Chemotherapy Treatment Delays Research Articles

Avatrombopag for the treatment of patients with chemotherapy-induced thrombocytopenia: A case series.

Management of chemotherapy-induced thrombocytopenia (CIT) is challenging, often resulting in chemotherapy treatment delays, dose reduction, and treatment interruption. Randomized trials support the potential efficacy and safety of thrombopoietin receptor agonists in CIT management. A phase III trial of avatrombopag (AVA) demonstrated increased platelet counts (PC) in patients with solid tumours experiencing CIT. To complement those findings, this case series of six patients with solid tumours and CIT is presented. Results from these cases support the clinical benefit of AVA in improving PC and reducing the impact of CIT on tumour treatment, allowing continued therapy without dose reduction or treatment interruption.

Biological sex and chemotherapy treatment delays in patients with colorectal cancer

Biological sex and chemotherapy treatment delays in patients with colorectal cancer

Clinical significance of coadministration of moderate to strong CYP enzyme inhibitors with doxorubicin in breast cancer patients receiving AC chemotherapy.

Cytochrome P450 (CYP) enzyme inhibitors may increase the toxicity of many chemotherapies. Medication databases classify doxorubicin coadministration with CYP2D6 or CYP3A4 inhibitors as either a major interaction or contraindication. This study assessed the incidence of toxicity secondary to doxorubicin given with or without CYP enzyme inhibitors in breast cancer patients receiving doxorubicin and cyclophosphamide. This retrospective study included female breast cancer patients treated with doxorubicin and cyclophosphamide (AC). Patients were divided into three arms: no moderate or strong CYP inhibitor interactions, moderate or strong CYP2D6 inhibitor interactions, or moderate or strong CYP3A4 inhibitor interactions. Primary outcomes included incidence of doxorubicin-associated toxicity, unplanned medical visits, chemotherapy treatment delays, and doxorubicin dose reductions. The secondary endpoint was time to toxicity. There were 171 patients included (n = 20 patients in the CYP2D6 inhibitor group and n = 15 in the CYP3A4 inhibitor group). Neither CYP inhibitor group showed a difference in incidence of hepatotoxicity, cardiotoxicity, myelotoxicity, moderate/severe nausea, or treatment delays. Compared to the no CYP inhibitor group, the CYP2D6 inhibitor group experienced a higher incidence of unplanned medical visits (45% vs. 19.4%; p = 0.023) and more frequent doxorubicin dose reductions (30% vs. 7.2%; p = 0.006). The CYP3A4 inhibitor group did not differ from the no CYP inhibitor group for these outcomes. CYP inhibitors, particularly CYP2D6 inhibitors, may affect doxorubicin tolerability, as seen in this study by an increased incidence of unplanned medical visits and doxorubicin dose reductions.

Diabetes is associated with high risk of severe adverse events during chemotherapy for cancer patients: A single-center study.

Diabetes mellitus (DM) is a common comorbidity among cancer patients, but its impact on chemotherapy tolerance has not been widely studied. We aimed to compare the occurrence of severe grade 3/4 adverse events (G3/4 AEs) within 90 days of starting chemotherapy between patients with and without diabetes. We conducted a retrospective single-center study in Lille University Hospital Oncology Department, France. Patients who received the first cycle of chemotherapy for gastrointestinal, gynecological or cancer of unknown primary source between 1 May 2013 and 1 May 2016, were included. Overall, 609 patients were enrolled: 490 patients without diabetes (80.5%) and 119 patients with diabetes (19.5%). Within 90 days of starting chemotherapy, patients with diabetes had a significantly higher occurrence of AEs G3/4 compared to those with no diabetes (multivariate odds ratio [OR]: 1.57 [1.02-2.42], P=.04). More frequent G3/4 AEs in patients with diabetes were infection (26%), hematological disorders (13%), endocrine disorders (13%) and deterioration of the general condition (13%). In the year following the beginning of chemotherapy, patients with diabetes were twice as likely to be hospitalized as those without diabetes (univariate OR: 2.1 [1.40-3.15], P=.0003). After multivariate adjustment, diabetes was no longer significantly associated with the risk of hospitalization (P=.051). There were no differences between patients with and without diabetes regarding dose reduction and chemotherapy treatment delays (P=.61 and P=.30, respectively). Our study suggests the need for better consideration of DM in the personalized care plan to improve chemotherapy tolerance and quality of life of patients with DM.

