Chemotherapy-related Adverse Events Research Articles

A randomized, controlled, multicenter study of nab-paclitaxel plus cisplatin followed by surgery versus surgery alone for locally advanced esophageal squamous cell carcinoma (ESCC).

310 Background: Taxane is one of the commonly used chemotherapy drugs for ESCC. Nab-paclitaxel, a small particle albumin-bound form of paclitaxel, showed potentially efficacy in metastatic ESCC. This randomized, controlled, multi-center study is conducted to evaluate the efficacy and safety of nab-paclitaxel plus cisplatin in neoadjuvant treatment of ESCC. Methods: Two hundred and two patients with resectable locally advanced ESCC which was located in the middle or lower third of the esophagus were enrolled and randomly assigned in a 1:1 ratio to receive neo-adjuvant chemotherapy or surgery alone. Patients were treated with either two 3-week cycles of nab-paclitaxel (125mg/m2, iv, d1, 8) and cisplatin (75mg/m2, iv, d1), followed by esophagectomy 4-6 weeks after neoadjuvant (the treatment arm) or directly underwent esophagectomy (the control arm). The primary endpoint was overall survival (OS), the secondary endpoints included 1-, 2-, and 3-year OS rate, 1-, 2-, and 3-year disease-free survival (DFS) rate, R0 resection rate, reduction stage rate, chemotherapy-related adverse events. Results: Between April 2019 and June 2021, we randomly assigned 67 patients, of whom 31 in the treatment arm and 33 in the control arm were analyzed. There was no difference in baseline characteristics between the two arms. In the treatment arm, 24 patients underwent R0 resection, and 2 did not undergo surgery although chemotherapy was completed. All patients in control arm underwent R0 resection. In the treatment arm, the pathological complete response (pCR) rate was 20.83%, the major pathological response (mPR) rate was 33.33%, and the down-staging rate was 58.33%. No difference in survival benefit was observed between the two arms. The 1- and 2-year DFS rates of the treatment arm and the control arm were 88.99% vs 75.58% (HR = 0.421, 95%CI: 0.087̃2.032, P = 0.281) and 88.99% vs 66.13% (HR = 0.387, 95%CI: 0.082̃1.833, P = 0.231), respectively. The 1-year and 2-year OS rates of the treatment arm and control arm were 93.21% vs 75.32% (HR = 0.293, 95%CI: 0.061̃1.409, P = 0.125) and 86.56% vs 75.32% (HR = 0.444, 95%CI: 0.115̃1.716, P = 0.239). The neoadjuvant chemotherapy was well tolerated. According to NCI-CTC AE V.5.0, the most common adverse events were hematological toxicity, including neutropenia (16.13%), anemia (3.23%) and hypoproteinemia (3.23%), no grade IV adverse events occurred. Conclusions: Nab-paclitaxel plus cisplatin for ESCC reveals a promising efficacy and safety, and has a tendency to prolong DFS and OS compared with surgery alone. The long-term results are worthy of further exploration. Clinical trial information: NCT03964753.

Induction Chemotherapy Followed by Primary Tumor Resection Did Not Bring Survival Benefits in Colon Cancer Patients With Asymptomatic Primary Lesion and Synchronous Unresectable Metastases.

BackgroundIt is still controversial whether primary tumor resection (PTR) improves survival in colorectal cancer (CRC) patients with unresectable metastases.MethodsColon cancer patients were enrolled and randomly allocated to with or without PTR after induction chemotherapy with XELOX or mFOLFOX6, and those with chemotherapy failure were excluded. The primary endpoint was TTF (time to strategy failure) on an intent-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02291744.ResultsBetween April 2015 and July 2020, 140 patients were enrolled, and 54 patients were excluded due to colon obstruction (16), perforation (1), disease progression (22), death (1), radical resection (3), or other reasons (11). After induction chemotherapy, 86 patients were randomized into group A (the resection group, n = 42) or group B (chemotherapy-alone group, n = 44). The median TTF was 143 days (95% CI: 104.9–181.1) in group A and 196 days (95% CI: 96.5–295.5) in group B (HR: 0.930 95% CI: 0.589–1.468, p = 0.755), and there was no significant difference in PFS, OS, and incidence of chemotherapy-related adverse events between two groups. The primary lesion-related events after PTR in group A were significantly fewer than those in group B. Patients with a tumor regression grade (TRG) score of 2 had longer TTF and PFS than those with score of 3.ConclusionPTR after induction chemotherapy could not bring survival benefits for colon cancer patients with unresectable metastases, and it is not recommended routinely. However, it also requires individualized treatment as colon obstruction or perforation occurred in some patients and PTR could reduce primary tumor-related events, and the TRG score might help for selection of beneficial patients.

Adolescents' understanding of chemotherapy-related adverse events: a concept elicitation study.

to document adolescents' understanding of chemotherapy-related core adverse events from the Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events and thus begin the validation process of this tool's items with Brazilian adolescents. this is a prospective, qualitative study of concept elicitation. The participants were 17 adolescents aged 13-18 years and undergoing chemotherapy in three hospitals in São Paulo - SP, Brazil. Cognitive interviews were conducted with questions based on chemotherapy-related adverse events. Data were analyzed for responsiveness and missingness. adolescents could and were willing to provide descriptive information about their chemotherapy adverse events, including physical and emotional events. Some participants suggested alternative terms to name the adverse events and some used more complex terms, but most were satisfied with the primary terms used by the researchers. this study represents the first steps towards understanding how adolescent cancer patients identify, name, and describe these events by cognitive interviewing to help design future assessment instruments focused on this age group. (1) Adolescents' voice is a priority in reporting chemotherapy-related adverse events. (2) Adverse events (AEs) inquiry may best be initiated with open-ended questions. (3) Elicitation studies can include the voices of the target population. (4) Adolescents with cancer can self-report clinically relevant chemotherapy AEs.

