First-cycle Chemotherapy Research Articles

Delayed addition of PD-1/PD-L1 inhibitors into chemotherapy on the outcomes for patients with extensive-stage small cell lung cancer: A propensity score-matched study.

208 Background: Immunotherapy in combination with chemotherapy has become the first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, some patients failed to undergo simultaneous immunotherapy at the time of initial chemotherapy, and whether this will have an impact on the efficacy of immunochemotherapy has not been fully explored. Methods: Between January 2020 and December 2022, the study included 416 patients diagnosed with ES-SCLC and receiving first-line immunotherapy, divided into two groups: delayed-IO (administering PD-1/PD-L1 inhibitors at 2-4 Cycles of chemotherapy) and early-IO (administering PD-1/PD-L1 inhibitors concurrent with first-cycle chemotherapy). Propensity score matching (PSM, 1:1) was performed to balance the baseline characteristics of the two groups. The primary endpoints were OS and PFS. Calculations were performed using the Kaplan-Meier method and comparisons were made using the log-rank test. Results: Mainly due to the fact that PD-L1/PD-1 inhibitors were not included in the medical insurance, which was difficult for patients to afford and the poor physical condition of some patients, taking into account the safety of the patients themselves, 72 patients in the delayed-IO group (2 cycles of chemotherapy: 41; 3 cycles: 16; 4 cycles: 15), and 344patients were included in the early-IO group. The median OS and PFS were 24.00 months and 8.75 months in the delayed-IO group, and those were 18.59 months and 7.57 months in the early-IO group, respectively, before PSM. There was no significant difference in OS and PFS between the two groups (HR 0.72; P = 0.054 and HR 0.86; P = 0.281, respectively). After PSM, there were 72 patients in each of the two groups. The median OS in the delayed-IO group and the early-IO group was 24.00 months and 18.79 months, respectively (HR 0.60, 95% CI 0.38-0.97; P = 0.037). Median PFS was 8.75 and 6.49 months in the two groups, respectively (HR 0.69, 95% CI 0.48-0.99; P = 0.044). There was a statistically significant difference between the two groups. The overall adverse event profile was comparable between the two groups. Conclusions: Our findings suggest that administering PD-1/PD-L1 inhibitors at 2-4 Cycles of chemotherapy was superior to administering PD-1/PD-L1 inhibitors concurrent with first-cycle chemotherapy in patients with ES-SCLC, while the safety profile of both was similar.

The reliability of FEbrile Neutropenia after ChEmotherapy (FENCE) scores in predicting granulocyte colony-stimulating factor breakthrough febrile neutropenia among patients with lymphoma undergoing first-cycle chemotherapy: A prospective observational study.

A tool for estimating risk of febrile neutropenia (FN) after chemotherapy, namely the FEbrile Neutropenia after ChEmotherapy (FENCE) score, has been developed but has not been widely validated. This study aimed to validate the FENCE score as a tool for predicting granulocyte colony-stimulating factor (G-CSF) breakthrough FN among patients with lymphoma who underwent chemotherapy. This was a prospective observational study of treatment-naive adult patients with lymphoma who underwent their first cycle of chemotherapy between 2020 and 2021. The patients were followed up until the next cycle of chemotherapy to identify any infection events. Among the 135 patients with lymphoma, 62 (50%) were men. In a comparison of the value of each FENCE parameter for predicting G-CSF breakthrough infection, the parameter of advanced-stage disease showed high sensitivity of 92.8%, and receipt of platinum chemotherapy showed high specificity of 95.33%. With a FENCE score of 12 as a cutoff for low risk, analysis across all patients with lymphoma resulted in a high AUROCC of 0.63 (95% CI = 0.5-0.74%; p = 0.059), and analysis across only patients with diffuse large B-cell lymphoma (DLBCL) resulted in an AUROCC of 0.65 (95% CI = 0.51-0.79%; p = 0.046). With a cutoff point of 12, FENCE score can predict breakthrough infection events at 30.0% (95% CI = 17.8-47.4%). This study divided patients with lymphoma into risk groups according to FENCE score, showing that this instrument has discriminatory ability in predicting FN events, these being more likely to occur in patients in the intermediate- and high-risk groups. Multicenter studies are needed to validate this clinical risk score.

