small cell lung cancer (NSCLC) who are not surgical candidates or who refuse surgical management. In this study, we report on our clinical outcomes and toxicity in the treatment of early-stage NSCLC with SBRT. Methods and Materials: Fifty-five patients with 59 T1-2N0M0 NSCLC lesions were treated at our institution between December 2009 and August 2014. The majority of the patients [38 (69%)] were treated with 50 Gy in 5 fractions, 7 patients (13%) with 48 Gy in 4 fractions, 8 patients (14%) with 60 Gy in 3 fractions, 1 patient (2%) with 62.5 Gy in 10 fractions, and 1 patient (2%) with 54 Gy in 3 fractions. Tumor response was evaluated using RECIST 1.1, and toxicity was graded using the CTCAE (Common Terminology Criteria for Adverse Events) version 3.0. The primary endpoints of this retrospective review included rates of overall survival, disease-free and progression-free survival, local failure, regional failure, and distant failure. A secondary endpoint included radiation-related toxicities. Results: The median follow-up was 23.8 months (range 1.1-57.6). The 3-year local control, progression-free survival, and overall survival rates were 91, 55, and 71%, respectively. The median age at diagnosis was 67.9 years (range 51.4-87.1). There were a total of 54 T1N0 tumors (92%) and 5 T2N0 lesions (8%). Adenocarcinoma was the most common pathology, comprising 54% of the lesions. A total of 16 of the patients (29%) failed. Among these, 5 local (9%), 14 regional (25%), and 4 distant failures (7%) were observed. On follow-up, one patient had grade 2 and another had grade 5 pneumonitis. Three patients experienced grade 2 chest wall tenderness. Two patients had grade 1 rib fractures, one of which could not be discerned from radiation-induced toxicity versus a traumatic fall. Conclusion: The University of Mississippi Medical Center SBRT experience has shown that SBRT provides satisfactory local control and overall survival rates with minimal toxicity in early-stage NSCLC patients.

Self-evaluation of Adjuvant Chemotherapy-Related Adverse Effects by Patients With Breast Cancer.

Patient perspective on chemotherapy-related adverse effects is being increasingly acknowledged both in experimental clinical trials and in clinical practice. To evaluate a 10-item, paper questionnaire derived from the US National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for patient-reported chemotherapy-related adverse effects. Prospective, single-arm study of 604 women with breast cancer receiving standard adjuvant chemotherapy conducted at 11 outpatient oncology clinics at academic and nonacademic Italian hospitals between January 2011 and October 2013. The CTCAE version 4.0 definitions of grade of severity for nausea, vomiting, constipation, anorexia, dysgeusia, diarrhea, fatigue, pain, paresthesia, and dyspnea were translated into Italian and rephrased. Questionnaires were administered after the first and third cycle of chemotherapy. Adverse effect information was also extracted from the medical records to compare with patient-reported data. Differences in adverse effect-reporting between paired questionnaires and agreement between patient and physician adverse effect-reporting (grade 0 vs grade ≥1) were studied. Linear regression was used to study the effect of the number of patients enrolled at each institution on the magnitude of discrepancy in adverse effect-reporting between patients and physicians. A total of 604 women (median age, 53.4 years; interquartile range, 45.0-62.7 years) were enrolled. The number of patients enrolled at each site varied between 6 and 236. Three patients withdrew consent prior to starting the first cycle of adjuvant chemotherapy. After cycle 1 of adjuvant chemotherapy, 596 patient questionnaires were collected, and 581 patient questionnaires were collected after cycle 3. Of the questionnaires collected, 594 and 573 had corresponding questionnaire results extracted from medical records at the same time point. The median (interquartile range) percentage of completed questionnaire fields was 82% (80%-88%) for both the first and third cycle questionnaires, and the results of the 2 patient questionnaires showed a reduction in vomiting (severity), diarrhea (both incidence and severity), and pain (both incidence and severity), as well as a statistically significant increase in dysgeusia (both incidence and severity) and dyspnea (both incidence and severity) in the second patient-completed questionnaire. The frequency and severity of chemotherapy-related adverse effects were consistently greater in patient-reported data than physician-reported data. As a result, interrater agreement was low for most adverse effects, ranging from 0.10 for anorexia to 0.54 for vomiting (Cohen κ statistic). There was a strong and significant positive correlation between the magnitude of the discrepancy in the frequency of reporting adverse effects and the number of patients enrolled at each site. Adherence to reporting adjuvant chemotherapy-related adverse effects using the CTCAE system is high in women undergoing adjuvant chemotherapy for breast cancer. Workload may contribute to agreement discrepancies by limiting the physician-patient relationship.

