Chemotherapy-related Adverse Events Research Articles

Profiles of Symptom Suffering and Functioning in Children and Adolescents Receiving Chemotherapy.

Some children and adolescents receiving chemotherapy experience few symptom-related adverse events, whereas others experience multiple adverse events. If oncology nurses could identify patients likely to have pronounced chemotherapy-related adverse events, tailored supportive care could be matched to these patients' symptom burdens. The aim of this study was to identify symptom profiles in children and adolescents before and after chemotherapy, and the sociodemographic and psychological factors associated with profile classification and change. Participants ranging from 7 to 18 years (n = 436) completed 6 Patient-Reported Outcomes Measurement Information System pediatric symptom measures within 72 hours preceding (T1) and 1 to 2 weeks after (T2) chemotherapy. Profile membership and change were determined by latent profile/latent transition analyses. Associations with profiles and profile transitions were examined using multinomial logit models and logistic regression. Three symptom suffering profiles were identified at T1 and T2: high, medium, and low. The high symptom suffering profile included the fewest participants (T1, n = 70; T2, n = 55); the low symptom suffering profile included the most participants (T1, n = 200; T2, n = 207). Of the participants, 57% remained in the same profile from T1 to T2. Psychological stress was significantly associated with T1 and T2 profile classifications and profile transition; age was associated with profile classification at T1. Three symptom suffering profiles existed in a sample of pediatric patients undergoing chemotherapy, indicating that children and adolescents have differing cancer treatment experiences. Oncology nurses could screen pediatric oncology patients for their symptom suffering profile membership and subsequently prioritize care efforts for those with a high suffering profile.

OP09 Association of patient sex with chemotherapy-related adverse events: A multicenter retrospective cohort study

OP09 Association of patient sex with chemotherapy-related adverse events: A multicenter retrospective cohort study

Implementation of a proactive outreach program to patients with gastrointestinal malignancies starting new chemotherapy regimens.

340 Background: Gastrointestinal oncology patients (GIOP) at Fox Chase Cancer Center (FCCC) disproportionately require emergency department (ED) or urgent care (UC) evaluation due to chemotherapy-related adverse events (CRAE). Between January 2014 - June 2018, GIOP comprised 24% of visits to the FCCC ED and 29% of visits to the FCCC UC center, though specific patient and disease characteristics are unavailable. Prior to March 2022 there was no process to proactively contact patients to assess for CRAE or provide symptom management education (SME) following the administration of a new intravenous chemotherapy (IVC). This contributed to a perception of higher volumes of patient-initiated phone calls for acute CRAE management, SME, and UC/ED evaluations as compared to other disease sites, leading to patient and provider dissatisfaction. Methods: We aimed to contact at least 50% of all GIOP starting new IVC through a standardized nurse-initiated phone call within 72 hours of a patient’s first infusion by June 2022. A multidisciplinary team of medical oncology fellows, nurses, and clinic managers launched this initiative through participation in the ASCO Quality Training Program. A series of Plan-Do-Study-Act (PDSA) cycles were conducted over 12 weeks. All GIOP starting a new IVC were electronically identified on a weekly basis by the infusion room scheduling system. Clinic nurses called patients from this list to assess symptoms, provide SME, and advise early intervention for CRAE. A smart phrase was developed for efficient yet comprehensive documentation in the electronic medical record (EMR). EMR documentation was reviewed weekly to determine if calls were made within 72 hours of treatment, which guided subsequent PDSA cycles. Results: From March 14, 2022 to June 3, 2022, a list of all GIOP starting a new IVC was generated and consistently distributed weekly to nurses embedded in 6 GI oncology clinics. Over 12 weeks, 40 (56%) of 71 patients receiving a new IVC were called and 37 (52%) of the patients were called within 72 hours. Of the patients who were called, 93% were called within the intended time frame. Nurses documented their outreach calls in the EMR utilizing a standardized smart phrase to summarize CRAE assessments and SME. Acute or unresolved issues were triaged to the patient’s primary oncology team for further guidance. Conclusions: This initiative successfully introduced a nursing-led outreach phone call to GIOP starting a new IVC, though additional PDSA cycles are needed to achieve more consistent outreach. We plan to standardize outreach to patients with organized SME while striving to automate performance monitoring. Further evaluation of this intervention, which will eventually better identify patients at highest risk for acute unplanned care needs, will assess the impact of patient-reported outcomes and health care utilization.

Survival Analysis and Clinical Outcomes between Paclitaxel and Carboplatin Versus Carboplatin and Gemcitabine in Patients with Advanced-stage Non-small-cell Lung Cancer: A Single-center Cohort Study.