Adolescents’ understanding of chemotherapy-related adverse events: a concept elicitation study

Resumen Objetivo: documentar la comprensión de los adolescentes de los principales eventos adversos relacionados con la quimioterapia a partir de la versión de los Criterios Terminológicos Comunes para Eventos Adversos reportados por los pacientes pediátricos y así iniciar el proceso de validación de los ítems de esta herramienta con adolescentes brasileños. Método: este es un estudio prospectivo y cualitativo de elicitación de conceptos. Los participantes fueron 17 adolescentes de entre 13 y 18 años de edad que recibían quimioterapia en tres hospitales de São Paulo-SP, Brasil. Se realizaron entrevistas cognitivas con preguntas basadas en eventos adversos relacionados con la quimioterapia. Los datos se analizaron en función de la presencia y ausencia de respuesta. Resultados: los adolescentes podían y estaban dispuestos a proporcionar información descriptiva sobre los efectos adversos de la quimioterapia, incluidos los físicos y emocionales. Algunos participantes sugirieron términos alternativos para denominar los eventos adversos y otros utilizaron términos más complejos, pero la mayoría se mostró satisfecha con los términos principales utilizados por los investigadores. Conclusión: este estudio representa los primeros pasos hacia la comprensión de cómo los pacientes adolescentes con cáncer identifican, nombran y describen estos eventos mediante entrevistas cognitivas para ayudar a diseñar futuros instrumentos de evaluación centrados en este grupo de edad.

Effectiveness of oral fluoropyrimidine monotherapy as adjuvant chemotherapy for high-risk stage II colon cancer.

PurposeThe benefit of adjuvant chemotherapy for stage II colon cancer has not been clearly demonstrated even in cases with high-risk factors. This study aimed to compare the effectiveness of oral fluoropyrimidine monotherapy as adjuvant chemotherapy with that of intravenous fluoropyrimidine-based chemotherapy for high-risk stage II colon cancer.MethodsThis single-institution, retrospective study included patients who underwent curative resection for high-risk stage II colon cancer between 2003 and 2014. Patients were classified into 3 postoperative treatment groups: observation, oral fluoropyrimidine monotherapy group (OG), or intravenous fluoropyrimidine-based chemotherapy group (IVG).ResultsWe identified 356 patients, including 87 (24.4%) in the observation group, 172 (48.3%) in the OG, and 97 (27.2%) in the IVG. Patients in the OG were older (63.8 ± 10.7 vs. 56.5 ± 10.8, P < 0.001) and had a lower number of T4 lesions (12.8% vs. 35.1%, P < 0.001) than those in the IVG. Regarding survival outcomes, the 5-year overall and disease-free survival rates were not different between the OG and IVG (91.2% vs. 92.6% [P = 0.090] and 85.1% vs. 81.9% [P = 0.535], respectively). In multivariate analysis, age over 70 years and no adjuvant chemotherapy were associated with poor overall survival and disease-free survival. Fewer chemotherapy-related adverse events of grade ≥3 were observed in the OG than in the IVG (12.2% vs. 34.0%, P < 0.001).ConclusionIn high-risk stage II colon cancer, adjuvant oral fluoropyrimidine monotherapy can be an effective and convenient alternative to intravenous fluoropyrimidine-based chemotherapy as it has comparable oncological outcomes and reduced chemotherapy-related complications.

Adolescents’ understanding of chemotherapy-related adverse events: a concept elicitation study

Resumo Objetivo: documentar a compreensão dos adolescentes sobre os principais eventos adversos relacionados à quimioterapia a partir da versão Pediátrica dos Desfechos Relatados pelo Paciente (Patient-Reported Outcomes) dos Critérios de Terminologia Comum para Eventos Adversos (Common Terminology Criteria for Adverse Events), e assim iniciar o processo de validação dos itens desta ferramenta com adolescentes brasileiros. Método: trata-se de um estudo prospectivo, qualitativo, de elicitação de conceitos. Participaram do estudo 17 adolescentes de 13 a 18 anos, submetidos à quimioterapia em três hospitais da cidade de São Paulo-SP, Brasil. Foram realizadas entrevistas cognitivas com perguntas baseadas em eventos adversos relacionados à quimioterapia. Os dados foram analisados quanto à responsividade e ausência de resposta. Resultados: os adolescentes puderam e estavam dispostos a fornecer informações descritivas sobre seus eventos adversos quimioterápicos, incluindo eventos físicos e emocionais. Alguns participantes sugeriram nomes alternativos para os eventos adversos e alguns usaram termos mais complexos, mas a maioria ficou satisfeita com aqueles utilizados pelos pesquisadores. Conclusão: este estudo representa os primeiros passos para entender como os adolescentes com câncer identificam, nomeiam e descrevem esses eventos por meio de entrevistas cognitivas para ajudar a criar futuros instrumentos de avaliação focados nessa faixa etária.

