Tolerability Of Chemotherapy In Patients Research Articles

Effects of intermittent fasting on quality of life tolerance of chemotherapy in patients with gynecological cancers: study protocol of a randomized-controlled multi-center trial.

https://drks.de, identifier DRKS00031429.

Tumour extracellular vesicles and particles induce liver metabolic dysfunction.

Cancer alters the function of multiple organs beyond those targeted by metastasis1,2. Here we show that inflammation, fatty liver and dysregulated metabolism are hallmarks of systemically affected livers in mouse models and in patients with extrahepatic metastasis. We identified tumour-derived extracellular vesicles and particles (EVPs) as crucial mediators of cancer-induced hepatic reprogramming, which could be reversed by reducing tumour EVP secretion via depletion of Rab27a. All EVP subpopulations, exosomes and principally exomeres, could dysregulate hepatic function. The fatty acid cargo of tumour EVPs-particularly palmitic acid-induced secretion of tumour necrosis factor (TNF) by Kupffer cells, generating a pro-inflammatory microenvironment, suppressing fatty acid metabolism and oxidative phosphorylation, and promoting fatty liver formation. Notably, Kupffer cell ablation or TNF blockade markedly decreased tumour-induced fatty liver generation. Tumour implantation or pre-treatment with tumour EVPs diminished cytochrome P450 gene expression and attenuated drug metabolism in a TNF-dependent manner. We also observed fatty liver and decreased cytochrome P450 expression at diagnosis in tumour-free livers of patients with pancreatic cancer who later developed extrahepatic metastasis, highlighting the clinical relevance of our findings. Notably, tumour EVP education enhanced side effects of chemotherapy, including bone marrow suppression and cardiotoxicity, suggesting that metabolic reprogramming of theliver by tumour-derived EVPs may limit chemotherapy tolerance in patients with cancer. Our results reveal how tumour-derived EVPs dysregulate hepatic function and their targetable potential, alongside TNF inhibition, for preventing fatty liver formation and enhancing the efficacy of chemotherapy.

Video-assisted thoracic surgery is associated with faster delivery to adjuvant chemotherapy after lung resection in patients with lung cancer

BackgroundRapid recovery after surgery is especially important for patients who are scheduled for adjuvant therapy.This study aimed to investigate the effect of video-assisted thoracic surgery (VATS) on chemotherapy referral time and chemotherapy tolerance in patients who underwent lung resection for non-small cell lung cancer.MethodsThe data of 612 patients who underwent lung resection with the diagnosis of non-small cell lung cancer in our clinic between January 2014 and December 2021 were reviewed. Patients who underwent lobectomy or bilobectomy with systematic mediastinal lymph node dissection and who received at least one cycle of adjuvant chemotherapy were included in the study. The characteristics of the patients, pathological data, postoperative follow-up findings, and the time between the operation and adjuvant chemotherapy were recorded.ResultsA total of 144 patients who met the criteria were included in the study. The mean age was 61.6 ± 7.9 years. The mean visual analogue scale scores were found to be lower, and the length of hospital stay was found to be shorter in the VATS group compared to thoracotomy.The mean time (days) to initiate chemotherapy after surgery was statistically shorter in the VATS group (48.9 ± 17.6 vs 58.1 ± 27.6, p = 0.049). However, there weren't seen any statistical differences between VATS and thoracotomy groups in terms of mean cycle completed, percentage of planned regimen received, and grade ≥ 3 toxicity rates (p = 0.16, p = 0.18, and p = 0.22, respectively).ConclusionsVATS provides faster recovery compared to open surgery and shortens the time for patients to refer to adjuvant chemotherapy.

Sarcopenia detected with bioelectrical impedance versus CT scan and chemotherapy tolerance in patients with early breast cancer.