Palliative chemotherapy using platinum-based doublet chemotherapy was recommended as one of the standard treatments in patients with advanced-stage non-small cell lung cancer (NSCLC) with negative EGFR mutation. This study aimed to compare clinical outcomes between patients treated with paclitaxel and carboplatin (PC) and those treated with carboplatin and gemcitabine (CG). We conducted a retrospective cohort study comparing PC and CG at Hatyai Hospital between 2012 and 2019. The primary outcome was survival analysis, and the secondary outcome was chemotherapy-related adverse events, and the rate and reason for stopping chemotherapy. The median overall survivals of both groups was comparable (9.0 months for the PC group and 9.6 months for the CG group; log-rank, p=0.287). The CG group had a higher incidence of adverse events (89.7% vs. 77.9%, p=0.010) and tended to have a lower rate of chemotherapy discontinuation (29.6% vs. 41.2%, p=0.080) than the PC group. In the multivariate analysis, female sex (odds ratio [OR]=0.351; 95% confidence interval [CI], 0.158-0.780; p=0.010) and higher performance status (OR=76.374; 95%CI, 32.533-179.295; p<0.001) were independent predictive factors for stopping chemotherapy. In the proportional hazards model, the factors associated with decreased survival included higher performance status (hazard ratio [HR]=1.939; 95%CI, 1.388-2.709; P<0.001) and discontinuation of chemotherapy (HR=2.572; 95%CI, 1.792-3.691; p=<0.001). These two platinum-based regimens had comparable effects on overall survival. The CG group had a higher incidence of chemotherapy-related adverse events, while the PC group had a marginally significantly higher rate of stopping chemotherapy from unacceptable adverse events and deterioration of patients' clinical status.

1154P Geriatrics predictors of 3-months overall survival and chemotherapy toxicities in older patients with metastatic non-small cell lung cancer

Geriatric assessment (GA) has been advocated for treatment decision in the elderly population which is at high risk of over and under-treatment. However, tumor-specific data are still missing. Our study investigated geriatric predictors of overall survival (OS) and severe chemotherapy related adverse events (CRAEs) in elderly patients treated for metastatic non-small cell lung cancer (mNSCLC) and deemed eligible for chemotherapy. We conducted a secondary analysis from ESOGIA phase III trial, which randomized patients with mNSCLC, >70 years, into 2 arms treated either according to an algorithm based on GA or according to a standard evaluation. The present analysis is based on the entire population, who all received a GA, without corrective actions. Main endpoint was 3-months OS, secondary endpoint was CRAEs grade 3 or more of the CTCAE v4.0 classification. Multivariate Cox and logistic models adjusted for time-varying chemotherapy cycle, centers and stratified by randomization arms, were performed. A total of 493 subjects were included: median age was 77 years, 74.2% were male, 79.6% were former or current smoker, 18.9% had performance status (PS) = 2, 23.9% had comorbidities with Charlson comorbidity index ≥ 2. Three months OS rate was 29.4% [CI 95% 25.2%-34.1%]. The main predictors of 3-months mortality were male gender, altered PS, loss of Instrumental Activities of Daily Living (IADL), altered mobility (Test Get Up and Go), weight loss, anemia, increased CRP/Albumine ratio and LDH. Recent weight loss interacted negatively with IADL score ≤ 6 for 3-months mortality (HR=5.71, CI95% 2.64–12.32). Comorbidities were independently related to more severe CRAEs (OR=1.94 CI 95% 1.06 – 3.56). In an elderly mNSCLC patients, deemed eligible for chemotherapy, autonomy, mobility and weight loss and combination were independent geriatric factors of early death, while comorbidities were independently associated with CRAES.

Efficacy of Lentinula edodes Mycelia Extract on Chemotherapy-Related Tasted Disorders in Pancreatic Cancer Patients

Patients undergoing chemotherapy suffer from taste disorders that affect the quality of life (QOL). In this study, a randomized, double-blind, placebo-controlled trial was conducted to explore the effectiveness of AHCC®, a standardized extract of cultured Lentinula edodes mycelia, for chemotherapy-related adverse events and taste disorders in patients with gastrointestinal cancer. Patients who received chemotherapy were randomized to receive either placebo or AHCC®. The study endpoints were the incidence of anemia and taste disorders assessed with changes in nutritional parameters. Ninety-eight patients with pancreatic ductal adenocarcinoma (PDAC) were enrolled in this study, with 55 patients randomly assigned to the AHCC® group and 43 to the placebo group. The incidence of grades 2-3 anemia in the AHCC® group who were receiving chemotherapy was not significantly different compared to that of the placebo group (Risk difference; −3.1% [95% confidence intervals (CI): −22.8% to 16.9%], p = 0.8392). In the AHCC® group, the occurrence of taste disorders during chemotherapy was significantly lower, and the nutritional parameters were significantly improved compared to those in the placebo group (Risk difference; 28.6% [95% CI: 7.5% to 47.8%], p = 0.0077). AHCC® appears to prevent taste disorders in patients with advanced PDAC who were receiving chemotherapy. AHCC® is expected to enable patients who need chemotherapy to improve nutritional status and their QOL.