Validation of the FENCE Risk Groups for Prediction of Febrile Neutropenia With First-Cycle Chemotherapy.

BackgroundThe FEbrile Neutropenia after ChEmotherapy (FENCE) score was developed to estimate the risk of febrile neutropenia (FN) at first cycle of chemotherapy but has not been externally validated. We aimed to validate the FENCE score based on its risk groups in patients treated at a comprehensive cancer center.MethodsWe conducted a retrospective study of treatment-naïve adult patients with solid tumors and diffuse large B-cell lymphoma who received first-cycle chemotherapy between January and November 2019. Patients were followed until the second cycle of chemotherapy to identify any FN events (neutrophil count <0.5 × 109/L with fever ≥38.2°C). The FENCE score was determined and patients classified as low, intermediate, high, and very high risk. The discriminatory ability of classifying patients into FENCE risk groups was calculated as the area under the receiver operating characteristics curve and incidence rate ratios within each FENCE risk group.ResultsFN was documented during the first cycle of chemotherapy in 45 of the 918 patients included (5%). The area under the receiver operating characteristics curve was 0.66 (95% confidence interval [CI] = 0.58 to 0.73). Compared with the low-risk group (n = 285), the incidence rate ratio of developing FN was 1.58 (95% CI = 0.54 to 5.21), 3.16 (95% CI = 1.09 to 10.25), and 3.93 (95% CI = 1.46 to 12.27) in the intermediate (n = 293), high (n = 162), and very high (n = 178) risk groups, respectively.ConclusionsIn this study, classifying patients into FENCE risk groups demonstrated moderate discriminatory ability for predicting FN. Further validation in multicenter studies is necessary to determine its generalizability.

BBCIC Research Network Analysis of First-Cycle Prophylactic G-CSF Use in Patients Treated With High-Neutropenia Risk Chemotherapy.

Chemotherapy-induced febrile neutropenia (FN) is prevented or minimized with granulocyte colony-stimulating factors (G-CSFs). Several G-CSF biosimilars are approved in the United States. The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) is a nonprofit initiative whose objective is to provide scientific evidence on real-world use and comparative safety and effectiveness of biologics and biosimilars using the BBCIC distributed research network (DRN). We describe real-world G-CSF use in patients with breast or lung cancer receiving first-cycle chemotherapy associated with high FN risk. We assessed hospitalizations for FN, availability of absolute neutrophil counts, and G-CSF-induced adverse events to inform future observational comparative effectiveness studies of G-CSF reference products and their biosimilars. A descriptive analysis of 5 participating national health insurance plans was conducted within the BBCIC DRN. A total of 57,725 patients who received at least one G-CSF dose were included. Most (92.5%) patients received pegfilgrastim. FN hospitalization rates were evaluated by narrow (<0.5%), intermediate (1.91%), and broad (2.99%) definitions. Anaphylaxis and hyperleukocytosis were identified in 1.15% and 2.28% of patients, respectively. This analysis provides real-world evidence extracted from a large, readily available database of diverse patients, characterizing G-CSF reference product use to inform the feasibility of future observational comparative safety and effectiveness analyses of G-CSF biosimilars. We showed that the rates of FN and adverse events in our research network are consistent with those reported by previous small studies. Readily available BBCIC DRN data can be used to assess G-CSF use with the incidence of FN hospitalizations. Insufficient laboratory result data were available to report absolute neutrophil counts; however, other safety data are available for assessment that provide valuable baseline data regarding the effectiveness and safety of G-CSFs in preparation for comparative effectiveness studies of reference G-CSFs and their biosimilars.

37P Correlation between haematological toxicity with quality of life in breast cancer patients after first-cycle chemotherapy

37P Correlation between haematological toxicity with quality of life in breast cancer patients after first-cycle chemotherapy

Quality of Life Among Breast and Colon Cancer Patients Before and After First-Cycle Chemotherapy.