Early breast cancer (EBC) is a potentially curable disease. Some patients with EBC require chemotherapy, exposing patients to undesirable side effects. Loss of muscle mass, or sarcopenia, has been associated with worse outcomes in patients with EBC and worse treatment-related toxicity in patients with advanced breast cancer. CT scans can identify sarcopenia; however, most patients with EBC do not require routine CT scans. Bioelectrical impedance spectrometry (BIS) is another method to detect sarcopenia and can be performed quickly in the office without radiation exposure. We sought to investigate whether sarcopenia measurements by CT scan versus BIS correlated with each other and whether sarcopenia identified by each method is associated with chemotherapy toxicity and adherence in patients with EBC. This is a retrospective study; eligible patients received chemotherapy treatment for EBC and had undergone BIS. A subset of patients had also had a CT abdomen with a Lumbar L3 level. Measures of sarcopenia were obtained from the BIS and CT data. In addition, patient characteristics, treatment, and toxicity-related outcomes were obtained from medical records. Multivariate logistic regression models were used to associate sarcopenia status with toxicity endpoints, adjusted for other patient characteristics. There was a moderate correlation between sarcopenia detected by CT scan and BIS (r = 0.64 p < 0.0001). Patients with sarcopenia detected by BIS had more chemotherapy toxicity (OR = 2.56; CI 1.72-3.84), dose reductions or dose delays (OR = 1.58; CI 1.06-2.38), and hospitalizations (OR = 2.38; CI 1.33-4.16) due to side effects than patients without sarcopenia. The presence of sarcopenia in patients with EBC is associated with worse chemotherapy tolerance. BIS represents a high-value alternative to CT scans for sarcopenia assessment.

Short-term outcomes of preoperative chemotherapy in patients with upper ampullary rectal cancer

The purpose of the study: to analyze short-term efficacy and tolerability of preoperative chemotherapy in patients with upper ampullary rectal carcinoma. Material and methods. A prospective study conducted at the cancer research institute (tomsk, russia) between 2018 and 2020 included 47 patients with operable cancer of the upper ampullary part of the rectum with mrt3n0m0 (mesorectal fascia involvement (crm+) or low-grade cancer), mrt4аn0m0 and mrt3–4аn1m0. All patients were divided into two groups. Group i comprised 22 patients, who received 3 cycles of chemotherapy with folfox-4 followed by surgery. Group ii consisted of 25 patients, who underwent surgery alone. All patients underwent arterior resection of the rectum. Results. Group i patients completed all three cycles of preoperative chemotherapy. Downstaging after chemotherapy was observed in 16 (72.7 %) patients. No severe side effects of chemotherapy were found. The frequency of radical surgeries (r0) was 100 %. No significant differences in the rate of postoperative complications between the treatment groups were observed (18.2 % and 16 %, respectively, p&gt;0.05). There were no cases of postoperative mortality. Conclusion. Compared with surgery alone, preoperative chemotherapy followed by surgery demonstrates a high short-term efficacy, does not adversely affect the course of the perioperative period.

Physical Fitness and Chemotherapy Tolerance in Patients with Early-Stage Breast Cancer.

ABSTRACTIntroductionAn optimal relative dose intensity (RDI) of adjuvant chemotherapy is associated with better survival in patients with breast cancer. Little is known about the role of physical fitness in attaining an adequate RDI in patients with early-stage breast cancer. We investigated the association between pretreatment physical fitness and RDI in this population.MethodsWe pooled individual patient data from two randomized exercise trials that studied exercise programs in early breast cancer: the Physical Exercise During Adjuvant Chemotherapy Effectiveness Study (n = 230) and the Physical Activity during Chemotherapy Treatment (n = 204) study. Logistic regression models were used to evaluate the association between pretreatment fitness and achieving an optimal RDI (≥85%). In addition, we added an interaction term to the model to explore the potential moderating effect of participating in an exercise program.ResultsData were available for 419 patients (mean age at diagnosis, 50.0 ± 8.6 yr). In the total sample, lower pretreatment physical fitness was associated with significantly lower odds of achieving ≥85% RDI: age-adjusted odds ratio (OR) of 0.66 (95% confidence interval (CI), 0.46–0.94). In patients allocated to the supervised exercise intervention during chemotherapy (n = 173), the association between pretreatment physical fitness and RDI was almost completely mitigated (OR, 0.95 (95% CI, 0.54–1.56)), whereas it was more pronounced in patients who received care as usual (n = 172; OR, 0.31 (95% CI, 0.13–0.63); Pinteraction = 0.022).ConclusionsEarly-stage breast cancer patients with relatively lower levels of pretreatment physical fitness have lower odds of achieving an optimal dose of chemotherapy. Given that physical fitness is modifiable and our results suggest that following a moderate-to-high intensity exercise training during chemotherapy could improve treatment completion, clinicians should not refrain from referring patients to supportive exercise programs because of low fitness.

Pharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis

Aim. To assess the association between the carriage of minor allelic variants of 8 genes that encode key enzymes involved in the metabolism of anticancer drugs (DPYD, GSTP1, MTHFR, UGT1A1) and cell repair (XPC, ERCC1, TYMP, NQO1) and the severity of adverse drug events in patients with common gastrointestinal tumors. Tasks. To study the frequency of minor allelic variants of the DPYD, GSTP1, MTHFR, UGT1A1, XPC, ERCC1, TYMP, NQO1 genes; to assess the frequency and severity of adverse drug events of chemotherapy treatment in the study population. Materials and methods. For the period from October 2020 to April 2021, 56 patients (women 29, men 27) with verified malignant tumors of the gastrointestinal tract were included in a prospective clinical study as a part of the RSF grant No. 20-75-10158. The mean age was 62.311.4 years. Colon cancer was detected in 24 patients, tumors of the esophagus and stomach in 19 patients, tumors of pancreas and biliary tract in 13 patients. First-line palliative chemotherapy was given to 27 patients, adjuvant 19 patients, neoadjuvant 10 patients. All patients had not previously received cytotoxic or radiation treatment. Point nucleotide variants of genes DPYD, XPC, GSTP1, MTHFR, ERCC1, UGT1A1, TYMPS, NQO1 were determined by hybridization analysis on biological microchips. Differences in the tolerance of cytotoxic therapy (5-fluorouracil, platinum preparations, irinotecan) depending on the genotype were assessed using Fishers exact test. Results. The average number of chemotherapy courses received was 4.22.6 (112). There was a statistically significant difference in the tolerability of chemotherapy in patients with minor allelic variants of the GSTP1 rs1695 (p=0.03), ERCC1 rs11615 (p=0.01), and UGT1A1 rs8175347 (p=0.003) genes. Conclusion. The use of hybridization analysis on biological microchips to assess allelic variants responsible for the tolerability of cytotoxic therapy is reasonable and requires further prospective assessment.

