ABSTRACT
With cancer diagnosis occurring at older ages, the use of immune checkpoint inhibitors (ICIs) has extended to older adults. However, the safety of immune-related adverse events (irAEs) in this population remains unclear and relies on data extrapolated from younger adults. This multicenter retrospective study aimed to examine irAE prevalence and tolerability in older adults. We included 436 patients with non-small lung cancer undergoing ICI therapy and dichotomized them into two age groups (< or ≥75 years). Incidence of any irAE grade, grade ≥3 irAEs, and steroid usage after irAE occurrence was similar between younger (n = 332) and older groups (n = 104). While the younger patients with irAEs showed prolonged overall survival in the 12-month landmark Kaplan-Meier analysis (Hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.38-0.89, p = 0.013), the older cohort did not (HR 0.80, 95% CI 0.36-1.78, p = 0.588). Although no differences were observed with ICI continuation or re-challenge after irAE onset, the elderly cohort had double the irAE cases that required a transition to best supportive care (BSC) (11.3% vs. 22.4%, p = 0.026). In conclusion, although irAE prevalence remains consistent regardless of age, the increased conversion to BSC post-irAE onset in older adults suggests diminished tolerability and the potential absence of favorable prognosis associated with irAEs in this population.
ABSTRACT
Hypomagnesemia is a characteristic adverse event of cetuximab in patients with head and neck cancer (HNC). However, there is limited information about its prevalence, risk factors, and preventive strategies. This study aimed to investigate the risk factors of hypomagnesemia and examine the preventive effects of prophylactic magnesium (Mg) administration. We initially investigated HNC patients treated with cetuximab between 2013 and 2019. Our institute started prophylactic Mg treatment (20-mEq Mg sulfate administration before cetuximab) in practice during this period. We retrospectively assess the preventive efficacy by comparing patients before and after its implementation. In total, 109 patients were included. In 60 patients without prophylaxis, all-grade and grade ≥2 hypomagnesemia at 3 months occurred in 61.7 and 15.0% of patients. The incidence of hypomagnesemia was not affected by regimens and concomitant medications. In 49 patients treated with prophylactic Mg treatment, there was no significant decrease in the cumulative incidence of hypomagnesemia. However, the preventive Mg treatment eliminated the need for additional Mg repletion to maintain Mg levels in patients treated with paclitaxel + cetuximab. A risk factor in patients without prophylaxis was a low Mg level at pre-treatment (≤2.0 mg/dL) (odds ratio: 6.03, 95% confidence interval: 1.78-20.4, p = 0.004), whereas that in patients with prophylaxis was the number of cetuximab doses (≥10) (odds ratio: 5.50, 95% confidence interval: 1.52-19.87, p = 0.009). In conclusion, a low pre-treatment Mg level was the only risk factor that could be avoided by prophylactic Mg administration. This preventive intervention is recommended for managing cetuximab-induced hypomagnesemia.
Subject(s)
Head and Neck Neoplasms , Magnesium , Humans , Cetuximab/adverse effects , Retrospective Studies , Magnesium/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/chemically induced , Risk FactorsABSTRACT
BACKGROUND: Recent advances in immune-checkpoint inhibitors (ICIs) have highlighted the need for effective management of immune-related adverse events (irAEs). This study aimed to conduct a systematic surveillance of real-world development of irAEs for understanding their characteristics and examine the prognostic impact of steroid use for these events. METHODS: We retrospectively investigated cancer patients treated with ICIs between 2014 and 2021 and collected information about irAEs throughout their development, management, and clinical outcomes. RESULTS: Overall, 458 patients (45.4%) developed 670 irAEs. The prevalence of irAEs varied by cancer type, but it was increased in regimens with longer treatment durations. Severe irAEs were more common in the nivolumab + ipilimumab and pembrolizumab + axitinib regimens. Patients who received steroids for irAEs at a dosage of < 2 mg/kg had comparable prognosis to those who did not receive steroids; however, patients who received methylprednisolone pulse therapy, primarily for severe pneumonitis and hepatitis, had shorter overall survival than those who did not receive steroids (7.8 versus 23.4 months, p = 0.016). Furthermore, methylprednisolone pulse therapy for irAEs was a poor prognostic factor in multivariate analysis (hazard ratio: 2.19, 95% confidence interval: 1.34-2.86, p < 0.001). CONCLUSION: Steroid treatment for irAE does not affect prognosis and should thus be used promptly to control inflammation. However, pulse therapy for severe cases is a poor prognostic factor, and early detection remains the key to managing such irAEs. The irAE characteristics in each regimen should be clarified to establish and provide more sophisticated irAE management, and the current findings will be beneficial to this goal.