Decreasing inpatient chemotherapy initiation delays at Memorial Regional Hospital.

225 Background: Between June and December 2019, hematology-oncology patients admitted for elective chemotherapy at Memorial Regional Hospital had a median delay of 10 hours to initiate chemotherapy infusion from time of admission. This contributes to increased cost to the healthcare system and patient dissatisfaction. By September 2020, elective inpatient median time from admission to chemotherapy initiation at Memorial Regional Hospital will be reduced by 20%. Methods: Multidisciplinary team formed to evaluate the time from admission to initiation of chemotherapy for patients who are electively admitted for chemotherapy in 8 Central based on time stamps available in the electronic health records. Patients electively admitted by a non MCI oncologist were excluded. Data collections included time stamp between each process from admission to administration of 1st chemotherapy. Longest time lapse between each process was counted as an occurrence/contributor to delay. Top 80% contributors identified from Pareto chart allowed team to identify countermeasures. Priority Matrix of implementation in PDSA cycle based on highest impact and ease of implementation. Statistical process control chart was developed. Results: (see table). Conclusions: PDSA Cycle 1, obtaining labs 24-48 hours prior to admission, resulted in a 10% reduction in chemotherapy initiation time. PDSA Cycle 2, enhancing “ok to treat” communication, resulted in a further reduction of time to treatment. The combination of PDSA Cycle 1 & 2 resulted in a 40% reduction in time to chemotherapy initiation, exceeding the planned aim of 20%. Balance measures reflected no reduction in the mean number of overnight stays between baseline and PDSA Cycle 2 (4 nights) that could contribute to a decreased cost. Results and recommendations to adopt at all inpatient oncology departments within the healthcare system will be presented to leadership for support. Data automation through collaborative efforts with information technology is in process to assist with continuous monitoring. Future state, the quality improvement tools gained from ASCO QTP will be utilized to evaluate and improve workflow issues in the outpatient oncology setting. Nationally recognized organizations are encouraged to propose a benchmark for admission time to first chemotherapy administration based on the evaluation of current available data. Additional studies are needed to evaluate chemotherapy treatment delays in other settings.[Table: see text]

Causes and Consequences of Chemotherapy Delays in Ambulatory Oncology Practices: A Multisite Qualitative Study.

In oncology, chemotherapy treatment delays potentially jeopardize patient safety and impede progress toward disease remission. The purpose of this study was to examine the causes and consequences of chemotherapy treatment delays and possible solutions to improve quality of care. The current authors selected a purposive sample of eight ambulatory oncology practices for ethnographic site visits, which lasted five days each. The authors conducted 290 observation hours, including clinician shadowing, and 46 semistructured interviews with clinicians (oncology nurses, physicians, and advanced practice providers). Deductive and inductive thematic analysis was performed on all data. The authors identified four primary themes from the analysis that affect delays. Future investigations should examine nurses' communication practices in the context of timely chemotherapy administration because communication and documentation technologies within healthcare settings continuously evolve.

A Multicenter Study of Romiplostim to Treat Chemotherapy-Induced Thrombocytopenia in Solid Tumors and Lymphoid Malignancies