Cancer Incidence and Chemotherapy Tolerance in Patients with Sickle Cell Disease

With improved understanding and treatment of sickle cell disease (SCD), patients are more likely to live into the sixth decade. Survival into older adulthood may be associated with a concomitant risk of malignancy in this population. Past studies have yielded conflicting data regarding the incidence of cancer in SCD. Some studies show an increased risk of hematologic malignancies or solid tumors, while others demonstrate a decreased propensity for cancers in patients with SCD. Delays in treatment and dose reductions can adversely affect response and survival outcomes, but little is known about the ability of SCD patients to tolerate treatment for various malignancies. We studied the incidence of cancer and tolerance of chemotherapy over a 10-year-period at the University of Illinois at Chicago in a retrospective chart review. Our study included 1484 SCD patients of all ages seen at our institution from September 30, 2010 to April 29, 2020. The patient records were queried for common malignancies using ICD-9 and ICD-10 codes, including colorectal, lung, breast, prostate, renal, and cervical cancer as well as lymphoma, leukemia, and multiple myeloma. These cases were verified by manual chart review (Figure 1A). The incidence of cancer was compared to an African American (AA) control cohort of 22,260 patients matched for age, sex, and follow-up time. For patients who received chemotherapy, details on regimen and tolerability were obtained. Baseline variables were defined as the median of all available values three years prior to treatment. Dose limiting toxicities (DLT) were defined as any reason for which an expected dose could not be administered. Of the 1484 SCD patients, 48 (3.2%) had a cancer diagnosis according to ICD codes. Among the AA control population, 1282/22260 (5.8%) had cancer according to ICD codes. The incidence of common malignancies was significantly decreased in the SCD population (OR 0.55, p&amp;lt;0.001, 95% CI 0.40 to 0.73). Of the 48 SCD cancer cases, we were able to confirm 19 (39.6%) by manual chart review and 16 of these patients were diagnosed during the study period. Characteristics of the 16 SCD cancer patients are summarized in Table 1 and distribution of cancer types is shown in Figure 1B. Eight (50%) of these patients were known to receive chemotherapy, and treatment details are shown in Table 2. First-line treatment was not given in 2 (25%) cases due to comorbidities such as SCD, poor functional status, toxicity, age, and renal insufficiency. Grade 3 or 4 toxicities took place in 5 (62.5%) patients, including anemia, neutropenia, leukopenia, thrombocytopenia, dehydration, nausea and or vomiting, and hemorrhagic cystitis. Six (75%) patients had a vaso-occlusive crisis (VOC) and 1 (12.5%) had an acute chest syndrome episode during therapy. DLT in 4 (50%) patients included nephrotoxicity, infection, pain, and hepatotoxicity. Four (50%) patients did not receive all scheduled cycles for reasons including concern for cerebrovascular accident (CVA), fatigue, anorexia, dehydration, VOC, infection, and progression of disease. Two (25%) patients required change in chemotherapy regimen due to toxicity. Our study raises several questions regarding both the incidence and treatment of cancer in SCD. There was a significantly lower incidence of cancer among SCD patients compared to AA controls. Mechanisms by which SCD patients may be protected from cancer are unknown, but should be explored in future studies. Patients who received chemotherapy in our study experienced significant toxicities, delays, and dose reductions. Such issues were often SCD-related or due to other typical hematologic toxicities. Although the goal for treating SCD cancer patients may be with therapies that result in outcomes similar to the general population, our data suggests that this is difficult with routine protocols. Increased monitoring and a multimodal approach to symptom control may increase treatment tolerability and ensure adequate dose delivery. Evidence of poor chemotherapy tolerance in SCD patients highlights the need for further and larger studies to determine treatment strategies for this population. Disclosures Saraf: Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Boards, Speakers Bureau; Novartis, Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer, Global Blood Therapeutics, Novartis: Research Funding. Gordeuk:Novartis: Consultancy; CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Imara: Research Funding; Ironwood: Research Funding.

Should calculation of chemotherapy dosage for bowel cancer be based on body composition?

Dosage of chemotherapy for colon cancer is currently based on the patient's body surface area. Several studies have identified an association between low fat-free mass and chemotherapy toxicity among patients with metastatic colorectal cancer. This has been less widely studied for localised disease. This review aims to summarise studies that have investigated the association between clinical signs of disease-related malnutrition (low body mass index, weight loss and low muscle mass) and tolerance of chemotherapy in patients with localised colon cancer. We conducted a systematic search in PubMed with various synonyms of the terms 'colorectal cancer', 'adjuvant chemotherapy', 'nutritional status' and 'toxicity'. The search was concluded in May 2019. Of 553 articles, 39 were considered relevant and read in full text. Ten of these fulfilled the inclusion criteria for this review. Nine of the ten studies indicate an association between clinical signs of disease-related malnutrition and dose-limiting toxicity. The association appears to be especially pronounced in patients with low fat-free mass. The results support the hypothesis that there is an association between disease-related malnutrition and the prevalence of toxicity and modification of the course of adjuvant chemotherapy in patients with localised colon cancer. The potential benefits of basing chemotherapy dosage on body composition in addition to body surface area should be investigated in clinical trials.