Adverse event grading following CTCAE v3.0 underestimates hypertensive side effects in patients with glioma treated with Bevacizumab.

Anti-VEGF therapy with Bevacizumab (BEV) is widely used in cases of relapsed high-grade glioma (HGG). Arterial hypertension is a known side effect of anti-VEGF therapy. 42 Patients with relapsed HGG were treated with BEV 10mg/kg on days 1 and 15 of 28-day cycles in addition to treatment with 40mg TMZ daily until disease progression, based on magnetic resonance imaging and/or worsening of clinical status. In a retrospective analysis, hypertensive side effects were evaluated as the primary endpoint, while survival information in addition to toxicity was analyzed as secondary endpoint. Grading which employs the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 detected hypertensive events with a significantly higher sensitivity than CTCAE version 3.0. The rate of severe hypertensive events observed as CTCAE≥°3 were 9.5% in version 3.0 and 45.2% in version 4.0. The results presented here indicate that CTCAE version 3.0 may underreport the incidence and grade of BEV-induced hypertension within clinical trials. As hypertension has not only long-term, but also severe short-term side effects, we suggest that arterial hypertension under BEV should be scored according to CTCAE version 4.0 to avoid clinically relevant hypertension-related adverse events in these patients.

An adverse event capture and management system for cancer studies.

BackgroundComprehensive capture of Adverse Events (AEs) is crucial for monitoring for side effects of a therapy while assessing efficacy. For cancer studies, the National Cancer Institute has developed the Common Terminology Criteria for Adverse Events (CTCAE) as a required standard for recording attributes and grading AEs. The AE assessments should be part of the Electronic Health Record (EHR) system; yet, due to patient-centric EHR design and implementation, many EHR's don't provide straightforward functions to assess ongoing AEs to indicate a resolution or a grade change for clinical trials.MethodsAt UAMS, we have implemented a standards-based Adverse Event Reporting System (AERS) that is integrated with the Epic EHR and other research systems to track new and existing AEs, including automated lab result grading in a regulatory compliant manner. Within a patient's chart, providers can launch AERS, which opens the patient's ongoing AEs as default and allows providers to assess (resolution/ongoing) existing AEs. In another tab, it allows providers to create a new AE. Also, we have separated symptoms from diagnoses in the CTCAE to minimize inaccurate designation of the clinical observations. Upon completion of assessments, a physician would submit the AEs to the EHR via a Health Level 7 (HL7) message and then to other systems utilizing a Representational State Transfer Web Service.ConclusionsAERS currently supports CTCAE version 3 and 4 with more than 65 cancer studies and 350 patients on those studies. This type of standard integrated into the EHR aids in research and data sharing in a compliant, efficient, and safe manner.