Subject(s)
Neoplasms , Nivolumab , Humans , Nivolumab/therapeutic use , Retrospective Studies , Neoplasms/drug therapy , Steroids , MethylprednisoloneABSTRACT
BACKGROUND: Some randomized controlled trials have evaluated the effects of low-dose computed tomography (CT) screening on lung cancer mortality in heavy smokers. Based on the results of those trials, our CT screening program recommended screening for people aged ≥40 years with a history of smoking. This retrospective study aimed to verify the validity of our CT screening program and elucidate the current state of CT screening program. METHODS: We retrospectively examined lung cancer detection in 25,189 participants who underwent chest CT screening by a mobile low-dose CT screening unit in the 10-year period from April 2009 to March 2019. Participants were recruited at Japan Agricultural Cooperatives (JA) Shimane Kouseiren. Participants requested CT screening for lung cancer. CT images were read by two pulmonologists. RESULTS: Lung cancer was identified in 82 of the 25,189 participants over 10 years, an overall lung cancer detection rate (percentage of lung cancers detected among all participants) of 0.33%. Lung cancer among never smokers accounted for 54.9% of the detected cases. The lung cancer detection rate was similar for smokers versus never smokers. The stage IA detection rate (percentage of stage IA lung cancers among all lung cancers detected) was 62%, while the stage â £ detection rate was 10%. CONCLUSIONS: Chest CT detected lung cancer in never smokers as well as current or former smokers. Our CT screening program was not effective for never smokers; thus, further study of the effectiveness of CT screening in never smokers is needed.
Subject(s)
Early Detection of Cancer , Lung Neoplasms , Adult , Humans , Japan/epidemiology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/epidemiology , Mass Screening , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
PURPOSES: Lenvatinib (LEN) is a molecular-target drug, used for unresectable hepatocellular carcinoma (HCC). It is associated with adverse events (AEs), including hypertension, proteinuria, fatigue, and anorexia, which may force dose reduction or discontinuation. Ninjin'yoeito (NYT) is a Chinese-Japanese herbal compound that can effectively treat fatigue and anorexia, and which has been used for chronic liver diseases. NYT reduces AEs and improves the liver function in patients treated with sorafenib but its effect on LEN is unclear. METHODS: The present study included 46 patients (male, n = 32; female, n = 14) who received LEN for HCC at our hospital. Their median age was 70 years (range 36-88 years), and their median body weight was 61.5 kg (range 38.4-97.0 kg). Patients were divided into two groups, depending on whether they received NYT medication. Their AEs and liver function were examined one month after starting LEN. RESULTS: The NYT group suffered less fatigue (63.6% vs. 11.4%, P = 0.0014) and showed elevated aspartate aminotransferase levels (45.5% vs. 14.3%, P = 0.0433) in comparison to the non-NYT group. The non-NYT group also showed a significantly exacerbated albumin-bilirubin (ALBI) grade (P = 0.0342) and ALBI score (average change: + 0.232, P = 0.0001) at 1 month in comparison to baseline. CONCLUSION: NYT apparently suppressed LEN-induced fatigue and helped maintain liver function in patients with HCC.