This study aimed to compare the functioning, symptoms, and quality of life (QoL) of patients with breast or colon cancer before and after their first-cycle (FC) chemotherapy. One-group pretest/posttest design. The study utilized the standardized Arabic-translated Quality of Life Questionnaire Version 3 from the European Organization for Research and Treatment of Cancer in measuring the functioning, symptoms, and QoL of 120 Saudi patients diagnosed with breast or colon cancer. Dependent t test was used in analyzing the presence of significant differences in mean scores before and after chemotherapy with periods ranging from 14 days to 21 days following the treatment protocol. The findings revealed significant differences in the functioning, symptoms, and QoL among patients with breast or colon cancer before and after FC chemotherapy (p < .001). Baseline scores showed higher physical, role, emotional, cognitive, and social functioning; lesser symptoms; lower financial difficulties; and better overall global health status compared to post-FC chemotherapy. Assessing the QoL of patients with breast or colon cancer undergoing FC chemotherapy is essential to establish a holistic care plan in supporting and alleviating the unfavorable effects of chemotherapy and implement patient-centered interventions that aid in the enhancement of their overall QoL.

Effectiveness of Yoga on Quality of Life of Breast Cancer Patients Undergoing Chemotherapy: A Randomized Clinical Controlled Study.

Background:Cancer of breast is most common cancer among women in India and vast majority of countries worldwide. While undergoing chemotherapy for carcinoma management, women encounter side effects, which affects their quality of life (QOL). A randomized controlled study with quantitative research approach and time series design was conducted, to study the effectiveness of yoga on QOL of breast cancer patients undergoing chemotherapy.Methodology:One hundred breast cancer patients scheduled for 3-weekly, day-care adjuvant chemotherapy (CEF regimen) were enrolled with consecutive sampling technique, into control (n = 52) and experiment (n = 48) groups, by concealed randomization following written informed consent. Baseline data on QOL were collected before first-cycle chemotherapy using the European Organization for Research and Treatment of Cancer QLQ C30. Patients in the experimental group were taught diaphragmatic breathing techniques, systematic relaxation, and alternate nostril breathing, and Joints and Glands neck and shoulder exercises were instructed to practice twice daily at home. They were supervised in practicing these techniques while they received second, third, fourth, fifth, and sixth cycles of chemotherapy in the day-care facility. Participants in the control group received only routine care. All participants received standard post chemotherapy prescription. Data on QOL were collected from all patients during the second, third, fourth, fifth, and sixth cycles of chemotherapy.Results:The analysis revealed that at the baseline (first chemotherapy cycle), breast cancer patients in control and experimental groups were homogeneous in terms of their sociodemographic and clinical variables and QOL score. Yoga practices were effective in improving the QOL of breast cancer patients in the experimental group in the areas of global health status, physical function, role function, and emotional function and decreasing the symptoms of fatigue, insomnia, loss of appetite, and constipation, during the period of chemotherapy.Conclusion:Yoga practices comprising of relaxation techniques reduce many side effects and improve the QOL of women undergoing chemotherapy for breast cancer.

Real-World Impact of a Decision Support Tool on Colony-Stimulating Factor Use and Chemotherapy-Induced Febrile Neutropenia Among Patients With Breast Cancer.

Background: White blood cell colony-stimulating factors (CSFs) decrease the incidence of chemotherapy-induced febrile neutropenia (FN). Widespread use of CSFs that is not guideline-concordant has been reported. Among patients with breast cancer receiving chemotherapy, the ability of evidence-based decision support tools to promote risk-appropriate reductions in CSF use without increased incidence of FN has not been examined. Methods: A retrospective cohort design and US commercial claims data were used. The impact of CSF decision support was analyzed among women with breast cancer receiving first-cycle chemotherapy from April 1, 2013, to March 30, 2015. The tool was implemented as part of a prior authorization process in 9 states starting July 1, 2014. Patients were assigned to intervention (ie, states where the decision support tool had been implemented) or nonintervention states (ie, 39 states where the tool had not been implemented). CSF use and subsequent incidence of FN were compared using difference-in-difference (DID) regressions adjusting for baseline differences in FN risk factors such as comorbidities and various infections. Results: The study sample of 7,224 patients (intervention states: pre-implementation, 1,991 and post-implementation, 2,010; nonintervention states: pre-implementation, 1,569 and post-implementation, 1,654) showed no significant difference in risk factors. Before and after implementation, a significant decrease in the proportion of patients with CSF use was observed in the intervention states (75% to 69%) compared with no significant change in the nonintervention (72% to 71%) states (DID, -5.4%; 95% CI, -6.0% to -4.7%; P=.006). No significance increase in FN incidence occurred in intervention (5.0% to 5.5%) and nonintervention (5.4% to 4.8%) states (DID, 0.2%; 95% CI, -0.20 to 0.30; P=.78). Similar results were obtained in subgroups by comorbidities and in sensitivity analyses by claims-based FN definitions. Conclusions: CSF use decreased modestly after implementation of the decision support tool, with no observed changes in FN rates. Such tools can reduce practice variation to improve care standards.