Introduction : Chemotherapy-induced thrombocytopenia (CIT) is a common complication in cancer patients causing chemotherapy treatment delays, dose reductions, and discontinuation. A major unmet clinical need, there is no FDA-approved agent available to manage CIT. Given this, we developed clinical pathways to treat CIT at 4 large academic hospitals. Data using romiplostim to manage CIT is limited to small single-center studies and case series of solid tumor patients only. We performed the first large multicenter study of romiplostim for CIT, including both solid tumor and non-myeloid hematologic malignancy patients. Methods : We retrospectively collected demographics, cancer and chemotherapy data, romiplostim dosing, weekly platelet counts (Plt), and outcomes of romiplostim support for patients treated on institutional romiplostim CIT pathways from 2009-2019. For solid tumor patients, 2 institutions utilized intracycle dosing (romiplostim administered on average twice monthly on chemotherapy-off weeks) and 2 utilized standard weekly romiplostim dosing, facilitating comparison of dosing strategies. Romiplostim response was defined as a median on-romiplostim Plt of ≥75×109/L and at least 30×109/L higher than baseline. Baseline characteristics were analyzed for predictors of romiplostim non-response using multivariate logistic regression. Wilcoxon signed-rank and Mann-Whitney U tests compared paired and unpaired groups and Chi square and Fisher's exact tests compared categorical outcomes. Results : 173 patients (153 solid tumor, 20 lymphoid malignancy) were treated for CIT with romiplostim to facilitate ongoing chemotherapy administration, with 170 (98%) receiving a median (range) of 4 (1-36) additional chemotherapy cycles over 10 (2-125) weeks of romiplostim support. A total of 61.3 patient-years of romiplostim treatment of CIT were analyzed for effectiveness and safety. Table 1 lists baseline patient characteristics and Table 2 details chemotherapy regimens precipitating CIT and supported on romiplostim. Median per-patient Plt on romiplostim was significantly higher than baseline (all patients, 112×109/L vs. 54×109/L, P<0.001; solid tumor patients, 116×109/L vs. 60×109/L, P<0.001), Figure 1. Median romiplostim starting dose was 3 µg/kg/week, which was also the median optimized romiplostim dose (dose achieving Plt >100×109/L). While on romiplostim, bleeding occurred in 7.5% of patients and venous thromboembolism occurred in 4.6% (at Plt 65-306×109/L). Compared with intracycle romiplostim dosing, weekly romiplostim dosing resulted in higher median Plt (Figure 2) and fewer chemotherapy delays/dose reductions with no difference in bleeding or thrombotic events (Table 3). Characteristics of solid tumor patients predicting non-response to romiplostim per multivariate regression included biopsy-proven bone marrow invasion by tumor (P<0.001), prior pelvic irradiation (P=0.029), and prior temozolomide (P=0.031) (Figure 3), with only 23%, 20%, and 46% of patients, respectively, achieving a romiplostim response compared with 82% of all other solid tumor patients. Plt improvement with romiplostim was modest in patients with myeloma (N=7, median per-patient Plt 39×109/L with romiplostim vs. 19×109/L at baseline, P=0.078) and aggressive lymphoma (N=13, 47×109/L with romiplostim vs. 23×109/L at baseline, P=0.033), Figure 3, with only 35% receiving more than 1 additional chemotherapy cycle on romiplostim. All myeloma and lymphoma patients were dosed weekly and had extensive bone marrow involvement by malignancy. Conclusions : We present results of romiplostim treatment of CIT in a large cohort of 173 cancer patients, including lymphoid malignancies. Dosing strategies were compared and predictors of non-response were evaluated. Romiplostim was highly effective in solid tumor patients with CIT, allowing chemotherapy administration. Bleeding and thrombosis rates were similar to the general cancer patient population. Both weekly and intracycle dosing were effective and equally safe, but weekly dosing maintained higher Plt overall and higher Plt nadirs with fewer chemotherapy dose reductions or treatment delays. Bone marrow invasion, pelvic irradiation, and prior temozolomide predicted romiplostim non-response. Romiplostim had modest effectiveness to manage CIT in lymphoid malignancy patients with underlying bone marrow involvement. Disclosures Al-Samkari: Moderna: Consultancy. Parnes:Sunovion: Consultancy, Other: Safety monitoring board; Hoffman LaRoche: Research Funding; Genentech: Research Funding; Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Geron Corporation: Other: owning stock . Connors:Portola: Other: scientific ad boards; Abbott: Consultancy; Bristol Myer-Squibb: Consultancy, Other: Scientific Ad boards; Eli Lilly: Consultancy. Kuter:Up-to-Date: Consultancy, Honoraria, Patents & Royalties: 3 Up-to-Date chapters; Shinogi: Consultancy, Honoraria; Rigel: Consultancy, Honoraria, Research Funding; Zafgen: Consultancy, Honoraria; Platelet Disorder Support Association: Consultancy, Honoraria; UCB: Consultancy, Honoraria; Takeda (Bioverativ): Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Momenta: Consultancy, Honoraria; Merck Sharp Dohme: Consultancy, Honoraria; Actelion (Syntimmune): Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria; Principia: Consultancy, Honoraria, Research Funding; Protalex: Consultancy, Honoraria, Research Funding; Protalix: Consultancy, Honoraria; Alnylam: Consultancy, Honoraria, Research Funding; Argenx: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb (BMS): Consultancy, Honoraria, Research Funding; Caremark: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Kyowa-Kirin: Consultancy, Honoraria; Agios: Consultancy, Honoraria, Research Funding; Dova: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Shire: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Kezar: Research Funding. OffLabel Disclosure: Off-label use of the thrombopoietin receptor agonist romiplostim to treat chemotherapy-induced thrombocytopenia is discussed.