Subject(s)
Carcinoma, Hepatocellular , Drugs, Chinese Herbal/therapeutic use , Liver Neoplasms , Phenylurea Compounds/therapeutic use , Quinolines/therapeutic use , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Female , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Male , Middle Aged , Retrospective StudiesABSTRACT
Backgroundâ :â Although platinum-combination chemotherapy is widely used to treat advanced non-small cell lung cancer (NSCLC), not all elderly patients benefit from this regimen. In this retrospective study, we aimed to evaluate whether the Glasgow Prognostic Score (GPS), an indicator of systemic inflammation and malnutrition, could predict the tolerability and efficacy of platinum-combination chemotherapy among elderly patients with NSCLC. Methodsâ :â The eligibility criteria included patients aged ≥â70 years with NSCLC treated with first-line platinum-combination chemotherapy at Shimane University Hospital between January 2015 and December 2018. Resultsâ :â Thirty-two patients with NSCLC (median age, 74 years) were included. The GPS scores were 0-1 for 19 patients and 2 for 13 patients. Four chemotherapy cycles were completed by 57.9% and 30.8% of patients in the GPS 0-1 and GPS 2 groups, respectively. The GPS 0-1 group experienced better outcomes than the GPS 2 group (response rateâ :â 26% vs. 15%, Pâ=â0.67â ;â median progression-free survivalâ :â 4.1 vs. 2.1 months, Pâ=â0.0026â ;â median overall survivalâ :â 22.8 vs. 9.6 months, Pâ=â0.0092). Conclusionsâ :â Platinum-combination chemotherapy demonstrated promising efficacy among elderly NSCLC patients with a GPS 0-1. Therefore, GPS may be crucial in determining whether treatments recommended for younger patients are suitable for older patients with NSCLC. J. Med. Invest. 68 : 260-264, August, 2021.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Drug Therapy, Combination , Humans , Lung Neoplasms/drug therapy , Platinum/therapeutic use , Prognosis , Retrospective StudiesABSTRACT
The liver is an essential organ for regulating innate and acquired immunity. We hypothesized that the pre-treatment hepatic function affects the clinical outcome of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). We analyzed 140 patients with NSCLC who received ICIs. We investigated the association between pre-treatment liver function, assessed using the albumin-bilirubin (ALBI) grade, and clinical outcomes in univariate, multivariate, and propensity score matching analyses. Patients were divided into four grades according to pre-treatment liver function. Eighty-eight patients had good hepatic reserve (ALBI grade 1 or 2a), whereas 52 patients had poor hepatic reserve (ALBI grade 2b or 3). In the univariate Kaplan-Meier analysis, the ALBI grade 1, 2a group had a significantly prolonged progression-free survival (PFS, 5.3 versus 2.5 months, p = 0.0019) and overall survival (OS, 19.6 vs. 6.2 months, p = 0.0002). These results were consistent, regardless of whether the analysis was performed in patients with a performance status of 0 or 1 at pre-treatment (N = 124) or in those selected using propensity score matching (N = 76). In the multivariate analysis, pre-treatment ALBI grade was an independent prognostic factor for both PFS (hazard ratio [HR] 0.57, 95% confidence interval [95% CI] 0.38-0.86, p = 0.007) and OS (HR 0.45, 95% CI 0.29-0.72, p = 0.001). Our results suggest that pre-treatment hepatic function assessed by ALBI grade could be an essential biomarker for predicting the efficacy of treatment with ICIs in NSCLC.
Subject(s)
Bilirubin/isolation & purification , Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors/administration & dosage , Liver/drug effects , Serum Albumin, Human/isolation & purification , Adult , Aged , Aged, 80 and over , Bilirubin/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Kaplan-Meier Estimate , Liver/pathology , Liver Function Tests , Male , Middle Aged , Prognosis , Progression-Free Survival , Proportional Hazards Models , Serum Albumin, Human/genetics , Treatment OutcomeABSTRACT
BACKGROUND: The prognosis of non-small cell lung cancer (NSCLC) varies greatly depending on whether or not it can receive molecular-targeted drug treatment including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We investigated the clinical utility of C-reactive protein (CRP) levels measured at the time of diagnosis in EGFR-mutant and wild-type NSCLC patients who had undergone first-line therapy. METHODS: Serum CRP levels were analyzed in 213 patients, of whom 89 patients had advanced EGFR-mutated NSCLC who underwent first-line EGFR-TKI treatment. We used Cox proportional hazards models to study the relationship between CRP and overall survival (OS). CRP cutoff values were obtained from the receiver operating characteristic curve. RESULTS: Mean serum CRP level in treated NSCLC patients were not significantly different in patients with or without EGFR mutations. The optimal CRP cutoff values were 8.1 mg/L for EGFR-mutated NSCLC and 16.7 mg/L for EGFR-wild NSCLC. Based on multivariate analysis, high CRP level (EGFR-mutated, HR: 2.479, 95% CI: 1.331-4.619, P=0.004; EGFR-wild, HR: 3.625, 95% CI: 2.149-6.116, P<0.001) was a significant and independent negative prognostic factor for OS in patients with or without EGFR mutations. CONCLUSIONS: High CRP levels predicted a lack of response to treatment in patients with advanced lung adenocarcinoma with or without EGFR mutations. Thus, the CRP level is a good and easy to use prognostic factor and objective indicator for clinical practice.