Adverse drug reaction profile of pegylated liposomal doxorubicin versus conventional doxorubicin: An observational study

Background : Potential life-threatening cardiac toxicities limit the lifetime dose of doxorubicin. The pegylation of the molecule protects the drug from detection by methoxypolyethylene glycol resulting increase of circulation time. Encapsulation of doxorubicin inside a pegylated liposome alters bioavailability, biodistribution and thus its biological activity significantly. We conducted an intensive monitoring of the adverse drug reactions (ADRs) profile of pegylated liposomal doxorubicin (PLD) in comparison with conventional doxorubicin in a tertiary care cancer center. Materials and Methods : ADR data were collected from 30 patients receiving PLD and 30 age-matched controls receiving conventional doxorubicin in this longitudinal observational study. Severity was graded as per US National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAEs). For the evaluation of acute and chronic toxicities, we adopted the basic scale from CTCAE version 4 of the National Cancer Institute. Results : The median disease duration was greater in PLD arm. Totally, 357 ADRs were noted with PLD and 375 with conventional doxorubicin. Of these, 75 (21%, 95% confidence interval [CI] 13.69-28.33%) in the PLD group and 60 (16.26%, 95% CI: 9.74-22.78%) in the conventional doxorubicin group were of grade 3/4 severity. Common events included myelosuppression, nausea, vomiting, anorexia, stomatitis, palmer-planter erythrodysesthesia, alopecia with PLD and myelosuppression, nausea, vomiting, anorexia, stomatitis, alopecia, and cardio-toxicities with conventional doxorubicin. For hematological toxicities, there was no statistical significant difference between two arms. Furthermore, gastrointestinal toxicities (nausea, vomiting, diarrhea, anorexia and stomatitis) were same for both arms. Among the skin toxicities palmar-plantar-erythrodysesthesia grade 2 toxicity was found in 60% patients receiving liposomal doxorubicin (P = 0.046). In cardio-toxicities, left ventricular ejection dysfunction found in 60% patients of conventional doxorubicin arm (P - 0.038). Conclusions: This observational study suggests that PLD has a better tolerability with less ventricular dysfunction but increased yet manageable palmar-plantar-erythrodysesthesia. This needs confirmation through further interventional study.

Efficacy and Safety of Percutaneous Cryoablation for Stage 1A/B Renal Cell Carcinoma: Results of a Prospective, Single-Arm, 5-Year Study

Percutaneous cryoablation is gaining in popularity as a viable treatment option for renal cell carcinoma (RCC). We present the 5-year oncologic outcomes of a prospective trial. Over a 5-year period, we treated 134 consecutive patients with biopsy-proven RCC with CT-guided percutaneous cryoablation. All were treated while under conscious sedation. Technical objective was for the ice ball to cover the lesion plus a 5-mm margin. Hydro- or air dissection was utilized to aid in technical success as needed. Efficacy was defined as the lack of enhancement and/or enlargement of a previously enhancing lesion on follow-up imaging. Safety was assessed by the common terminology criteria for adverse events (CTCAE), version 4.0. The 1-, 2-, 3-, 4-, and 5-year efficacy of percutaneous cryoablation for RCC was 99.2, 99.2, 98.9, 98.5, and 97.0%, respectively. Median tumor size was 2.8 ± 1.4 cm. All-cause mortality during the study period was 3 (none from RCC), yielding an overall 5-year survival of 97.8%. The cancer-specific 5-year survival was 100%. No patient developed metastatic disease during the follow-up period. The overall significant CTCAE version 4.0 complication rate was 6%, with the most frequent being transfusion-requiring hemorrhage, at 1.6%. There was one 30-day mortality unrelated to the procedure. CT-guided percutaneous cryoablation for renal cancer offers very high efficacy, approaching that of the gold standard, with a more favorable safety profile.

The Case for Including Bowel Urgency in Toxicity Reporting After Pelvic Cancer Treatment

Bowel toxicity is a major complication of cancer treatment, and its accurate reporting is important for assessing outcomes. The NCI's Common Terminology Criteria for Adverse Events (CTCAE) is the preferred method for capturing adverse events after all cancer treatments, particularly within clinical trials. However, the CTCAE version 4 does not include urgency of defecation as an item, despite this being one of the most common and persistent adverse consequences of treatment of pelvic cancers. The importance of bowel urgency to patients is well documented, and this treatment effect has a negative impact on social function and quality of life. Bowel urgency is also important clinically because it may represent significant underlying problems. This article presents the case for including patient reported assessment of bowel urgency as an independent item in cancer treatment adverse event reporting.