Neutropenia-Associated Outcomes in Patients With Breast Cancer Receiving Myelosuppressive Chemotherapy With Reduced Doses of Pegfilgrastim

Background: Pegfilgrastim can be utilized to prevent neutropenia-associated complications in patients receiving myelosuppressive chemotherapy for breast cancer. A common adverse event associated with pegfilgrastim is bone pain. Clinicians may opt to reduce the dose of pegfilgrastim when administering it to patients with previous severe or refractory bone pain. There is limited and conflicting evidence with regard to the safety and efficacy of this practice. The purpose of this study was to investigate the impact of administering reduced doses of pegfilgrastim on neutropenia-associated outcomes in patients with breast cancer receiving myelosuppressive chemotherapy. Methods: A retrospective chart review was conducted at a large, multistate health system with several different medical oncology practice sites. The primary outcome was the incidence of febrile neutropenia. Secondary outcomes included the incidence and severity of neutropenia, hospitalization for febrile, use of intravenous antimicrobials for febrile, delays in chemotherapy or dose reductions in chemotherapy secondary to neutropenia or febrile, rationale for dose reduction of pegfilgrastim, and improvement in bone pain. Results: A total of 80 patients received reduced dose pegfilgrastim. Most patients had their doses reduced secondary to bone pain (54%) or leukocytosis (14%). One (1.25%) patient experienced febrile neutropenia that did not require hospitalization or intravenous antimicrobials. Chemotherapy treatment delays and dose reductions secondary to neutropenia or febrile neutropenia occurred in 1 (1.25%) and 2 (2.5%) patients, respectively. Conclusion: Reduced doses of pegfilgrastim in patients receiving myelosuppressive chemotherapy for breast cancer resulted in a low incidence of neutropenia-associated events, including febrile neutropenia and grade 3/4 neutropenia.

Predictors of Adherence and Treatment Delays among African American Women Recommended to Receive Breast Cancer Chemotherapy.

Recognition of potential explanations for nonadherence or treatment delays is crucial to improving survival, particularly among African American women, for whom there is limited research assessing patient factors that influence adherence to breast cancer chemotherapy. This study sought to examine the association of patient factors such as age, income, employment, and partner status with adherence (full dose/on time) to prescribed breast cancer adjuvant chemotherapy and delays in treatment among African American women. This observational, prospective study used baseline data from the Adherence, Communication, Treatment, and Support Intervention Study that included African American women with early stage breast cancer who were recommended to receive chemotherapy. Eleven baseline demographic variables measured by a sociodemographic questionnaire were analyzed against the outcome variables of 85% adherence to chemotherapy, dichotomized as yes or no, and chemotherapy treatment delays measured as number of days. For the 121 African American women included in this study, only employment status and number of comorbidities were significant predictors for total treatment delays (incidence rate ratio [IRR] = 2.175 [p=.000]; IRR=1.234 [p=.003]) in the adjusted models. Employment status and number of comorbidities are predictors of the ability to receive timely breast cancer chemotherapy among African American women. This knowledge allows identification of patients in need of tailored supportive care to encourage adherence and prevent treatment delays.