Guideline discordant care in patients with metastatic germ cell tumors.

Despite high curability, patients with metastatic germ cell tumors (GCT) in the United States general population persistently face inferior outcomes compared with those treated in specialty referral centers. We characterized guideline discordant management in patients with metastatic GCT who experienced relapse after first-line chemotherapy and compared those who were initially treated in community practices vs. academic referral centers. Retrospective analysis of 53 patients with relapsed GCT between 2005 and 2018. First-line GCT management was assessed against the National Comprehensive Cancer Network guidelines. Guideline discordant management, predictors of discordance, and associations with outcomes were assessed. Of 53 patients with relapsed GCT, 34% received guideline discordant care in the first-line setting. Guideline discordant care was more prevalent in patients initially treated in community practices (12/30, 40%) vs. those initially treated in academic centers (3/22, 14%), though in multivariate logistic regression, this difference was not statistically significant (odds ratio: 4.07, P = 0.08). Most patients in community settings who received guideline discordant care were undertreated (10/12, 83%). There were 3 major reasons for guideline discordant care: (1) failure to resect residual masses after chemotherapy (27%, 4/15), (2) mismanagement of chemotherapy-related adverse events (27%, 4/15), and (3) under staging at diagnosis, resulting either insufficient chemotherapy regimen intensity (13%, 2/15) and/or inappropriately receiving primary surgical resection for metastatic disease (20%, 3/15). Under treatment was identified in nearly half of patients initially treated in a community setting who later developed relapsed GCT. Referral to specialized centers for a second opinion should be considered for all metastatic GCT patients in the first-line setting and all patients with post-chemotherapy residual disease. More effective methods should be developed to facilitate second opinions from expert centers in the United States.

Early onset metastatic colorectal cancer in patients receiving panitumumab-based upfront strategy: Overall and sex-specific outcomes in the Valentino trial.

Anti-EGFRs plus doublet chemotherapy is considered the optimal upfront option for RAS/BRAF wild-type left-sided metastatic colorectal cancer (mCRC). Early-onset (EO) mCRC has an increasing incidence and its prognostic/predictive role and management is debatable. We performed a post hoc analysis of Valentino study, that randomized RAS wild-type mCRC patients to two panitumumab-based maintenance regimens after FOLFOX/panitumumab induction. We assessed the safety and efficacy outcomes in patients stratified for age (<50/≥50 years old). We assessed progression-free survival (PFS), overall survival (OS), response rate (ORR), rate of treatment-related and panitumumab-related adverse events (AEs) and quality of life (QoL). In 229 patients enrolled, 35 (15%) had EO mCRC, with a higher rate of female sex (P= .020) and lower rate of primary tumor resection (P= .001). Median PFS and OS were 10.9 vs 10.8months (P= .593) and 28.1 vs 27.5months (P= .865) in patients <50 and ≥50 years old, respectively, with no significant impact of maintenance arm. ORR and disease control rate were 74% vs 65% (P= .337) and 97% vs 81% (P= .013) in patients <50 or ≥50 years old. In younger patients, a trend for increased chemotherapy-related AEs (peculiarly anemia) was shown, while significantly decreased EGFR-related hypomagnesemia and increased skin rash were reported. No significant differences in treatment intensity or QoL were observed. In patients with EO mCRC and RAS wild-type status, we found no differences in terms of survival outcomes based on age when selecting maintenance strategies. Management of treatment-related AEs should consider the differential toxicity profile of age and sex.

GSTP1 c.313A > G mutation is an independent risk factor for neutropenia hematotoxicity induced by anthracycline-/paclitaxel-based chemotherapy in breast cancer patients