Dexamethasone Modifies Cystatin C-Based Diagnosis of Acute Kidney Injury During Cisplatin-Based Chemotherapy

Background/Aims: Plasma cystatin C (pCysC) may be superior to serum creatinine (sCr) as a surrogate of GFR. However, the performance of pCysC for diagnosing acute kidney injury (AKI) after cisplatin-based chemotherapy is potentially affected by accompanying corticosteroid anti-emetic therapy and hydration. Methods: In a prospective observational study pCysC, sCr, urinary kidney injury molecule-1 (KIM-1), and urinary clusterin were measured over 2 weeks in 27 patients given first-cycle chemotherapy. The same variables were measured over 2 weeks in Sprague–Dawley rats given a single intraperitoneal injection of dexamethasone, cisplatin, or both, and in controls. Results: In patients, pCysC increases were greater than sCr 41% vs. 16%, mean paired difference 25% (95% CI: 16–34%)], relative increases were ≥ 50% in 9 patients (35%) for pCysC compared with 2 (8%) for sCr (p = 0.04) and increases in sCr were accompanied by increased KIM-1 and clusterin excretion, but increases in pCysC alone were not. In rats, dexamethasone administration produced dose-dependent increases in pCysC (and augmented cisplatin-induced increases in pCysC), but did not augment histological injury, increases in sCr, or KIM-1 and clusterin excretion. Conclusions: In the presence of dexamethasone, elevation of pCysC does not reliably diagnose AKI after cisplatin-based chemotherapy.

CYFRA 21-1 is an early predictor of chemotherapeutic effectiveness in advanced nonsmall cell lung cancer: An observational study.

Serum cytokeratin 19 fragment (CYFRA21-1) has been found to be a useful prognostic marker in lung cancer. Previous studies have revealed that change in CYFRA21-1 synchronously predicted therapeutic effectiveness in advanced nonsmall cell lung cancer (NSCLC) after the second cycle of chemotherapy. The objective of this study was to investigate the early predictive value of percentage change in serum CYFRA21-1 from pretreatment to completion of the first cycle of chemotherapy for chemotherapeutic effectiveness in advanced NSCLC patients.Ninety-seven advanced NSCLC patients with elevated serum CYFRA21-1 level (≥3.8 μg/L), who received 2 platinum-containing drugs, were included in this retrospective study. Serum CYFRA21-1 had been assayed before and after the first cycle of chemotherapy. To evaluate the effectiveness of chemotherapy, patients were allocated to disease control (DC) and progressive disease groups. The percentage changes of serum CYFRA21-1 concentration before and after first-cycle chemotherapy that occurred in each group were evaluated for their ability to predict achievement of radiologic DC, that is, to predict therapeutic effectiveness.The percentage change of serum CYFRA21-1 and the prevalence of ≥5% weight loss were higher in patients with progressive disease than in those with DC. The differences in other clinical and pathological variables including age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, cigarette smoking, histological type, gross type, clinical stage, and chemotherapy regimens of the 2 groups were not significant. Both multiple generalized linear model analysis and linear trend tests indicated that the percentage change of serum CYFRA21-1 concentration was independently and negatively linked to the effectiveness of chemotherapy for NSCLC (P < 0.01). The area under the receiver-operating characteristic curve of the percentage change in prediction of DC was 0.84 and the optimal cut-off value was17.5% (P < 0.001).The percentage change of serum CYFRA21-1 after completing the first cycle of chemotherapy was predictive of treatment effects and might be helpful in making early decisions to change chemotherapy regimens in patients with advanced NSCLC.