Prognostic impact of adjuvant chemotherapy treatment delays for ovarian cancer: A cohort study

Prognostic impact of adjuvant chemotherapy treatment delays for ovarian cancer: A cohort study

Overall Survival and Metastasis Resections in Patients with Metastatic Colorectal Cancer Using Electronic Medical Records.

Treatment for patients with metastatic colorectal cancer is chemotherapy commonly combined with monoclonal antibodies against vascular endothelial growth factor (bevacizumab) or epidermal growth factor receptor (cetuximab or panitumumab), the efficacy of which has been proven in randomized controlled trials. The objective of the current retrospective study was to analyze the impact of targeted therapy, adverse events, and dose reduction on overall survival (OS) and metastasis resection rates. A hospital-based electronic informatics center was used to gather clinical data and outcome information in a "real-life" setting in a single academic hospital. A total of 178 patients were included in 2010-2013. In patients whose tumors expressed the KRAS wild type, the longest median OS was observed with irinotecan-based chemotherapy combined with bevacizumab (38months), or with cetuximab (41months). In the KRAS-mutated group, the longest median OS was observed with oxaliplatin with or without bevacizumab (34months). Beneficial liver metastasis resections were observed in 12 out of 20 patients. Patients with KRAS wild-type tumors who received cetuximab were the most likely to undergo surgery. Age was a negative predictor of OS. Patients whose chemotherapy dose was reduced to below 80% had lower OS compared to those remaining above 80%. Treatment delays in chemotherapy did not affect OS. Pulmonary embolism and infections were common but did not have an impact on OS. A hospital-based electronic informatics center provides comparable OS results, even though adverse events were frequently observed in the present study.

Abstract C25: The effect of longitudinal symptom distress and overall cancer distress on the ability of African American women to receive prescribed breast cancer chemotherapy without delay

Abstract Background: Racial breast cancer survival disparity is attributed, in part, to disparity in breast cancer treatment. Cancer related distress and symptom incidence and associated distress is historically higher than comparative white women during breast cancer chemotherapy and may influence the ability of African American women to receive full dose and timely chemotherapy. Therefore symptom incidence, distress and overall cancer related distress may be under recognized as a potential etiology of racial survival disparity. Objective: To describe the incidence and severity of symptoms and overall cancer-related distress in African American women and the association of symptom and cancer-related distress to adherence (receiving full dose prescribed without delay) to prescribed chemotherapy over three time points (baseline, midpoint and completion). Methods: A descriptive, correlational analysis was conducted of longitudinal data from a recently completed randomized controlled trial of a psycho-educational intervention entitled the Adherence, Communication, Treatment and Support (ACTS) to encourage adherence to chemotherapy for African American women with breast cancer. In the ACTS Trial we assessed symptom incidence and severity and overall cancer-related distress as potential moderators of women's willingness and/or ability to receive timely and full dose chemotherapy. We measured change of symptom incidence and severity and cancer-related distress at three time points: pre-chemotherapy (Time 1); midpoint of chemotherapy (Time 2) and completion of chemotherapy (Time 3). The Cancer Distress Thermometer (DT) was used to measure cancer-related distress; the total number of symptoms (TOTNS) and the McCorkle Symptom Distress Scale (SDS) total score were to measure symptom incidence and severity, respectively. Adherence data in terms of the number of days delayed related to the patient, clinician, and overall were extracted from medical records. Random coefficient modeling was used for analysis to accommodate the variability in the timing of treatment cycles at the key time points. Results: Subjects (n=142) were diagnosed with any stage invasive breast cancer and were undergoing chemotherapy. Results were based on 131 patients with evaluable data over at least two time points. DT, SDS, and TOTNS significantly changed over time suggesting that SDS and TOTNS increases linearly over time (SDS: b1=0.03324, p<.001; TOTNS: b1=0.02686, p<.001), whereas DT showed a slight decrease (b1=-0.00414, p=.044). Overall cancer-related distress was not significantly associated with clinical delays but was positively related to patient delays (b1=0.2445, p=.034) and total delays (b1=0.5445, p=.018). Overall total number of symptoms and symptom distress was positively related to clinical delays (b1=0.1438, p=.037) and total delays (b1=0.1669, p=.044). Conclusions: Worsening in number of symptoms, overall cancer-related distress and symptom distress over the course of chemotherapy was demonstrated among African American women receiving breast cancer chemotherapy. Worsening symptom and cancer-related distress was associated with lack of ability to receive full dose chemotherapy at the prescribed time. Implications for Practice: The influence of total number of symptoms, symptom distress and overall cancer-related distress on chemotherapy treatment delays is evident among this cohort of African American women receiving chemotherapy. Clinically this emphasizes the importance of close monitoring of cancer-related distress and symptom incidence and severity among African American women in order to allow timely breast cancer chemotherapy. Citation Format: Melissa K. Yee, Susan Sereika, Margaret Quinn Rosenzweig. The effect of longitudinal symptom distress and overall cancer distress on the ability of African American women to receive prescribed breast cancer chemotherapy without delay. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C25.