BackgroundThe link between glutathione S-transferase P1 (GSTP1) c.313A > G polymorphism and chemotherapy-related adverse events remains controversial. The goal of this study was to assess how this variant affected the toxicity of anthracycline-/paclitaxel-based chemotherapy in patients with breast cancer.MethodsThis study retrospectively investigated pharmacogenetic associations of GSTP1 c.313A > G with chemotherapy-related adverse events in 142 breast cancer patients who received anthracycline and/or paclitaxel chemotherapy.ResultsThere were 61 (43.0%), 81 (57.0%), 43 (30.3%), and 99 (69.7%) patients in the T0-T2, T3-T4, N0-N1, and N2-N3 stages, respectively. There were 108 (76.1%) patients in clinical stages I–III and 34 (23.9%) patients in clinical stage IV. The numbers of patients with luminal A, luminal B, HER2 + , and triple-negative breast cancer (TNBC) were 10 (7.0%), 77 (54.2%), 33 (23.2%), and 22 (15.5%), respectively. The numbers of patients who carried GSTP1 c.313A > G A/A, A/G, and G/G genotypes were 94 (66.2%), 45 (31.7%), and 3 (2.1%), respectively. There were no statistically significant differences in the proportion of certain toxicities in patients with A/G, G/G, and A/G + G/G genotypes, except for neutropenia, in which the proportion of patients with A/G + G/G (χ2 = 6.586, P = 0.035) genotypes was significantly higher than that with the AA genotype. The logistic regression analysis indicated that GSTP1 c.313A > G mutation (A/G + G/G vs. A/A genotype) (adjusted OR 4.273, 95% CI 1.141–16.000, P = 0.031) was an independent variable associated with neutropenia.ConclusionsThe findings of this study indicate that the GSTP1 c.313A > G mutation is an independent risk factor for neutropenia hematotoxicity in breast cancer patients induced by anthracycline-/paclitaxel-based chemotherapy.

Real-world outcomes of Black women versus non-Hispanic White women with advanced triple-negative breast cancer treated with immune checkpoint inhibitors at an urban cancer center.

1074 Background: Black women (BW) are disproportionately diagnosed with metastatic triple negative breast cancer (mTNBC) compared to Non-Hispanic White women (NHW). Median overall survival (OS) in mTNBC remains poor at 12-18 months. While immune checkpoint inhibitors (ICIs) are a promising treatment strategy, BW were significantly underrepresented in pivotal clinical trials that led to the approval of ICIs in mTNBC. Therefore, the efficacy, safety, and optimal biomarkers of ICI response in BW remain unknown. We sought to compare baseline characteristics and outcomes between BW and NHW with mTNBC treated with an ICI and chemotherapy at an urban tertiary care institution. Methods: BW and NHW with advanced unresectable or mTNBC treated with an ICI plus chemotherapy at Emory University between 2019 and 2021 were retrospectively evaluated. Baseline characteristics, including next generation sequencing (NGS), as well as clinical outcomes between BW and NHW were compared using Kruskal-Wallis tests and Fisher’s exact tests. Progression free survival (PFS) and OS were analyzed with the Kaplan-Meir method. Results: Forty-one women with PDL-1 positive mTNBC treated with an ICI and chemotherapy were identified [BW, n = 26 (63%) and NHW, n = 15 (37%)]. A majority of patients had relapsed disease (73%); however BW were more likely to have de novo metastatic disease compared to NHW (38% vs 7%, p = 0.03). Twenty-seven (66%) patients received atezolizumab and 14 (34%) were treated with pembrolizumab. Of the 23 (56%) patients with NGS testing, alterations in TP53, PIK3CA, and BRCA were seen in 23 (100%), 5 (31%), and 1 (6%) patient, respectively. Median tumor mutational burden was similar between BW and NHW (5 vs 7, p = 0.8). BW had numerically lower median PDL-1 (SP142) compared to NHW (1% vs 2%, p = 0.5). Rates of immune and dose-limiting chemotherapy-related adverse events were similar between BW and NHW (Table). There were no differences in ICI response between groups, though BW had fewer complete responses and a shorter median PFS compared to NHW. Median OS was 12 months in BW compared to 28 months in NHW (p = 0.1). Conclusions: Our experience with real-world use of this regimen showed that BW had fewer complete responses and a trend towards worse OS compared to NHW. BW had numerically lower median PDL-1 expression compared to NHW, suggesting further investigation of biomarkers, potentially by Race, are needed to better identify responders to ICI in mTNBC. [Table: see text]

The quality of life in neoadjuvant versus adjuvant therapy of esophageal cancer treatment trial (QUINTETT): Randomized parallel clinical superiority trial.