Cost-Effectiveness of Pembrolizumab Versus Carboplatin and Paclitaxel in Patients With Unresectable or Metastatic Melanoma After First-Line Treatment in China

ObjectiveThis study aimed to evaluate the cost-effectiveness of pembrolizumab compared with standard-of-care chemotherapy (paclitaxel + carboplatin [PC]) in patients with unresectable or metastatic melanoma after first-line treatment from a Chinese healthcare system perspective. MethodsWe conducted a partitioned-survival model with a 1-week cycle length and a 20-year base-case time horizon. Piecewise parametric models were fitted to KEYNOTE-006 trial data to estimate progression-free survival and overall survival for pembrolizumab, and a network meta-analysis was used to estimate the clinical outcomes for standard of care. Quality-adjusted life-years (QALYs) were calculated using EQ-5D data from KEYNOTE-006, applying Chinese-specific utility tariffs. Costs included drug acquisition, administration, adverse events, and disease management, reflecting the Chinese pricing system. Chinese-specific disease management costs were estimated based on clinical opinion on health state resource use and chemotherapy-related adverse events. Costs and outcomes were discounted at 5% annually. Multiple deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results. ResultsIn the base-case analysis, the treatment of pembrolizumab is estimated to yield 2.63 life-years (LYs) and 2.24 QALYs at an incremental cost of ¥372 316.46 versus PC. The incremental costs per LY and per QALY were ¥141 771.00 and ¥165 865.69, respectively, the latter being below a threshold of 3 times the per capita gross domestic product (￥193 932) in China, deemed as cost-effective according to the World Health Organization threshold. These findings were robust against a wide range of sensitivity analyses. ConclusionsPembrolizumab is projected as cost-effective compared with PC in patients with unresectable or metastatic melanoma after first-line treatment in China.

DNA-PK inhibition by M3814 enhances chemosensitivity in non-small cell lung cancer

A significant proportion of non-small cell lung cancer (NSCLC) patients experience accumulating chemotherapy-related adverse events, motivating the design of chemosensitizating strategies. The main cytotoxic damage induced by chemotherapeutic agents is DNA double-strand breaks (DSB). It is thus conceivable that DNA-dependent protein kinase (DNA-PK) inhibitors which attenuate DNA repair would enhance the anti-tumor effect of chemotherapy. The present study aims to systematically evaluate the efficacy and safety of a novel DNA-PK inhibitor M3814 in synergy with chemotherapies on NSCLC. We identified increased expression of DNA-PK in human NSCLC tissues which was associated with poor prognosis. M3814 potentiated the anti-tumor effect of paclitaxel and etoposide in A549, H460 and H1703 NSCLC cell lines. In the four combinations based on two NSCLC xenograft models and two chemotherapy, we also observed tumor regression at tolerated doses in vivo. Moreover, we identified a P53-dependent accelerated senescence response by M3814 following treatment with paclitaxel/etoposide. The present study provides a theoretical basis for the use of M3814 in combination with paclitaxel and etoposide in clinical practice, with hope to aid the optimization of NSCLC treatment.

A Collaborative Pharmacist-Physician Multi-Professional Pre-Chemotherapy Assessment in Hematology Cancer Patients Is an Efficient & Cost-Effective Model for Service Delivery of Outpatient Systemic Anti-Cancer Therapy (SACT)

IntroductionIncreasing complexity of cancer care has resulted in a paradigm shift from individual clinician-based to a larger multidisciplinary team approach. Expectantly the chemotherapy specialist pharmacist role in delivering such complex therapies will fall short of demand in current care delivery models & has expanded beyond dispensing medications & medication counseling. The UK National Cancer Vanguards have proposed models of care in order to enhance clinical chemotherapy services' performance thereby improving cancer patient outcomes & experience. These incorporate 2 principal themes; Medicines Optimization & development of an integrated team approach. We applied these 2 concepts by devising a joint Pharmacist-Physician Multiprofessional Team (MPT) clinic to achieve such objectives.MethodsWe prospectively piloted a newly designed Pharmacist-Physician MPT clinic. The aim is to determine the impact of adjunct pharmacist input as a model of care for outpatient pre-SACT assessment in lymphoma & myeloma patients (pts). An age- & sex-matched patient cohort receiving corresponding SACT assessed by single-handed clinicians in outpatient clinics during the same time-frame was used as the control cohort. The following data were collected: (1) prevalence of adverse events (AE) as per Common Terminology Criteria for AE version 4.03 & their outcomes upon intervention, (2) prevalence of unnecessary/potentially inappropriate prescriptions (U/PIP) & polypharmacy (PP) & (3) clinic & chemotherapy administration waiting times. Patient experience surveys based on the National Health Service (NHS) England Chemotherapy Patient Experience Survey (CPES) with added purpose-specific questionnaires were included to measure pts' perspectives, expectations & satisfaction. Descriptive statistics were calculated by using Fisher's exact test, Chi2 test for categorical variables & rank-sum analysis for continuous variables. Financial metrics were collected in retrospect to track downstream revenue with the following benchmarks: (1) Any delay beyond 60 minutes in any of the waiting times incurs £2.4/hour surcharge on the patient & an average £30/hour on the Hospital Trust per patient, (2) MPT attendance is priced higher than single professional counterpart (£171 versus (vs) 109) as per 2017/18 NHS National Tariff Payment System.ResultsA total of 82 pts (127 visits; median 1, range 1-5) were reviewed in the MPT clinic between 01-31-17 & 07-11-17; mean age 62 (25-82) years, 52% were women & 88% had lymphoma. The control cohort included 81 pts; median age 63 (26-79) years, 55% were women & 91% had lymphoma. 27 pts in the MPT group reported grade ≥2 AE vs 37 control pts; AE grades 2, 3 & 4 were recorded in 17, 9 & 1 pts vs 26, 11, 0 pts, respectively; p=.038. All pts evaluated in the MPT clinic experienced an improvement in AE by at least 1 grade & 15 pts achieved complete recovery with intervention. In the control group, 8 pts had no improvement in AE grade with 7 pts achieving complete recovery with intervention; p=.03. Prevalence of U/PIP, PP (≥5 & <10 medications) & excessive PP (≥10 medications) use were 11% (n=9), 6.1% (n=5) & 1.2% (n=1) in the MPT clinic & 20.7% (n=17), 12.2% (n=10) & 2.4% (n=2) in the controls; p<.001. Clinic waiting times were significantly shorter in the MPT clinic; median <30 min vs 1-2 hours, p<.001. Chemotherapy administration waiting time was also shorter in the MPT clinic; median 20 min (-20-150) vs 54 min (0-188), p=.008, with 82% of those reviewed at MPT being <60min vs 45% in the control; p=.001. With 1027 pre-SACT reviews recorded during the study period, MPT clinic would offer a minimum cost-saving of £16,945 & £63,674 profit. Eighty pts (40 from each group) completed the CPES. Key patient satisfaction metrics were significantly superior with MPT reviews, namely shorter clinic waiting times (p<.001), better understanding of progress (p=.0135), enhanced AE evaluation (p=.0325) & provision of advice/support in dealing with them which translated into subjective improvement in toxicity profile (p=.04).ConclusionA collaborative pharmacist-physician MPT approach has demonstrated significant improvement in chemotherapy-related AE, reduced waiting times, enhanced patient experience & translated to cost-savings to pts & the hospital. It has provided a proof of concept for a more robust, efficient & cost-effective model for cancer care delivery but also a platform for revenue generation. DisclosuresNo relevant conflicts of interest to declare.