Romiplostim promotes platelet recovery in a mouse model of multicycle chemotherapy-induced thrombocytopenia

Chemotherapy-induced thrombocytopenia can lead to chemotherapy treatment delays or dose reductions. The ability of romiplostim, a thrombopoietin (TPO) mimetic, to promote platelet recovery in a mouse model of multicycle chemotherapy/radiation therapy (CRT)-induced thrombocytopenia was examined. In humans, an inverse relationship between platelet counts and endogenous TPO (eTPO) concentration exists. In a CRT mouse model, eTPO was not elevated during the first 5days after CRT treatment (the "eTPO gap"), then increased to a peak 10days after each CRT treatment in an inverse relationship to platelet counts seen in humans. To bridge the eTPO gap, mice were treated with 10-1,000μg/kg of romiplostim on day 0, 1, or 2 after CRT. In some mice, the romiplostim dose was approximately divided over 3days. Platelet recovery occurred faster with romiplostim in most conditions tested. Romiplostim doses of ≥100μg/kg given on day 0 significantly lessened the platelet nadir. Fractionating the dose over 3days did not appear to confer a large advantage. These data may provide a rationale for clinical studies of romiplostim in chemotherapy-induced thrombocytopenia.

Feasibility of Concurrent Chemoradiation in Cervical Cancer Patients From Rural Background

BackgroundConcurrent chemoradiation causes toxicities such as enteritis, hematologic toxicities which may lead to treatment interruptions, and therefore inferior outcomes. Adequate supportive care is very important to complete the scheduled protocol. Most of our patients are from rural background with a heterogeneous social background (nutrition and social support). There is paucity of literature to evaluate the tolerance of this intense treatment in these groups of patients, and hence, this study was undertaken. MethodsIn this observational study, 30 rural women having carcinoma cervix treated with concurrent chemoradiation between January and July 2013 were reviewed retrospectively. They were assessed weekly for dyselectrolytemia, enteritis, and hematologic toxicity using Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria. Treatment gaps along with reasons were recorded and correlated. ResultsMedian age of patients was 54 years. Of the patients, 43.3% were International Federation of Gynecology and Obstetrics stage II and 46.7% stage III. Grade 3 enteritis was seen in 7 of 30 patients (23.3%). None (0%) had grade 3 or higher hematologic toxicity. Dyselectrolytemia–hyponatremia (46.66%), hypokalemia (26.66%), hypocalcemia (6.66%), and hypomagnesemia (10%) were noted. Two of thirty patients (6.66%) received the planned 5 cycles, cisplatin 40 mg/m2 weekly. There were treatment interruptions in radiation in 6 (20%) and treatment delays in chemotherapy in 10 (33.33%) patients. ConclusionConcurrent chemoradiation for patients from rural areas is associated with higher acute toxicities. Regular monitoring for enteritis and dyselectrolytemias and timely intervention can help improve compliance and decrease treatment interruptions and thereby achieve the optimum treatment outcome.