670P - Impact of primary tumour resection on survival and chemotherapy tolerance in patients with metastatic oesophagogastric cancer undergoing palliative chemotherapy

670P - Impact of primary tumour resection on survival and chemotherapy tolerance in patients with metastatic oesophagogastric cancer undergoing palliative chemotherapy

Efficacy and tolerance of pegaspargase-based chemotherapy in patients with nasal-type extranodal NK/T-cell lymphoma: a pilot study.

Nasal-type extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a highly invasive cancer with a poor prognosis. More effective and safer treatment regimens for ENKL are needed. Pegaspargase (PEG-Asp) has a similar mechanism of action to L-asparaginase (L-Asp), but presents lower antigenicity. The aim of the present research was to evaluate the safety profile and the latent efficacy of a PEG-Asp-based treatment regimen in patients with ENKL. Data collected from 20 patients with histologically confirmed ENKL, admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to August 2013, were included in the study. All patients received 2500 IU/m2/IM PEG-Asp on day 1 of every 21-day treatment cycle. Patients received combination chemotherapy with CHOP (n=5), EPOCH (n=7), GEMOX (n=7) or CHOP with bleomycin (n=1). After 2-5 treatment cycles (median, 4 cycles) of PEG-Asp-based chemotherapy, five patients (25%) showed a complete response (CR), and the overall response rate (ORR) was 60%. Grade 3/4 neutropenia occurred in fourteen patients (70%). Grade 3 alanine aminotransferase (ALT) elevation was observed in two. Grade 1-2 non-hematological toxicity consisted of activated partial thromboplastin time (APTT) elongation (n=9), hypofibrinogenemia (n=6), hypoproteinemia (n=17), hyperglycemia (n=3), and nausea (n=6). No allergic reactions were detected. No treatment related death was reported. Our results suggested that PEG-Asp-based chemotherapy presented an acceptable tolerance and a potential short-term outcome in patients with nasal-type ENKL.

Metronomic chemotherapy as a palliative treatment in poor performance status patients with advanced epithelial ovarian carcinoma

Objective The aim of our study was to evaluate the clinical efficacy and tolerability of metronomic chemotherapy in patients with advanced ovarian carcinoma.

Chemotherapy in Advanced Gastric Cancer: A Systematic Review and Meta-Analysis Based on Aggregate Data

This systematic review and meta-analysis were performed to assess the efficacy and tolerability of chemotherapy in patients with advanced gastric cancer. Randomized phase II and III clinical trials on first-line chemotherapy in advanced gastric cancer were identified by electronic searches of Medline, Embase, the Cochrane Controlled Trials Register, and Cancerlit; hand searches of relevant abstract books and reference lists; and contact to experts. Meta-analysis was performed using the fixed-effect model. Overall survival, reported as hazard ratio (HR) with 95% CI, was the primary outcome measure. Analysis of chemotherapy versus best supportive care (HR = 0.39; 95% CI, 0.28 to 0.52) and combination versus single agent, mainly fluorouracil (FU) -based chemotherapy (HR = 0.83; 95% CI = 0.74 to 0.93) showed significant overall survival benefits in favor of chemotherapy and combination chemotherapy, respectively. In addition, comparisons of FU/cisplatin-containing regimens with versus without anthracyclines (HR = 0.77; 95% CI, 0.62 to 0.95) and FU/anthracycline-containing combinations with versus without cisplatin (HR = 0.83; 95% CI, 0.76 to 0.91) both demonstrated a significant survival benefit for the three-drug combination. Comparing irinotecan-containing versus nonirinotecan-containing combinations (mainly FU/cisplatin) resulted in a nonsignificant survival benefit in favor of the irinotecan-containing regimens (HR = 0.88; 95% CI, 0.73 to 1.06), but they have never been compared against a three-drug combination. Best survival results are achieved with three-drug regimens containing FU, an anthracycline, and cisplatin. Among these, regimens including FU as bolus exhibit a higher rate of toxic deaths than regimens using a continuous infusion of FU, such as epirubicin, cisplatin, and continuous-infusion FU.