BackgroundWe compared the health‐related quality of life (HRQOL) in patients undergoing trimodality therapy for resectable stage I‐III esophageal cancer.MethodsA total of 96 patients were randomized to standard neoadjuvant cisplatin and 5‐fluorouracil chemotherapy plus radiotherapy (neoadjuvant) followed by surgical resection or adjuvant cisplatin, 5‐fluorouracil, and epirubicin chemotherapy with concurrent extended volume radiotherapy (adjuvant) following surgical resection.ResultsThere was no significant difference in the functional assessment of cancer therapy‐esophageal (FACT‐E) total scores between arms at 1 year (p = 0.759) with 36% versus 41% (neoadjuvant vs. adjuvant), respectively, showing an increase of ≥15 points compared to pre‐treatment (p = 0.638). The HRQOL was significantly inferior at 2 months in the neoadjuvant arm for FACT‐E, European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ‐OG25), and EuroQol 5‐D‐3 L in the dysphagia, reflux, pain, taste, and coughing domains (p < 0.05). Half of patients were able to complete the prescribed neoadjuvant arm chemotherapy without modification compared to only 14% in the adjuvant arm (p < 0.001). Chemotherapy related adverse events of grade ≥2 occurred significantly more frequently in the neoadjuvant arm (100% vs. 69%, p < 0.001). Surgery related adverse events of grade ≥2 were similar in both arms (72% vs. 86%, p = 0.107). There were no 30‐day mortalities and 2% vs. 10% 90‐day mortalities (p = 0.204). There were no significant differences in either overall survival (OS) (5‐year: 35% vs. 32%, p = 0.409) or disease‐free survival (DFS) (5‐year: 31% vs. 30%, p = 0.710).ConclusionTrimodality therapy is challenging for patients with resectable esophageal cancer regardless of whether it is given before or after surgery. Newer and less toxic protocols are needed.

Adjuvant Chemotherapy in Node-Negative Advanced Gastric Cancer Patients.

Currently, there is still controversy on postoperative adjuvant chemotherapy for node-negative advanced gastric cancer. Herein, we sought to evaluate the role of postoperative adjuvant chemotherapy in these patients. We retrospectively analyzed the clinical and pathological characteristics of 363 node-negative advanced gastric cancer patients in our hospital from 1996 to 2007 who underwent gastrectomy and D2 lymphadenectomy. We compared the survival rate of the surgery-only group with that of the adjuvant chemotherapy treatment group. The 5-year survival rates of patients in the surgery-only group and the chemotherapy treatment group were 70.7% and 73.8%, respectively. There was no significant difference in the survival rate between patients receiving postoperative chemotherapy and patients not receiving chemotherapy (P=0.328). However, postoperative chemotherapy treatment significantly increased the survival rate of pT4aN0M0 patients (P=0.020), although it did not exert a direct effect on the survival rate in pT2N0M0 and pT3N0M0 patients (P=0.990 and P=0.895). We also summarized and analyzed the side effects and safety of postoperative adjuvant chemotherapy. The rate of chemotherapy-related adverse events was 79.9%. Although 61 (36.1%) patients had to adjust their chemotherapy dose, no patient died from side effects. In conclusion, postoperative chemotherapy treatment is safe but did not show a direct impact on the survival rate of the node-negative advanced gastric cancer patients. However, pT4aN0M0 patients can benefit from postoperative adjuvant chemotherapy after undergoing D2 radical resections.

Proton Pump Inhibitors Enhance the Antitumor Effect of Chemotherapy for Esophageal Squamous Cell Carcinoma.

Simple SummaryThe use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in some cancers. This study aimed to evaluate the effect of PPIs on 5-Fuorouracil (5-FU)-based therapy for advanced esophageal cancer based on in vitro experiments and a clinical study. In the present study, PPIs showed a dose-dependent antitumor effect on esophageal cancer cells and enhanced the sensitivity of esophageal cancer cells to 5-FU at sublethal concentrations. In the clinical setting, patients treated with oral PPIs showed a superior tumor response to 5-FU and better overall survival in comparison to the non-PPI group. These results indicate that PPIs can enhance chemosensitivity in esophageal cancer patients treated with 5-FU.Background: Vacuolar ATPase (V-ATPase) is involved in cancer development. The use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in certain cancers. This study aimed to evaluate the effect of PPIs on chemotherapy for esophageal cancer. Methods: To investigate the effects of PPIs on esophageal cancer cells, human KYSE50 and 70 cells were plated and 3 PPIs (lansoprazole, esomeprazole, vonoprazan) were added at various concentrations with 5-Fluorouracil (5-FU) to the corresponding cells for a cell viability assay. To investigate the effects of PPI treatment on patients undergoing 5-FU-based therapy in the clinical setting, we retrospectively analyzed the clinical outcomes and chemotherapy-related adverse events in 40 esophageal cancer patients who received 5-FU chemotherapy in our hospital between May 2013 and April 2017. Results: In the viability assays, all PPIs significantly enhanced the cytotoxic effect of 5-FU on the two esophageal cancer cell lines. In the clinical study, PPI-treated patients showed better overall survival (OS) than patients managed without PPI treatment. A multivariate analysis revealed that PPI treatment was independently associated with OS (p = 0.009, HR, 0.33; 95% CI, 0.12–0.76). Conclusions: PPI treatment may safely enhance chemosensitivity in esophageal cancer patients.

Validity of the Cancer and Aging Research Group Predictive Tool in Older Japanese Patients.