Risk of Neutropenia-Related Hospitalization in Patients Who Received Colony-Stimulating Factors With Chemotherapy for Breast Cancer.

Purpose To describe outcomes after granulocyte colony-stimulating factor (G-CSF) prophylaxis in patients with breast cancer who received chemotherapy regimens with low-to-intermediate risk of induction of neutropenia-related hospitalization. Patients and Methods We identified 8,745 patients age ≥ 18 years from a medical and pharmacy claims database for 14 commercial US health plans. This retrospective analysis included patients with breast cancer who began first-cycle chemotherapy from 2008 to 2013 using docetaxel and cyclophosphamide (TC); docetaxel, carboplatin, and trastuzumab (TCH); or doxorubicin and cyclophosphamide (conventional-dose AC) regimens. Primary prophylaxis (PP) was defined as G-CSF administration within 5 days of beginning chemotherapy. Outcome was neutropenia, fever, or infection-related hospitalization within 21 days of initiating chemotherapy. Multivariable regressions and number-needed-to-treat analyses were used. Results A total of 4,815 patients received TC (2,849 PP; 1,966 no PP); 2,292 patients received TCH (1,444 PP; 848 no PP); and 1,638 patients received AC (857 PP; 781 no PP) regimen. PP was associated with reduced risk of neutropenia-related hospitalization for TC (2.0% PP; 7.1% no PP; adjusted odds ratio [AOR], 0.29; 95% CI, 0.22 to 0.39) and TCH (1.3% PP; 7.1% no PP; AOR, 0.19; 95% CI, 0.12 to 0.30), but not AC (4.7% PP; 3.8% no PP; AOR, 1.21; 95% CI, 0.75 to 1.93) regimens. For the TC regimen, 20 patients (95% CI, 16 to 26) would have to be treated for 21 days to avoid one neutropenia-related hospitalization; with the TCH regimen, 18 patients (95% CI, 13 to 25) would have to be treated. Conclusion Primary G-CSF prophylaxis was associated with low-to-modest benefit in lowering neutropenia-related hospitalization in patients with breast cancer who received TC and TCH regimens. Further evaluation is needed to better understand which patients benefit most from G-CSF prophylaxis in this setting.

Toxicity-Related Factors Associated With Use of Services Among Community Oncology Patients

Community oncology practices frequently manage chemotherapy-associated toxicities, which may disrupt treatment, impair quality of life, and induce unplanned service use. We sought to understand the patterns and correlates of unplanned health care service use among patients receiving first-cycle chemotherapy at five community-based ambulatory oncology practices. A survey study examined the dichotomous outcome of unplanned service use, defined as oncologist visits, emergency department visits, and hospitalizations, resulting from toxicity-related factors. Newly diagnosed patients with breast, lung, head and neck, or colorectal cancer or non-Hodgkin lymphoma were recruited during the first chemotherapy cycle. Before beginning the second cycle of chemotherapy, patients completed a questionnaire that measured unplanned service use and overall distress, plus severity of nausea, vomiting, diarrhea, constipation, mouth sores, intravenous catheter problems, pain, fever and chills, extremity edema, and dyspnea on a 5-point scale (1, did not experience; 5, disabling). Medical record reviews captured chemotherapy doses, comorbid conditions, and supportive care interventions. Mixed-effects logistic regression was used to identify factors associated with unplanned service use, with random effects specified for each clinic. Among 106 patients (white, 98%; female, 74.5%; mean age ± standard deviation, 60 ± 11 years), frequently reported toxicities were pain, nausea, diarrhea, and constipation. Thirty-six patients (34%) reported unplanned service use: 29% reported oncologist visits, 14% reported emergency department visits, and 8% reported hospitalizations. Factors significantly associated with unplanned service use were high patient-reported distress and receipt of colony-stimulating factor. Service use resulting from toxicity-related factors occurs frequently in community oncology settings. Monitoring toxicity patterns and outcomes can inform proactive symptom management approaches to reduce toxicity burden between scheduled visits.