Effect of pretreatment prostate volume on urinary quality of life following intensity-modulated radiation therapy for localized prostate cancer

BackgroundThe aim of this study was to describe the effect of pretreatment prostate volume on urinary quality of life after intensity-modulated radiation therapy (IMRT) for clinically localized prostate cancer.MethodsA total of 368 men treated with prostate IMRT (77.4–81 Gy) were stratified into three gland volume groups, ie, <30 g (group 1), 30–60 g (group 2), and >60 g (group 3). Post-IMRT urinary function was evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 genitourinary guidelines at one year post-IMRT, and surveyed by the International Prostate Symptom Score (IPSS) before treatment, and then at one month and one year post-IMRT.ResultsLate (one year post-IMRT) CTCAE version 4.0 genitourinary toxicity occurred in 11/368 (3.0%) men, but was not severe (grade ≥ 3); total toxicity was similar between the prostate volume groups (P = 0.86). Continuous prostate volume neither correlated with (P = 0.50) nor predicted late genitourinary toxicity (univariate odds ratio 0.99, 95% confidence interval 0.96–1.02). The total IPSS cohort, group 1 (<30 g) and 2 (30–60 g), showed a similar IPSS trend of elevation from pretreatment baseline to one month post-IMRT (each P < 0.01), then a reduction to baseline at one year (each P < 0.01). Group 3 (>60 g) had the highest pretreatment IPSS, but uniquely showed a better urinary symptom trend than the smaller volume groups, with similar IPSS from baseline to one month post-IMRT (P = 0.88) and improved post-treatment IPSS from baseline at one year (P = 0.003).ConclusionPretreatment prostate volume and initial IPSS scores were not associated with increased late genitourinary toxicity after IMRT in our series. Patients with smaller prostates had an initial increase in urinary symptoms, but returned to baseline at one year. Larger prostate glands (>60 g) had comparatively worse pretreatment symptoms, but at one year showed an overall improvement in IPSS versus baseline.

The Efficacy and Toxicity of Bevacizumab in Combination With Gemcitabine in Patients With Recurrent Ovarian Cancer

BackgroundTo evaluate the efficacy and toxicity of bevacizumab in combination with gemcitabine in patients with recurrent ovarian cancer. Patients and MethodsA retrospective analysis identified patients with recurrent ovarian cancer who received combination bevacizumab and gemcitabine. The patients received bevacizumab (15 mg/m2) every 3 weeks, plus gemcitabine (750–1000 mg/m2) on days 1 and 8 until disease progression or undue toxicity. Toxicity was assessed by using National Cancer Institute CTCAE (Common Terminology Criteria for Adverse Events) version. 3.0. Response rates were determined by serial cancer antigen 125 levels and by radiologic evaluation. ResultsTwenty-nine patients were treated with combination therapy. The median age was 51 years (range, 38–70 years); 59% had primary platinum-resistant disease. The median number of previous chemotherapy regimens was 2 (range, 1–5). Five patients experienced grade 3/4 nausea and vomiting. Four patients had grade 3/4 neutropenia. One patient had grade 3/4 proteinuria, and no patients had grade 3/4 hypertension. Eight patients had the bevacizumab infusion delayed due to proteinuria. Six patients had the gemcitabine infusion delayed or reduced due to grade 3/4 toxicity. One patient developed a colovesical fistula. Three patients developed a colon obstruction. Two patients (7%) had a complete response, and 9 patients (31%) had a partial response for an overall response rate of 38%. The median duration of response was 9.6 months (range, 1–49 months). Four patients (14%) had stable disease, and 14 patients (48%) had progressive disease. ConclusionCombination treatment with bevacizumab and gemcitabine has activity in recurrent ovarian cancer and is well tolerated. Prospective trials are needed to further characterize the role of this regimen in the treatment of recurrent ovarian cancer.