ABSTRACT
Immune checkpoint inhibitors (ICIs) play a central role in various cancers. ICIs can cause immune-related adverse events (irAEs). As severe irAEs can be life-threatening, biomarkers for estimating irAE onset are crucial. The neutrophils-to-lymphocytes ratio (NLR) reflects the systemic immune condition and known as a prognostic marker in ICI treatment. Our study evaluated if the NLR corresponded with irAEs, and its feasibility as a biomarker for irAE onset. We retrospectively analyzed 275 cancer patients treated with anti-PD-1 monotherapy. We observed 166 irAEs in 121 patients. The NLR was significantly elevated during irAEs. Patients experiencing interstitial pneumonitis showed NLR elevation 4 weeks before initial symptoms and diagnosis. Analyzing receiver operating characteristics curves revealed that elevated NLR distinguished subsequent pneumonitis severity with high accuracy (AUC 0.93, sensitivity 88.9%, specificity 88.2%, cut-off 2.37, p = 0.0004). After a severe irAE occurred, two NLR trends were observed. Patients who showed a prompt reduction in elevated NLRs had favorable progression-free survival (hazard ratio 0.32, 95% CI 0.10-1.01, p = 0.0140) and overall survival (hazard ratio 0.23, 95% CI 0.06-0.86, p = 0.0057) compared to the patients who maintained elevated NLRs. These findings suggest that continuous monitoring of NLR trends may predict irAE onset and severity and subsequent prognosis.
Subject(s)
Biomarkers, Tumor/immunology , Immune Checkpoint Inhibitors/administration & dosage , Lymphocytes/immunology , Neoplasms/drug therapy , Neoplasms/immunology , Neutrophils/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphocytes/pathology , Male , Middle Aged , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/immunology , Neoplasms/pathology , Neutrophils/pathology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Retrospective StudiesABSTRACT
BACKGROUND: Peripheral intravenous injection of gemcitabine often causes vascular pain; however, preventive measures have not yet been established. OBJECTIVES: This study focused on identifying predictive factors for gemcitabine-induced vascular pain. METHODS: We retrospectively analyzed risk factors for developing vascular pain in patients with pancreatic cancer receiving gemcitabine infusions at our institution. Infusions were divided into groups according to presence or absence of vascular pain symptoms, and variables were compared. Odds ratios for risk factors were calculated using logistic regression analyses. RESULTS: Overall, 272 patients with pancreatic cancer were subjected to 725 gemcitabine infusions, and of these, 18.4% (n = 50) experienced vascular pain. There were significant differences in the gemcitabine dose (P = 0.025), dose of gemcitabine/body surface area (BSA; P = 0.004), concentration of gemcitabine (P = 0.025), and hot pack use (P = 0.011) between the vascular pain and no vascular pain groups. Multivariable analyses indicated that gemcitabine dose/BSA and lack of hot pack use were risk factors for developing vascular pain. Moreover, on administration of a higher dosage (>930 mg/m2), the incidence of vascular pain in patients using a hot pack (6.7%) was significantly lower than that in patients not provided a hot pack (16.2%). CONCLUSIONS AND RELEVANCE: High gemcitabine dosages and lack of hot pack use were predictive factors for gemcitabine-induced vascular pain in patients with pancreatic cancer. Patients receiving gemcitabine treatment should apply a hot pack to the injection site. Scrupulous clinical attention is required for patients presenting with these risk factors to improve pain management.