Reducing breast cancer chemotherapy treatment delays by improving the transition from surgical to medical oncology.

51 Background: Delayed chemotherapy is associated with adverse clinical outcomes for breast cancer patients. Few studies have examined the processes of care within administrative staff and providers’ control that might affect the timeliness of breast cancer care. Coordinating transitions of care from surgical to medical oncology to eliminate variation is essential in ensuring timely chemotherapy for patients after surgery. This study evaluated the time of transition from surgery to medical oncology when administrative change of practice was implemented. Methods: We studied 192 consecutive breast cancer patients who received adjuvant chemotherapy. The interval between last definitive surgery and initiation of chemotherapy was calculated by integrating billing and scheduling data. Using process improvement methods a multidisciplinary team identified the opportunity to reduce delays in care coordination by scheduling the surgery, surgical post-op appointment, and medical oncology follow-up appointments simultaneously. Furthermore, responsibility for scheduling the medical oncology follow-up appointment was shifted and standardized from medical to surgical oncology administrative staff. Criteria for acceptable timeliness of appointments and escalation pathways for when provider availability was limited were established. The intervention targeted patients whose initial consultation with a breast surgeon and medical oncologist occurred on the same day, the standard practice at our institution. Results: Implementation of the interventions decreased the time from surgery to chemotherapy by six days. The standard deviation also declined, suggesting that the intervention reduced process variability. Conclusions: Standardizing administrative practices between breast surgery and medical oncology has led to a significant decrease in the time from last definitive surgery to initiation of chemotherapy and in the variability of that delay. [Table: see text]

Primary prophylactic colony-stimulating factors for the prevention of chemotherapy-induced febrile neutropenia in breast cancer patients

High-dose or dose-intensive cytotoxic chemotherapy often causes myelosuppression and severe neutropenia among cancer patients. Severe neutropenia accompanied by fever, named febrile neutropenia (FN), is the most serious manifestation of neutropenia usually requiring hospitalization and intravenous antibiotics. FN and neutropenia can lead to chemotherapy treatment delays or dose reductions, which potentially compromises the effectiveness of cancer treatment and prospects for a cure. Granulocyte-macrophage (GM) and granulocyte colony-stimulating factors (G-CSFs) are administered during chemotherapy in order to prevent or reduce the incidence or the duration of FN and neutropenia. To assess the effect of prophylactic colony-stimulating factors (CSFs) in reducing the incidence and duration of FN, and all-cause and infection-related mortality during chemotherapy in patients with breast cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, HEALTHSTAR, International Health Technology Assessment, SOMED, AMED and BIOSIS up to 8 August 2011. We also searched three Chinese databases (VIP, CNKI, CBM), the metaRegister of Controlled Trials, ClinicalTrials.gov, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and OpenGrey.eu up to August 2011. Randomized controlled trials (RCTs) comparing CSFs (any dose) with placebo or no treatment in patients with breast cancer at any stage, at risk of developing FN while undergoing any type of chemotherapy. We used pooled risk ratios (RR) with 95% confidence intervals (CIs) for binary outcomes. At least two review authors independently extracted data and assessed the risk of bias of the included studies. Trial authors were contacted for further details when information was unclear. We included eight RCTs involving 2156 participants with different stages of breast cancer and chemotherapy regimens. The trials were carried out between 1995 and 2008 and judged as being at least at moderate risk of bias. The strength of the evidence was weak for the majority of outcomes, which was mostly because of the small numbers of evaluable patients, varying definitions, as well as unclear measurements of the trials' outcomes and uncertain influences of supportive treatments on them. In most trials, the chemotherapy regimens had a risk of FN that was below the threshold at which current guidelines recommend routine primary prophylaxis with CSFs. Using CSFs significantly reduced the proportion of patients with FN (RR 0.27; 95% CI 0.11 to 0.70; number needed to treat for an additional beneficial outcome (NNTB) 12) but there was substantial heterogeneity which can be explained by possible differential effects of G-CSFs and GM-CSFs and different definitions of FN. A significant reduction in early mortality was observed in CSF-treated patients compared to placebo or no treatment (RR 0.32; 95% CI 0.13 to 0.77; NNTB 79). This finding was based on 23 fatal events in 2143 patients; wherein 19 of these 23 events occurred in one study and 17 events were attributed to progression of the disease by the study authors. For infection-related mortality, there were no significant differences between CSF and control groups (RR 0.14; 95% CI 0.02 to 1.29). In CSF-treated patients, the risk for hospitalization was significantly reduced (RR 0.14; 95% CI 0.06 to 0.30; NNTB 13), as well as the use of intravenous antibiotics (RR 0.35; 95% CI 0.22 to 0.55; NNTB 18). The risks of severe neutropenia, infection or not maintaining the scheduled dose of chemotherapy did not differ between CSF-treated and control groups. CSFs frequently led to bone pain (RR 5.88; 95% CI 2.54 to 13.60; number needed to treat for an additional harmful outcome (NNTH) 3) and injection-site reactions (RR 3.59; 95% CI 2.33 to 5.53; NNTH 3). In patients with breast cancer receiving chemotherapy, CSFs have shown evidence of benefit in the prevention of FN. There is evidence, though less reliable, of a decrease of all-cause mortality during chemotherapy and a reduced need for hospital care. No reliable evidence was found for a reduction of infection-related mortality, a higher dose intensity of chemotherapy with CSFs or diminished rates of severe neutropenia and infections. The majority of adverse events reported from CSF use were bone pain and injection-site reactions but no conclusions could be drawn regarding late-term side effects.