Factors associated with toxicity-related service use among community oncology patients.

133 Background: Chemotherapy-associated toxicities occur often, yet sparse data are available to correlate toxicities with related service use. Toxicities may disrupt treatment, impair quality of life, and induce unplanned service use. We sought to understand the frequency and correlates of unplanned service use among patients receiving first-cycle chemotherapy at 5 community-based ambulatory oncology practices in southeast Michigan. Methods: A prospective survey examined the dichotomous outcome of toxicity-related unplanned service use. Newly-diagnosed patients were recruited before the first chemotherapy cycle. At the second cycle visit, patients completed a questionnaire that measured severity of nausea, vomiting, diarrhea, constipation, mouth sores, IV catheter problems, pain, fever/chills, extremity edema, and dyspnea on a 5-point scale (1 = did not experience to 5 = disabling). They also rated distress on a 10-point scale (0 = none, 10 = worst). Patients reported unplanned oncologist visits, emergency department visits, and unplanned hospitalizations, all of which were treated as unplanned service use. Mixed-effects logistic regression was used to identify factors associated with unplanned service use, with random effects for each clinic. Results: Among 106 patients (98% white, 74.5% women, mean age 60+11), common diagnoses were breast, lung, and colorectal cancer and non-Hodgkin lymphoma. Frequent toxicities were pain, nausea, diarrhea, and constipation. Thirty-six patients (34%) reported unplanned service use: 29% reported oncologist visits, 14% reported ED visits, and 8% reported hospitalizations. 45% of the total sample and 89% of patients with unplanned service use reported at least one toxicity that was severe or disabling. Factors associated with unplanned service use were high patient-reported distress and receipt of colony-stimulating factor. Conclusions: Toxicity-related service use was common in this community oncology population. Proactive symptom assessment tools may help clinicians manage toxicities between visits. A deeper understanding of toxicity patterns and correlates can inform clinical practice guidelines in community oncology practices.

First experience of autologous peripheral blood stem cell mobilization with biosimilar granulocyte colony- stimulating factor

Mobilization techniques for autologous peripheral blood stem cell (PBSC) collection include chemotherapy followed by hematopoietic growth factors, such as granulocyte colony-stimulating factor (G-CSF). Biosimilar versions of G-CSF are now available in Europe. In this study, 40 patients with a hematological malignancy scheduled to receive biosimilar G-CSF (Zarzio(®) Sandoz Biopharmaceuticals, Paris, France) following first-cycle chemotherapy for treatment and autologous PBSC mobilization were prospectively included at a single center. These patients were compared with a historical control group who had been treated with G-CSF (Neupogen(®) Paris, France) at the same center according to the same clinical protocol. PBSC harvesting was considered successful if at least 3×10(6) CD34+ cells/kg were collected. If three consecutive CD34+ tests were below 10/μL then PBSC harvesting was not performed. Patient characteristics were similar in both groups with no significant differences in age, diagnosis, previous chemotherapy, or chemotherapy mobilization regimen. No significant differences were observed between groups in median CD34+ cells mobilized and collected, or the number of G-CSF injections and leukaphereses required to obtain the minimal CD34+ cell count. Proportion of failures was also similar in both groups. Zarziois(®) comparable to Neupogen(®) for PBSC mobilization and collection after chemotherapy and so may provide a more cost-effective strategy.

MUC1-positive circulating tumor cells and MUC1 protein predict chemotherapeutic efficacy in the treatment of metastatic breast cancer