Subject(s)
Pancreatic Neoplasms , Antineoplastic Combined Chemotherapy Protocols , Deoxycytidine/analogs & derivatives , Humans , Pain/chemically induced , Pain/epidemiology , Pancreatic Neoplasms/drug therapy , Retrospective Studies , Risk Factors , GemcitabineABSTRACT
The filter extraction method is a new, simple method for evaluating anticancer drug contamination in air. The method involves installing a filter in the exhaust port of an exhaust duct on a facility's air conditioner, then collecting and measuring fine particles of the antineoplastic agents adsorbed onto the filter. In this study, we analyzed the utility of maintaining continuous filter extraction for measuring cyclophosphamide and 5-fluorouracil contamination. The filters were installed in 3 areas of an outpatient chemotherapy room and then left in place for approximately 5 months. Results revealed the presence of cyclophosphamide and 5-fluorouracil in all 3 areas. However, the amounts and ratios of detected drugs differed among survey sites; this may have been caused by factors such as drug preparation, administration, and excretion. We conclude that the filter extraction method can be used continuously for monitoring anticancer drug contamination in air; thus, it can be utilized to monitor healthcare workers' occupational exposure to inhaled anticancer drugs. Indeed, the filter extraction method may be useful as a novel environmental monitoring technique.
Subject(s)
Air Pollutants, Occupational , Antineoplastic Agents , Occupational Exposure , Air Pollutants, Occupational/analysis , Antineoplastic Agents/analysis , Cyclophosphamide , Drug Contamination , HumansABSTRACT
PURPOSE: This study aimed to examine the association between the trough plasma concentration of lenvatinib with the objective response rate (ORR) and adverse events in patients with hepatocellular carcinoma (HCC). METHODS: Twenty-one patients with HCC who received lenvatinib were enrolled. We examined the median trough concentration (Ctrough median) of plasma lenvatinib until the first clinical response evaluation. The receiver-operating characteristic curve was drawn to show the discrimination potential of the Ctrough median for the ORR, using the modified Response Evaluation Criteria in Solid Tumors. Adverse events were graded based on the Common Terminology Criteria for Adverse Events (ver. 5.0). RESULTS: The Ctrough median values in the complete response and partial response group were significantly higher than those in the stable disease and progressive disease groups. The ORR was significantly higher in the high-Ctrough median group (≥ 42.68 ng/mL) than in the low-Ctrough median group (< 42.68 ng/mL) (80.0% vs. 18.2%; p = 0.0089). Although there was no difference in the occurrence of most adverse events between the high- and low-Ctrough median groups, the occurrence of any grade anorexia (100.0% vs. 45.5%; p = 0.0124) and grade 3 serious hypertension (70.0% vs. 18.2%; p = 0.0300) was significantly higher in the high-Ctrough median group than in the low-Ctrough median group. Multivariate analysis showed that high-Ctrough median was significantly associated with ORR development (odds ratio, 15.00; 95% confidence interval, 1.63-138.16; p = 0.0168). CONCLUSION: Maintaining Ctrough median above 42.68 ng/mL was crucial for achieving the ORR in patients with HCC.