Lamivudine prophylaxis is effective in reducing hepatitis B reactivation and reactivation‐related mortality in chemotherapy patients: a meta‐analysis

Hepatitis B viral (HBV) reactivation in patients undergoing chemotherapy is associated with significant morbidity and mortality. Lamivudine has been suggested to be useful as a prophylaxis for HBV reactivation; however, its impact on overall survival and HBV reactivation-related liver disease survival is unclear. To determine the effect of lamivudine prophylaxis on the rate of HBV reactivation, overall survival and HBV reactivation-related survival in patients with HBV undergoing chemotherapy. A comprehensive search of MEDLINE, Cochrane Collaboration Database, reference lists and abstracts from national meetings. Statistical analysis was performed using revman. Eleven studies met the defined inclusion criteria and were included in the analysis. Two-hundred and twenty patients received lamivudine prophylaxis and 400 did not receive prophylaxis. Patients given lamivudine prophylaxis had an 87% decrease in HBV reactivation [risk ratio (RR) 0.13, 95% confidence interval (CI), 0.07-0.24] than patients not given prophylaxis [absolute risk reduction (ARR) -0.46, 95% CI, -0.61 to -0.31]. The number needed to treat to prevent one reactivation was 3. The Lamivudine prophylaxis group was also associated with a 70% reduction in reactivation-related mortality (RR 0.30, 95% CI, 0.1-0.94) compared with controls (ARR -0.03, 95% CI, 0.07-0.00). There was a reduction in treatment delays and premature termination of chemotherapy in the lamivudine prophylaxis arm (RR 0.41, 95% CI, 0.27-0.63; ARR -0.33, 95% CI, -0.33 to -0.15). There was no significant heterogeneity in the comparisons. Lamivudine prophylaxis during chemotherapy is effective in reducing the rate of HBV reactivation, and reactivation-related liver mortality. Patients with lamivudine prophylaxis had less chemotherapy treatment delays and premature termination of their chemotherapy. Few patients need to be treated to prevent reactivation. Patients with HBV undergoing chemotherapy should be started on lamivudine prophylaxis.