Clinical efficacy and safety of early adjuvant chemotherapy for stage III colon cancer: Short-term outcomes of a multicenter, randomized, open-label, phase 3 trial.

3598 Background: Adjuvant chemotherapy (AC) is recommended to commence within 8 weeks since after surgical resection of stage II or III colon cancer. Results of many retrospective studies showed inferior survival outcomes following delay of AC delay. Moreover, preclinical studies showed that the progression of disseminated cancer cells is profound during the postoperative period. This study is the first prospective trial to evaluate early (≤ 14 days postoperative) AC for patients (pts) with stage III colon cancer. Methods: This study is a prospective, multicenter, randomized phase III trial. Pts with pathological stage III colon cancer were enrolled and randomized 1:1 to early AC (starting AC ≤ 14 days after surgery) or conventional AC (starting AC &gt; 14 days after surgery). Pts were recommended to receive 12 cycles of FOLFOX-6 for AC. The primary endpoint was disease-free survival. The secondary endpoints were overall survival, adverse events, surgical complication during AC, and patient-reported outcomes (quality of life) during 1 year after surgery. Herein, safety data, chemotherapy delivery, and quality of life are presented. Results: This study randomized 443 pts either early AC arm (221pts) or early AC arm (222 pts) to the during September 2011 to March 2020. 380 pts who received at least one cycle of FOLFOX-6 were included in the safety analysis (192 and 188 in the early and conventional AC arms, respectively). The baseline characteristics of the two groups were well-balanced except for the interval from the surgery to the initial AC. The early and conventional AC arms started their first chemotherapy at median of 13 (4-43 days) and 29 (17-53 days) after surgery (p &lt; 0.001), respectively. No significant differences were seen in the median chemotherapy cycles, AC completion, and relative oxaliplatin dose intensity between groups. AC Completion without any change of dose or schedule delay was seen in 18% and 20% in early and conventional AC arms respectively, while dose reduction or delay was 65% and 61%, respectively. Toxicities of grade 3 or more were seen in 28% in both groups. One patient in the early AC arm underwent an emergent operation for anastomotic leakage on the second day of 5-fluorouracil infusion (postoperative day 14). However, the surgical complication was not seen in any other patient. The scores of the European Organization for Research and Treatment of Cancer Quality of Life core 30 questionnaire were similar in both arms at baseline (before starting AC), and 1 month, 3 months, 6 months, and 12 months after surgery. Conclusions: Early AC was safe and did not increase either chemotherapy-related adverse events or surgery-related complications during treatment. Moreover early AC did not reduce the quality of life of the pts during 1 year after surgery. This study continues to follow-up the patients for survival outcomes. Clinical trial information: NCT01460589.

Real-world safety and medication use of second-line (2L) 5-fluorouracil (5-FU)–based regimens among patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC).