Subject(s)
Carcinoma, Hepatocellular/drug therapy , Drug Monitoring/methods , Liver Neoplasms/drug therapy , Phenylurea Compounds/pharmacokinetics , Protein Kinase Inhibitors/pharmacokinetics , Quinolines/pharmacokinetics , Administration, Oral , Aged , Aged, 80 and over , Anorexia/chemically induced , Anorexia/diagnosis , Anorexia/epidemiology , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/pathology , Disease Progression , Female , Humans , Hypertension/chemically induced , Hypertension/diagnosis , Hypertension/epidemiology , Liver/diagnostic imaging , Liver/drug effects , Liver/pathology , Liver Neoplasms/blood , Liver Neoplasms/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Phenylurea Compounds/administration & dosage , Phenylurea Compounds/adverse effects , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Quinolines/administration & dosage , Quinolines/adverse effects , ROC Curve , Response Evaluation Criteria in Solid Tumors , Severity of Illness Index , Tomography, X-Ray ComputedABSTRACT
OBJECTIVES: To examine the possible effects of antinuclear antibodies (ANA) on the safety and efficacy of programmed cell death-1 (PD-1) inhibitors in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Clinical data including ANA status were reviewed retrospectively for patients with advanced NSCLC who received monotherapy with a PD-1 inhibitor. RESULTS: Of the 83 patients analyzed, 18 (21.7%) were positive for ANA. The incidence of immune-related adverse events (irAEs) did not differ significantly between patients with ANA (6/18, 33.3%) and those negative for ANA (21/65, 32.3%), although it tended to increase as the ANA titer increased. Progression-free survival (2.9 versus 3.8 months, p = 0.03) and overall survival (11.6 versus 15.8 months, p = 0.03) were significantly shorter in patients positive for ANA than in those without ANA. CONCLUSION: PD-1 inhibitors can be administered safely in advanced NSCLC patients positive for ANA without obvious exacerbation of autoimmune disease, although patients with a high titer of such antibodies may warrant close monitoring. However, the presence of ANA might be associated with a poor outcome of such treatment.
Subject(s)
Antibodies, Antinuclear/blood , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Autoimmune Diseases/epidemiology , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/mortality , Cohort Studies , Female , Humans , Incidence , Japan/epidemiology , Lung Neoplasms/epidemiology , Lung Neoplasms/mortality , Male , Middle Aged , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: Antiemetic effects and safety of granisetron or palonosetron alone and in combination with a corticosteroid against chemotherapy-induced nausea and vomiting (CINV) were retrospectively evaluated in patients with Hodgkin lymphoma receiving adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) therapy. METHODS: A total of 39 patients were eligible for this study. Before ABVD therapy, granisetron or palonosetron was intravenously administered with or without a corticosteroid (dexamethasone or hydrocortisone) and aprepitant. The proportions of patients with complete control (CC) during the overall (0-120 h after the start of ABVD therapy), acute (0-24 h) and delayed (24-120 h) phases were evaluated. CC was defined as no vomiting and no use of antiemetic rescue medication with only grade 0-1 nausea. RESULTS: Granisetron and palonosetron were administered in 21 and 18 patients, respectively. The CC rate during the acute, delayed and overall phases was not statistically different between the two groups. The CINV was completely controlled during overall phase in 58.3% of patients receiving granisetron or palonosetron in combination with a corticosteroid, whereas in 11.1% of those without co-treatment of a corticosteroid (P < 0.05). There were significantly higher frequencies of anorexia, leucopenia and neutropenia in the palonosetron group. There is a statistically significant difference in the frequency of febrile neutropenia between presence and absence of a corticosteroid (p = 0.024). CONCLUSION: These findings suggested that a combination use of a corticosteroid with a 5-HT3 receptor antagonist was preferable for CINV control in patients with Hodgkin lymphoma receiving ABVD therapy, although the careful management of febrile neutropenia is required. TRIAL REGISTRATION: The study approval numbers in the institution; 24-12 and 24-359. Registered April 17, 2012 and June 21, 2012.
ABSTRACT
Capecitabine, an oral prodrug of 5-fluorouracil (5-FU), is a promising treatment for colorectal, breast and gastric cancers, but often causes hand-foot syndrome (HFS), the most common dose-limiting toxicity. The current study was conducted to investigate the relationship between HFS and efficacy of capecitabine in 98 patients with metastatic breast cancer. Possible associations between HFS and efficacy endpoints, including time-to-treatment failure (TTF), tumor response in metastatic lesions and changes in tumor markers, were investigated retrospectively using electronic medical records. The TTF of group with HFS of grade 1 and ≥2 was significantly longer than that of group with no HFS, respectively (hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.18-0.87 for group with grade 1; HR, 0.42, 95% CI, 0.19-0.90 for group with grade ≥2). Significantly higher disease control rates for the liver metastasis were observed in patients with HFS (grade 1 and greater) than in those without HFS (92.9 vs. 42.9%, p=0.009). Furthermore, prevention of increases in tumor marker levels (carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3) and National Cancer Center-Stomach-439 (NCC-ST439)) was evident in patients with HFS. This study clearly showed a significant correlation between HFS and some efficacy markers of capecitabine therapy in patients with metastatic breast cancer, and suggests that early dose adjustment based on severity of HFS might improve efficacy. Studies are needed to explore predictive biomarkers for HFS/efficacy, so that capecitabine therapy can be further tailored to patient response.