Simple SummaryThis study aimed to assess the usefulness of the Cancer and Aging Research Group (CARG) predictive tool in predicting chemotherapy-related adverse events (CRAEs) in elderly Japanese patients with cancer. The CARG has developed a very useful tool that can predict CRAEs among patients with solid tumors aged above 65 years. However, considering that this tool is based on data from Europe and the United States, the usefulness of the tool for Japanese people, who have different sensitivities to anticancer drugs and varying life expectancies, is still unknown. This study showed that the CARG tool could help predict CRAEs in elderly Japanese patients with cancer, i.e., this tool has the potential to optimize chemotherapy in elderly Japanese patients with cancer.Background: This study aimed to evaluate the usefulness of the Cancer and Aging Research Group (CARG) predictive tool in older Japanese patients with cancer. Methods: Patients aged 65 years or older with solid tumors treated with new anticancer regimens in Kakogawa Central City Hospital between April 2016 and March 2019 were included. Grade 3 or higher risks of developing chemotherapy-related adverse events (CRAEs) were calculated using the tool (low-, intermediate-, or high-risk scores). The association between grade 3–5 CRAE incidence during the first course of each regimen and the calculated risk or the patient characteristics was evaluated. The difference in the incidences of CRAEs between the groups was evaluated by Fisher’s exact test. Results: This study examined 76 patients (mean age: 71 (65–82) years). The incidence of grade 3–5 CRAE was 38%, 55%, and 76% in patients classified as low, medium, and high CARG risk scores (p = 0.035), and the incidence of severe non-hematological toxicities was 4%, 31%, and 52% (p < 0.01), respectively. Eastern Cooperative Oncology Group performance status and age were not associated with chemotherapy toxicity. Conclusions: The CARG predictive tool was valid, suggesting its usefulness in optimizing chemotherapy outcomes in older patients with cancer.

Real-world safety and supportive care use of second-line 5-fluorouracil-based regimens among patients with metastatic pancreatic ductal adenocarcinoma

Objective Chemotherapy-related adverse events (AEs) can negatively impact the care of patients. The prevention and management of AEs often require additional medications. This study evaluated the percentages of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) undergoing second-line therapy with 5-fluorouracil (5-FU)-based regimens that experienced AEs during treatment and received medication to manage those AEs. Methods We conducted a retrospective observational analysis utilizing the Flatiron Health database of adult patients with mPDAC who started second-line therapy between January 2016 and August 2020. The occurrence of diarrhea, fatigue, nausea and vomiting, neuropathy, and hematologic AEs including G3/G4 anemia, neutropenia, and thrombocytopenia was assessed. The use of concomitant medications including atropine and granulocyte colony stimulating factor (G-CSF) was assessed. Results Of the 825 eligible patients, 29.0% (n = 239) received FOLFIRINOX, 24.0% (n = 198) received FOLFOX, 6.8% (n = 56) received FOLFIRI, and 40.2% (n = 332) received liposomal irinotecan-based regimens. FOLFIRI and FOLFIRINOX regimens were associated with the highest rates of anemia (16.1% and 15.5%), neutropenia (19.6% and 22.6%), and thrombocytopenia (14.3% and 9.6%). The liposomal irinotecan and FOLFOX regimens were associated with lower rates of anemia (11.8% and 12.1%), neutropenia (12.4% and 14.7%), and thrombocytopenia (2.4% and 8.1%). G-CSF use was observed among 63.6%, 34.9%, 33.9%, and 44.9% of patients treated with FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan-based regimens, respectively. Diarrhea was observed among 12.5%, 4.5%, 12.5%, and 10.2% of patients who were treated with FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan-based regimens, respectively. Nausea and vomiting occurred in 14.9%, 12.6%, 10.5%, and 13.1% of patients treated with FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan-based regimens, respectively. Atropine use was higher in patients treated with FOLFIRINOX and FOLFIRI (90.8% and 94.6%, respectively) than in patients treated with liposomal irinotecan-based regimens (75.6%). Conclusions In patients with mPDAC who received second-line therapy, those who received liposomal irinotecan-based regimens had the lowest rates of anemia, neutropenia, and thrombocytopenia compared to FOLFIRI, FOLFIRINOX, and FOLFOX, while requiring a similar or lower level of medication to treat and manage those adverse events. Patients treated with FOLFIRI received the highest dose of pegfilgrastim to manage neutropenia. The results of this real-world analysis are consistent with prior evaluations of patients with mPDAC and highlight the importance of managing adverse events and associated cost implications.