e16248 Background: Chemotherapy-related adverse events (AEs) can negatively impact the treatment of pts. Managing and preventing these toxicities often require additional medications. This study examined the proportion of pts with mPDAC treated with 5-FU–based regimens in 2L who experienced AEs during treatment, and the proportion who received medication to manage those AEs. Methods: Data were extracted for pts diagnosed with mPDAC who initiated 2L treatment Jan 2016 to Aug 2020 from the Flatiron Health database. Pts included were treated with FOLFIRINOX (FFX), FOLFOX, FOLFIRI, or liposomal irinotecan (nal-IRI). The occurrence of grade 3 (G3) and grade 4 (G4) neutropenia and G3/G4 thrombocytopenia were determined using lab results and the grading criteria from the CTCAE v4.03. The occurrence of diarrhea and nausea/vomiting (N/V) were identified via ICD-10-CM codes. The use of atropine and granulocyte colony stimulating factor (G-CSF) during treatment was assessed. Duration of therapy (DOT) was assessed for each regimen. Descriptive statistics for AEs, medication use, and DOT were reported. Results: Of the 825 eligible pts, 29.0% (n=239) received FFX, 40.2% (n=332) received regimens containing nal-IRI, 24.0% (n=198) received FOLFOX, and 6.8% (n=56) received FOLFIRI. The median DOT (IQR) was 15.1 weeks (wks) (7.1 – 30.1), 12.9 wks (6.0 – 24.8), 11 wks (6.4 – 24.0), and 12.7 wks (8.3 – 24.6) for pts who received FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. G3/G4 thrombocytopenia (&lt;50,000/mm3) presented in 9.6%, 2.4%, 8.1%, and 14.3% of pts treated with FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. G3/G4 neutropenia (&lt;1000/mm3) presented in 22.6%, 12.3%, 14.6%, and 19.6% of pts treated with FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. The median (Q1-Q3) cumulative dose of the G-CSF pegfilgrastim was 18mg (12 – 45), 18mg (12 – 48), 24mg (12 – 36), and 30mg (13 – 48) for pts treated with FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. Atropine use was higher in pts treated with FFX and FOLFIRI (90.8% and 94.6%, respectively) than for pts treated with nal-IRI (75.6%). The full study results are reported in the table. Conclusions: In this study of AEs among pts with mPDAC treated in 2L, pts who received liposomal irinotecan had the lowest proportion of thrombocytopenia and neutropenia. Diarrhea was similar across the cohorts despite the high proportion of use in atropine for pts treated with FFX and FOLFIRI.[Table: see text]

Genetic polymorphism in ATIC is associated with effectiveness and toxicity of pemetrexed in non-small-cell lung cancer

Patients with advanced non-small-cell lung cancer who are treated with pemetrexed display a wide variation in clinical response and toxicity. In this prospective, multicentre cohort study, we investigated the association...

Polymorphism of FGD4 and myelosuppression in patients with esophageal squamous cell carcinoma.

Background: Chemotherapy-related adverse events may restrain taxane/cisplatin administration as a regimen for patients with esophageal squamous cell carcinoma. Genetic polymorphisms may contribute to adverse event susceptibility. Method & results: The authors genotyped ten SNPs from five genes (rs1045642, rs2032582 and rs3213619 of ABCB1; rs2231137 and rs2231142 of ABCG2; rs246221 of ABCC1; rs3740066 of ABCC2; and rs10771973, rs12296975 and rs1239829 of FGD4) in 219 patients with esophageal squamous cell carcinoma treated with taxane/cisplatin. Patients with severe toxicities were compared with those with minor or no adverse events by unconditional logistic regression models and semi-Bayesian shrinkage. After adjustment for age and sex, with the null prior, FGD4 rs1239829 was statistically significantly related to grade 3-4 leukopenia (odds ratio [95% CI] in dominant model=1.77 [1.04-3.03]). Conclusion: The minor allele of FGD4 rs1239829 was related to grade 3-4 leukopenia in patients with esophageal squamous cell carcinoma treated with taxane/cisplatin, with unclear biological mechanism.

Safety and effectiveness of oxaliplatin combined with capecitabine or oxaliplatin combined with S-1 neoadjuvant chemotherapy in the treatment of advanced gastric cancer

Objective: To explore the safety and efficacy of oxaliplatin plus capecitabine (CapeOX) or oxaliplatin plus S-1 (SOX) regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer. Methods: A retrospective cohort study was performed. Clinical data of patients diagnosed as advanced gastric cancer undergoing CapeOX/SOX neoadjuvant chemotherapy and standard laparoscopic radical operation for gastric cancer in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from April 2016 to April 2019 were retrospectively collected. Inclusion criteria were as follows: (1) age≥18 years; (2) gastric adenocarcinoma was confirmed by histopathology and the clinical stage was T3-4aN+M0; (3) tumor could be resectable; (4) preoperative neoadjuvant chemotherapy was CapeOX or SOX regimen without radiotherapy or other regimen chemotherapy; (5) no other concurrent malignant tumor; (6) the Eastern Cooperative Oncology Group (ECOG) score ≤ 1; (7) no bone marrow suppression; (8) normal liver and kidney function. Exclusion criteria were as follows: (1) patients with recurrent gastric cancer; (2) patients receiving emergency surgery due to tumor perforation, bleeding, obstruction, etc.; (3) allergy to oxaliplatin, S-1, capecitabine or any drug excipients; (4) diagnosed with coronary heart disease, cardiomyopathy, or the New York Heart Association class III or IV; (5) pregnant or lactating women. A total of 118 patients were enrolled as the neoadjuvant chemotherapy group, and 379 patients with locally advanced gastric cancer who received surgery combined with postoperative adjuvant chemotherapy over the same period simultaneously were included as the adjuvant chemotherapy group. After propensity score matching was performed including gender, age, ECOG score, tumor site, clinical stage, chemotherapy regimen and other factors by 1:1 ratio, there were 40 cases in each group. The differences between the two groups in general conditions, efficacy of neoadjuvant chemotherapy, intraoperative conditions, postoperative conditions, histopathological results, chemotherapy-related adverse events, and survival status were compared and analyzed. Results: Comparison of baseline demographics between the two groups showed no statistically significant difference (all P>0.05). In the neoadjuvant chemotherapy group, 5.0% (2/40) of patients achieved clinical complete response, 57.5% (23/40) achieved partial response, 32.5% (13/40) remained stable disease, and 5.0% (2/40) had disease progression before surgery. Objective response rate was 62.5% (25/40), and disease control rate was 95.0% (38/40). There were no statistically significant differences between neoadjuvant chemotherapy group and adjuvant chemotherapy group in terms of operation time, intraoperative blood loss, number of lymph node harvested, length of postoperative hospital stay, and postoperative mortality and morbidity (all P>0.05). Postoperative complications were well managed with conservative treatment. No Clavien-Dindo IV or V complications were observed in both groups. Pathological results showed that the proportion of patients with pathological stage T1 in the neoadjuvant chemotherapy group was significantly higher than that in the adjuvant chemotherapy group [27.5% (11/40) vs. 5.0% (2/40)], while the proportion of patients with pathological stage T3 was significantly lower than that in the adjuvant chemotherapy group [20.0% (8/40) vs. 45.0% (18/40)], with statistically significant difference (χ(2)=15.432, P=0.001). In the neoadjuvant chemotherapy group, there were 4 cases of tumor regression grade 0, 8 cases of grade 1, 16 cases of grade 2, and 12 cases of grade 3. The pathological complete response rate was 10% (4/40), the overall pathological response rate was 70.0% (28/40). There was no statistically significant difference in the incidence of chemotherapy-related adverse events between neoadjuvant chemotherapy group and adjuvant chemotherapy group [40% (16/40) vs. 37.5% (15/40), P>0.05). There were no statistically significant differences in OS (43 months vs. 40 months) and 3-year OS rate (66.1% vs. 59.8%) between neoadjuvant chemotherapy group and adjuvant chemotherapy group (P=0.428). The disease-free survival (DFS) and 3-year DFS rates of the neoadjuvant chemotherapy group were significantly superior to those of the adjuvant chemotherapy group (36 months vs. 28 months, 51.4% vs. 35.8%, P=0.048). Conclusion: CapeOX or SOX regimen neoadjuvant chemotherapy is a safe, effective and feasible treatment mode for advanced gastric cancer without increasing surgical risk and can improve the DFS of patients.