Subject(s)
Antimetabolites, Antineoplastic/adverse effects , Breast Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Hand-Foot Syndrome/etiology , Liver Neoplasms/drug therapy , Aged , Antimetabolites, Antineoplastic/therapeutic use , Biomarkers, Tumor/blood , Breast Neoplasms/blood , Breast Neoplasms/pathology , Capecitabine , Confidence Intervals , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Female , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Humans , Liver Neoplasms/blood , Liver Neoplasms/secondary , Middle Aged , Prodrugs/adverse effects , Prodrugs/therapeutic use , Proportional Hazards Models , Retrospective Studies , Treatment OutcomeABSTRACT
Clinical background and incidence of hepatocellular carcinoma (HCC) of patients with chronic hepatitis C who obtained biochemical remission without eradication of virus (biochemical response) after interferon (IFN) treatment was retrospectively analyzed for 755 patients. Annual incidence of HCC was significantly lower in the patients with biochemical response and sustained response than that of the patients that did not show these responses. Logistic regression analysis showed that only the normalization of alanine aminotransferase (ALT) value at the end of IFN treatment was a significant factor for biochemical response. Annual incidence of HCC was significantly lower in the patients who obtained normalization of ALT values at the end of treatment than those who did not. Patients who were younger, who had a lower level of activity and fibrosis indices in histology, higher platelet count, and who were given more higher total dose of IFN were more likely to attain normalization of ALT levels at the end of treatment, and this was related to biochemical response. Low incidence of HCC in patients who obtained normalization of ALT values at the end of treatment was likely because they were in the earlier stage of chronic hepatitis. Active treatment of chronic hepatitis C with interferon in the early phase of the disease may bring about a biochemical response in some patients, even if sustained virological response is not obtained.
Subject(s)
Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/epidemiology , Hepatitis C, Chronic/drug therapy , Interferons/therapeutic use , Liver Neoplasms/epidemiology , Adult , Alanine Transaminase/blood , Carcinoma, Hepatocellular/prevention & control , Carcinoma, Hepatocellular/virology , Cell Transformation, Neoplastic , Female , Hepacivirus/isolation & purification , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/complications , Humans , Incidence , Liver Neoplasms/prevention & control , Liver Neoplasms/virology , Male , Middle Aged , Remission Induction , Retrospective StudiesABSTRACT
A retrospective multicenter analysis of 652 patients with chronic hepatitis C who have been treated with interferon (IFN) was performed to assess the effects of IFN on the clinical course and development of HCC. During a mean follow-up of 54.8 months, hepatocellular carcinoma (HCC) developed in 7.0% of the patients. The rate was significantly higher in the patients who did not respond to IFN treatment than in those with sustained virological response and those who obtained a normalization of alanine aminotransferase levels despite the presence of HCV RNA (incomplete response) (P < 0.01). Using multivariate Cox's proportional hazard model, alcohol abuse (P < 0.05) and a higher level of fibrosis (P < 0.05) before treatment were the significant background factors associated with HCC development in the patients who did not respond to IFN. Interestingly, a significant increase in the rate of HCC development occurred in patients who had a histological finding of progressive fibrosis (F3). In addition, patients with low histological staging scores were likely to have an incomplete response, even if a sustained virological response was not obtained. IFN produced an improvement in histological activity and fibrosis stage in the second biopsy specimens irrespective of the clinical outcome when compared against untreated subjects.