FOLFOXIRI and bevacizumab in patients with early-onset metastatic colorectal cancer. A pooled analysis of TRIBE and TRIBE2 studies

BackgroundWe performed a pooled analysis of TRIBE and TRIBE2 studies to assess the efficacy and safety of the intensification of upfront chemotherapy backbone – from doublets to the triplet FOLFOXIRI – in combination with bevacizumab (bev) in patients with early-onset metastatic colorectal cancer (EO-mCRC; aged <50 years) and to explore whether EO-mCRCs have a peculiar tumour genomic profiling. Materials and methodsSubgroup analyses according to age (<50 versus ≥50 years) and treatment (FOLFOXIRI/bev versus doublets/bev) were carried out for rates of any grade and grade ≥3 (≥G3) overall and singular adverse events, progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Tumour genomic profiling was obtained using a DNA-based next-generation sequencing platform. ResultsOf 1187 patients included, 194 (16%) patients were aged <50 years. Females were more frequently diagnosed with EO-mCRC (P = 0.04). Patients aged <50 years showed a lower risk of ≥G3 neutropenia (P = 0.07), diarrhoea (P = 0.04), asthenia (P = 0.008) and a higher risk of any grade nausea (P < 0.01) and vomiting (P < 0.01). Patients receiving FOLFOXIRI/bev more frequently experienced ≥G3 chemotherapy-related adverse events respect to doublets/bev, regardless of age (Pinteraction = 0.60). FOLFOXIRI/bev was associated to a lower incidence of neutropenia (P = 0.04) and asthenia (P = 0.01) in patients <50 years old, than those aged ≥50 years. PFS, OS and ORR did not differ according to age (PFS P = 0.81, OS P = 0.44, ORR P = 0.50) and no interaction between age and the benefit from the intensification of upfront chemotherapy was observed (PFS Pinteraction = 0.72, OS Pinteraction = 0.54, ORR Pinteraction = 0.65). Genomic profiling was assessed in 296 patients, showing an enrichment of FBXW7 and POLE mutations in EO-mCRC. ConclusionsUpfront FOLFOXIRI/bev shows a favourable efficacy/safety balance in EO-mCRC. Trial registrationClinicaltrials.gov Identifiers NCT00719797, NCT0233-9116.

Predicting Chemotherapy-Related Adverse Events in Elderly Cancer Patients with Prior Anticancer Therapy.

To test the usefulness of the Cancer and Aging Research Group (CARG) predictive tool, it was used to assess elderly cancer patients with prior anticancer therapy. Among patients with solid malignancies aged ≥ 65 years receiving second-line chemotherapy who were admitted to the Department of Medical Oncology/Hematology at Kakogawa Central City Hospital between April 2016 and September 2019, the risk ≥ grade 3 of developing chemotherapy-related adverse events (CRAEs) (low, intermediate, or high) was calculated using the tool. Correlations between grades 3 and 5 CRAE incidence rates in the first course of each regimen and CARG risk score, age, and Eastern Cooperative Oncology Group performance status (ECOG PS) were assessed. Included patients (n = 62) had a mean age of 71 years (range, 65–82 years). Severe CRAE incidence in patients with low, medium, or high CARG risk was 27%, 54%, and 71%, respectively (p = 0.026). The incidence of severe non-hematological toxicities was 5%, 35%, and 64%, respectively (p < 0.01). There was no association between age or ECOG PS and chemotherapy toxicity. The results suggest the validity of the CARG predictive tool in elderly cancer patients with prior anticancer therapy. Particularly, the tool showed potential for predicting non-hematological toxicity.

Multi-institutional feasibility study of intensity-modulated radiotherapy with chemotherapy for locally advanced non-small cell lung cancer.

This multi-institutional clinical trial evaluated the feasibility of intensity-modulated radiotherapy (IMRT) for patients with locally advanced non-small cell lung cancer (NSCLC). The major inclusion criteria were clinical stage III NSCLC, age 20-74years, and Eastern Cooperative Oncology Group performance status 0-1. Patients were treated with either cisplatin + S-1 (CS; four cycles every 4weeks) or carboplatin + paclitaxel (CP; administered weekly with thoracic radiotherapy [RT], plus two consolidation cycles) concurrently with IMRT (60Gy in 30 fractions). The primary endpoint was a treatment completion rate, defined as at least two cycles of CS or five cycles of CP during IMRT and completing 60Gy IMRT within 56days after the start of treatment, assumed its 90% confidence interval exceeds 60%. RT quality assurance was mandatory for all the patients. Twenty-two patients were registered. One patient withdrew due to pulmonary infection before starting treatment. RT plans were reviewed and none was judged as a protocol violation. Grade 2 and 3 pneumonitis occurred in four (19%) and one (5%) patients, respectively. Seventeen patients met the primary endpoint, with a treatment completion rate of 77.3% (90% confidence interval [CI] 58.0%-90.6%). Four patients failed to complete chemotherapy due to chemotherapy-related adverse events, but 20 patients completed IMRT. There were no treatment-related deaths. The 2-year progression-free and overall survival rates were 31.8% (95% CI 17.3%-58.7%) and 77.3% (95% CI 61.6%-96.9%), respectively. The treatment completion rate did not meet the primary endpoint, but 20 of 22 patients completed IMRT.