Safety and efficacy of adjuvant chemotherapy with oxaliplatin and S-1 for patients with locally advanced gastric cancer after D2 lymph nodes dissection

Objective: To investigate the safety and efficacy of oxaliplatin combined with S-1 (SOX) as adjuvant chemotherapy after D2 radical gastrectomy for locally advanced gastric cancer. Methods: A descriptive case series study was applied. Case inclusion criteria: (1) locally advanced gastric cancer confirmed by endoscopic biopsy or surgical specimen pathology as gastric adenocarcinoma; (2) receiving D2 radical gastric resection followed by SOX regimen adjuvant chemotherapy. Case exclusion criteria: (1) postoperative pathological TNM stage I or IV; (2) acute complications and emergency surgeries; (3) receiving neoadjuvant therapy; (4) concurrent malignancies and complications compromising patients' treatment or survival; (5) without receiving adjuvant SOX chemotherapy. A total of 94 patients with stage II-III gastric cancer who underwent D2 radical gastrectomy and postoperative adjuvant SOX chemotherapy at department of Gastrointestinal Surgery, Peking University People's Hospital from January 2014 to December 2019 were retrospectively enrolled. Chemotherapy-related adverse events, overall survival (OS) and progression-free survival (PFS) were analyzed. Kaplan-Meier survival analysis was performed and log rank test was used to analyze the difference between groups. P<0.2 or clinically significant indicators in univariate analysis were included in Cox regression model for multivariate survival analysis. Results: Among these 94 patients, there were 65 males and 29 females with an average age of (58.2±12.1) years; 33 patients with hypertension, diabetes mellitus, or cardiovascular and cerebrovascular diseases, 11 patients with family history of gastrointestinal tumors; 59 patients with tumors locating in the antrum or pylorus, 16 patients in the gastric body, 19 patients in the gastric fundus or cardia; 29 patients underwent total gastrectomy, 5 patients underwent proximal subtotal gastrectomy, and 60 patients underwent distal subtotal gastrectomy. In this study, 73 patients (77.7%) completed at least 5 cycles of adjuvant SOX regimen chemotherapy. Grade 3-4 adverse reactions included thrombocytopenia (23.4%, 22/94), nausea and vomiting (18.1%, 17/94) and peripheral neurotoxicity (6.4%, 6/94). Eighty-nine patients (94.7%) completed follow-up with a median follow-up time of 32 months. The 3-year and 5-year OS rates were 89.8% and 83.7%, respectively, and the 3-year and 5-year PFS rates were 81.4% and 78.1%, respectively. Taking 5 chemotherapy cycles as the cut-off point, the 3-year OS rate and 3-year PFS rate were 72.2% and 53.9% in the adjuvant chemotherapy < 5 cycles group, and 93.7% and 87.1% in the adjuvant chemotherapy ≥5 cycles group, respectively; the differences were statistically significant (P=0.029, P=0.006). Univariate analysis showed that the adjuvant chemotherapy < 5 cycles group was associated with worse 3-year OS (P=0.029). Multivariate analysis showed that insufficient chemotherapy cycle (HR=9.419, 95% CI: 2.330-38.007, P=0.002) was an independent risk factor for 3-year OS. Meanwhile, univariate analysis showed that the adjuvant chemotherapy <5 cycles (P=0.006), preoperative CEA > 4.70 μg/L (P=0.035) and adjacent organ resection (P=0.024) were associated with worse 3-year PFS. Multivariate analysis showed that adjuvant chemotherapy <5 cycles (HR=10.493, 95% CI: 2.466-44.655, P=0.001) and adjacent organ resection (HR=127.518, 95% CI: 8.885-1 830.136, P<0.001) were independent risk factors for 3-year PFS. Conclusions: Oxaliplatin combined with S-1 as an adjuvant chemotherapy regimen for locally advanced gastric cancer has high efficacy and low incidence of adverse reactions. At least 5 cycles of SOX regimen adjuvant chemotherapy can significantly improve prognosis of patients with stage II-III gastric cancer.