Chemotherapy plays an important role in the treatment of metastatic breast cancer. It is important to monitor chemotherapeutic efficacy, to find a simple and efficient tool to guide treatment, and to predict the efficacy of treatment in a timely and accurate manner. This study aimed to detect mucin-1 (MUC1)– positive circulating tumor cells and MUC1 protein in the peripheral blood of patients with metastatic breast cancer and to investigate their relationship to chemotherapeutic efficacy. MUC1 mRNA was detected in the peripheral blood of 34 patients with newly diagnosed metastatic breast cancer by reverse transcription-polymerase chain reaction. The positive rates of MUC1 mRNA were 88.2% before chemotherapy and 70.6% after chemotherapy, without a significant difference (P = 0.564); MUC1 mRNA expression before chemotherapy had no correlation with treatment effectiveness (P = 0.281). The response rate of MUC1 mRNA-negative patients after first-cycle chemotherapy was significantly higher (P = 0.009) and the progression-free survival (PFS) was clearly longer than those of MUC1 mRNA-positive patients (P = 0.095). MUC1 protein in peripheral blood plasma was detected by an ELISA competitive inhibition assay. The patients with decreased MUC1 protein after chemotherapy had a significantly longer PFS than those with elevated MUC1 protein (P = 0.044). These results indicate that the outcomes of MUC1 mRNA-negative patients after chemotherapy are better than those of MUC1 mRNA-positive patients. In addition, patients with decreased expression of MUC1 protein have a better PFS.

Chemotherapy-induced nausea and vomiting in routine practice: a European perspective.

The aim of this study was to evaluate the occurrence of chemotherapy-induced nausea and vomiting (CINV) and its effect on patients' ability to carry out daily life activities following moderately to highly emetogenic, first-cycle chemotherapy in routine practice in cancer centers of four different European countries. This was a prospective, cross-sectional, nonrandomized, self-assessment study in 249 patients enrolled from cancer centers in Spain, Austria, Germany, and Switzerland. The study population consisted of 78% women, with a mean age of 54. Breast, lung, and ovarian cancers made up 75% of all cancers in the study. Patients received a mean of 2.0 chemotherapy agents and 2.5 antiemetic drugs. A total of 450 emetic episodes experienced by 243 patients was recorded over 5 days following chemotherapy, with an average of 1.8 episodes per patient (range: 0-28). A higher percentage of patients (38%) suffered from delayed compared to acute emesis (13%). Between 42% and 52% of all patients suffered from nausea (visual analogue scale > or = 5 mm) on any one day, peaking at day 3. Using the Functional Living Index for Emesis (FLIE) questionnaire, 75% of patients with nausea and 50% with vomiting reported a negative impact of these conditions on performance of daily living. CINV remains a significant problem in routine practice, particularly in the delayed phase posttreatment. Overall, CINV had a negative impact on patients' daily life.

Activation of apoptosis pathways in peripheral blood lymphocytes by in vivo chemotherapy

AbstractIn addition to myelosuppression, anticancer drugs cause rapid and persistent depletion of lymphocytes, possibly by direct apoptosis induction in mature T and B cells. Induction of apoptosis regulators was analyzed in peripheral blood lymphocytes from pediatric patients undergoing first-cycle chemotherapy for solid tumors. In vivo chemotherapy induced a significant increase in lymphocyte apoptosis ex vivo. The activation of initiator caspase-8 and effector caspase-3 and the cleavage of caspase substrates was detected 12 to 48 hours after the onset of therapy. Caspase inhibition by Z-VAD-fmk did not reduce ex vivo lymphocyte apoptosis in all patients, indicating the additional involvement of caspase-independent cell death. No evidence for the involvement of activation-induced cell death was found in the acute phase of lymphocyte depletion as analyzed by activation marker expression and sensitivity for CD95 signaling. Lymphocyte apoptosis in vivo appeared to be predominantly mediated by the mitochondrial pathway because a marked decrease of mitochondrial membrane potential (ΔΨM) was detected after 24 to 72 hours of treatment, preceded by the increased expression of Bax. Interestingly, despite the use of DNA-damaging agents, p53 remained completely undetectable throughout treatment. In contrast, in vitro treatment with cytarabine and etoposide induced p53 protein, CD95 receptor expression, CD95 sensitivity, and CD95 receptor-ligand interaction in stimulated cycling lymphocytes, but no such induction was seen in resting cells. These data suggest that chemotherapy-induced lymphocyte depletion involves distinct mechanisms of apoptosis induction, such as direct mitochondrial and caspase-dependent pathways in resting cells and p53-dependent pathways in cycling lymphocytes.