Choline deficiency-related multi-omics characteristics are susceptible factors for chemotherapy-induced thrombocytopenia

The XELOX chemotherapy protocol that includes capecitabine and oxaliplatin is the routine treatment for colorectal cancer (CRC), but it can cause chemotherapy-related adverse events such as thrombocytopenia (TCP). To identify predictive biomarkers and clarify the mechanism of TCP susceptibility, we conducted integrative analysis using normal colorectal tissue (CRT), plasma, and urine samples collected before CRC patients received adjuvant XELOX chemotherapy. RNA-sequencing and DNA methylation arrays were performed on CRT samples, while liquid chromatography-mass spectrometry was performed on CRT, plasma, and urine samples. Differentially expressed features (DEFs) from each uni-omics analysis were then subjected to integrative analysis using Multi-Omics Factor Analysis (MOFA). Choline-deficiency in plasma and CRT was found as the most critical TCP-related feature. Based on bioinformatic analysis and literature research, we further concluded that choline-deficiency was the possible reason for most of the other TCP-related multi-omics DEFs, including metabolites representing reduced sphingolipid de novo synthesis and elevated solute carrier-mediated transmembrane transportation in CRT and plasma, DNA hypermethylation and elevated expression of genes involved in neuronal system genes. In terms of thrombocytopoiesis, these TCP-related DEFs may cause atypical maintenance and differentiation of megakaryocyte, resulting a suppressed ability of thrombocytopoiesis, making patients more susceptible to chemotherapy-induced TCP. At last, prediction models were developed and validated with reasonably good discrimination. The area under curves (AUCs) of training sets were all > 0.9, while validation sets had AUCs between 0.778 and 0.926. In conclusion, our results produced reliable marker systems for predicting TCP and promising target for developing precision treatment to prevent TCP.

Changes in body composition during neoadjuvant platinum-based chemotherapy associations prior to radical cystectomy: Implications for chemotherapy-associated adverse events and oncologic outcomes.

476 Background: Low skeletal muscle index (SMI) is associated with an increased risk of mortality in muscle-invasive bladder cancer (MIBC) and chemotherapy-related adverse events (AE) across numerous other malignancies. Small case series suggest neoadjuvant chemotherapy (NAC) is associated with a significant decline in SMI in patients with MIBC. However, limited data exists regarding changes in fat mass during NAC. Herein, we examine changes in SMI, visceral fat index (VFI), and subcutaneous fat index (SFI) in patients receiving NAC for MIBC before radical cystectomy (RC). We describe associations between body composition changes and NAC-associated AE and all-cause mortality (ACM) in patients with MIBC. Methods: Retrospective review of patients with MIBC (≥pT2 N0/x/1 M0) who received NAC (2006-2019). Patients with digitized abdominal computed tomography scans (CT) within 75 days prior (T1) and 75 days following completion (T2) of NAC were included. We segmented and calculated the indices (cm2/m2) for SMI, VFI, and SFI at the third lumbar vertebra level at T1 and T2 using validated methodology. Associations with AE during NAC and ACM were evaluated with multivariate logistic regression and Cox proportional hazards models. Results: Included 170 patients, median age 63 years receiving a median of 4 (IQR 3-5) cycles of Gemcitabine/Cisplatin (52%), MVAC (28%), or other NAC (20%). Absolute and relative changes in SMI, VFI, and SFI over a median of 112 days (IQR 94-146) between measurements are presented in the Table. 117 (69%) patients experienced grade ≥3 chemotherapy-related AE. No associations between baseline body composition or change in body composition during NAC with chemotherapy-related AE. T1 SMI (HR: 0.98; 0.97-0.99, p = 0.008), as well as T2 SMI (HR: 0.98; 0.96-0.99, p = 0.003), T2 VFI (HR: 0.99; 0.99-1.0, p = 0.05) and T2 SFI (HR: 0.99; 0.98-1.0, P = 0.03) were associated with ACM after adjusting for age, clinical T and N stage, and performance status. Conclusions: Patients undergoing NAC prior to RC experienced a 6.4% decrease in SMI and a 5.2% decrease in VFI during an average of 112 days. Chemotherapy-related AE were not associated with a change in body composition. Baseline SMI and T2 SMI, SFI, and VFI were associated with ACM on multivariable analysis. Future work is needed to understand the mechanisms underpinning such changes and the extent to which potentially detrimental changes in body composition may be mitigated before surgery.[Table: see text]