The prognostic impact of tumour location and first-line chemotherapy regimen in locally advanced pancreatic cancer.

The prognostic impact of tumour location (pancreatic head vs. pancreatic body/tail) and first-line chemotherapy regimen (gemcitabine plus nab-paclitaxel vs. modified FOLFIRINOX) has not been fully elucidated in locally advanced pancreatic cancer. Therefore, we conducted this study to examine the prognostic impact of tumour location and first-line chemotherapy regimen. We retrospectively investigated locally advanced pancreatic cancer patients who initiated first-line chemotherapy (gemcitabine plus nab-paclitaxel or modified FOLFIRINOX) between March 2014 and December 2019. We compared clinical characteristics and survival outcomes according to chemotherapy regimen and tumour location. Furthermore, we examined the prognostic factors associated with overall survival using cox proportional hazards model. Distant metastasis pattern was also compared according to tumour location. A total of 128 patients were included (GnP 95, mFFX 33; Ph 66, Pbt 62). Distribution of chemotherapy regimen was balanced between pancreatic head and pancreatic body/tail cancers. Eight patients underwent conversion surgery and 81 patients (63%) developed distant metastasis. Although patients receiving modified FOLFIRINOX were significantly younger and tended to have better performance status compared to patients receiving gemcitabine plus nab-paclitaxel, radiological tumour response, progression-free survival, overall survival and chemotherapy-related adverse events were similar between the two groups except for grades 3-4 anorexia (9% vs. 1%, P=0.05). Furthermore, overall survival was similar between pancreatic head and pancreatic body/tail cancers. Conversion surgery and radiation therapy were identified as independent prognostic factors for overall survival. The most common site of distant metastasis was liver metastasis in both groups and pattern of distant metastasis was not different between the two groups. In our experience, tumour location and first-line chemotherapy regimen were not a prognostic factor for overall survival in locally advanced pancreatic cancer.

Real-world safety data and differentiation of second-line (2L) 5-fluorouracil (5-FU) based regimens among patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).

390 Background: Chemotherapy related adverse events (AEs) can impact the treatment of patients, reducing quality of life and leading to dose delays and treatment discontinuation. This study examined the proportion of patients (pts) with mPDAC treated with 5-FU-based regimens in the 2L setting who experienced AEs during treatment. Methods: Data were extracted for pts diagnosed with mPDAC who initiated 2L treatment between January 2016 and July 2020 from the Flatiron Health electronic health database. Pts included in the study were treated with FOLFIRINOX (FFX), FOLFOX, FOLFIRI, or a regimen containing liposomal irinotecan. The occurrence of grade 3 (G3) and grade 4 (G4) neutropenia, G3/G4 elevated alanine transaminase (ALT) and anemia where transfusion was indicated were determined using lab results and the grading criteria from the Common Terminology Criteria for Adverse Events v4.03. The occurrence of diarrhea, fatigue, nausea and vomiting (N/V), and neuropathy were identified from structured diagnosis records through ICD-10-CM codes. Duration of therapy (DOT) was assessed for each regimen. Descriptive statistics for AEs and DOT were reported. Results: Of the 804 pts included in the study, 28.4% (n=228) received FFX, 39.8% (n=320) received regimens containing liposomal irinotecan, 24.8% (n=199) received FOLFOX, and 7.1% (n=57) received FOLFIRI. The median DOT (IQR) was 86 days (d) (43 – 206), 79d (41 – 169), 72d (43 – 166), and 84d (46 – 148) for pts who received FFX, liposomal irinotecan, FOLFOX, and FOLFIRI, respectively. G3/G4 neutropenia (&lt;1000/mm3) presented in 28.1% (n=64) of pts treated with FFX, 11.9% (n=38) of pts treated with liposomal irinotecan, 17.1% (n=34) of pts treated with FOLFOX, and 36.8% (n=21) of pts treated with FOLFIRI. NV occurred in 14.9% (n=34), 13.1% (n=42), 12.6% (n=25), and 10.5% (n=6), respectively. The full AE results are summarized in the table. Conclusions: In this assessment of often dose-limiting AEs among pts with mPDAC treated in 2L, pts who received liposomal irinotecan had the lowest proportion of neutropenia. No clear pattern was noted for N/V, neuropathy, fatigue, anemia, and elevated ALT. Further research is necessary to determine the real-world cost implications of AEs in this patient population. [Table: see text]

Myosteatosis evaluation using erector spinae and psoas muscles to predict adverse events during adjuvant chemotherapy for breast cancer.

Myosteatosis (intramuscular adiposity) is predictive of chemotherapy toxicity in women undergoing adjuvant chemotherapy for breast cancer (BC). We evaluated a novel, user-friendly and cost-effective technique utilizing a Picture Archiving and Communication Systems (PACS) tool that is readily available in the electronic medical record (EMR), using skeletal muscle density (SMD) to detect myosteatosis and then compared PACS results with those derived from widely used body composition software (SliceOMatic, QC, Canada). Using retrospective data from a sample of women with early BC (Stage I-III) who had CT scan and received chemotherapy. Pearson correlation coefficients were used to compare SliceOMatic with PACS results. Associations of PACS results with chemotherapy-related adverse events were evaluated using multivariable (MV) log-binomial models adjusted for age, race, BMI, anthracycline-based therapy, and number of comorbidities. In 338 patients, mean age was 51, 32% were non-white, and 40% had obesity (BMI ≥ 30kg/m2). Correlation of SMD using SliceOMatic whole muscle measurements with PACS psoas muscle was 0.76 (p < .0001) and with PACS erector spinae muscle 0.91 (p < .0001). Using PACS psoas muscle, myosteatosis was associated with any adverse event [RR 1.66, CI 1.22-2.26 (p < .0001)], dose reduction [RR 1.63, CI 1.01-2.65 (p = .05)], and early treatment discontinuation [RR 2.14, CI 1.10-4.14 (p = 0.03)]. Using PACS erector spinae muscle, myosteatosis was associated any adverse event [RR 1.59, CI 1.11-2.27 (p = 0.01)] and dose reduction [RR 1.91, CI 1.07-3.42 (p = .03)]. Skeletal muscle density measures using PACS correlated strongly with SliceOMatic results and both are similarly predictive of chemotherapy-related adverse events.

FOLFOXIRI-Bevacizumab or FOLFOX-Panitumumab in Patients with Left-Sided RAS/BRAF Wild-Type Metastatic Colorectal Cancer: A Propensity Score-Based Analysis.

Doublets plus anti-epidermal growth factor receptors (EGFRs) are the preferred upfront option for patients with left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC). Initial therapy with FOLFOXIRI-bevacizumab is superior to doublets plus bevacizumab independently from primary tumor sidedness and RAS/BRAF status. No randomized comparison between FOLFOXIRI-bevacizumab versus doublets plus anti-EGFRs is available in left-sided RAS/BRAF wild-type mCRC. We selected patients with left-sided RAS and BRAF wild-type mCRC treated with first-line FOLFOX-panitumumab or FOLFOXIRI-bevacizumab in five randomized trials: Valentino, TRIBE, TRIBE2, STEAM, and CHARTA. A propensity score-based analysis was performed to compare FOLFOXIRI-bevacizumab with FOLFOX-panitumumab. A total of 185 patients received FOLFOX-panitumumab and 132 received FOLFOXIRI-bevacizumab. Median progression-free survival (PFS) and median overall survival (OS) were 13.3 and 33.1 months in the FOLFOXIRI-bevacizumab group compared with 11.4 and 30.3 months in the FOLFOX-panitumumab group (propensity score-adjusted hazard ratio (HR) for PFS, 0.82; 95% confidence interval (CI), 0.64-1.04; p = .11; propensity score-adjusted HR for OS, 0.80; 95% CI, 0.59-1.08; p = .14). No significant differences in overall response rate and disease control rate were observed. A statistically nonsignificant difference in favor of FOLFOXIRI-bevacizumab was observed for OS after secondary resection of metastases. Chemotherapy-related adverse events were more frequent in the FOLFOXIRI-bevacizumab group, with specific regard to grade 3 and 4 neutropenia (48% vs. 26%, adjusted p = .001). Although randomized comparison is lacking, both FOLFOXIRI-bevacizumab and FOLFOX-panitumumab are valuable treatment options in left-sided RAS/BRAF wild-type mCRC. A propensity score-based analysis of five trials was performed to compare FOLFOX-panitumumab versus FOLFOXIRI-bevacizumab in left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC). No significant differences were observed, but FOLFOXIRI-bevacizumab achieved numerically superior survival outcomes versus FOLFOX-panitumumab. Chemotherapy-related adverse events were more frequent in the FOLFOXIRI-bevacizumab group. These observations suggest that although doublet chemotherapy plus anti-EGFRs remains the preferred treatment in patients with left-sided RAS/BRAF wild-type mCRC, FOLFOXIRI-bevacizumab is a valuable option able to provide similar, if not better, outcomes at the price of a moderate increase in toxicity and may be adopted based on patients' preference and potential impact on quality of life.

Efficacy and safety of Prostate stereotactic body radiotherapy for metastatic castration-resistant prostate cancer: A prospective cohort study

BackgroundThe efficacy and safety of prostate SBRT in men with mCRPC is unknown. Materials and methodsA prospective cohort study was conducted with 125 men diagnosed with mCRPC. All patients received ADT plus chemotherapy. Patients were randomly assigned to receive daily prostate SBRT (36–48 Gy in 6–8 fractions). Patients who did not receive SBRT served as controls. ResultsThe primary endpoints were PFS and OS. After 89 months of total follow-up, the median PFS was 13.8 months in the SBRT group (n = 61) and 12.0 months in the control group (n = 64) (HR, 0.87; 95% CI, 0.61–1.24; P = 0.249). The OS was 25.7 months in the SBRT group and 23.8 months in the control group (HR, 0.93; 95% CI, 0.65–1.33; P = 0.230). A non-significant increase in the PSA response rate (50.8% vs. 43.7%) and time to PSA progression (8.3 months vs. 7.0 months) was observed in the SBRT group compared to the control group; however, the time to symptomatic progression was significantly prolonged in the SBRT group (11.3 months) compared to the control group (8.5 months) (HR, 0.76; 95% CI, 0.53–1.08; P = 0.019). There was an 11.5% incidence of radiation cystitis and radiation rectitis in the SBRT group, and the degree and incidence of hormone-related and chemotherapy-related adverse events were similar between the two groups. ConclusionAdding prostate SBRT significantly prolonged the time to symptomatic progression and non-significantly prolonged PFS and OS among men with mCRPC compared to treatment with ADT plus chemotherapy alone.