Search

Background: We hypothesized that cancer-related inflammation might increase the risk of febrile neutropenia (FN) induced by docetaxel (DCX, Taxotere), by both affecting the exposure to DCX and the tissue sensitivity.Patients and methods: Advanced cancer patients with normal liver function, performance status (PS) <3, were included. Cytochrome P450 3A (CYP 3A) activity was estimated before the first cycle of DCX by a single determination of midazolam plasma concentration, 4 hours after 0.015 mg/kg i.v. bolus. Following the first cycle of 75–100 mg/m2 DCX, clearance and area under the concentration versus time curve (AUC) were estimated using a limited sampling strategy.Results: Among 56 assessable patients, 7 FNs occurred after first cycle (13%). In univariate analysis, high midazolam concentration and free DCX AUC were associated with severe neutropenia and FN. In addition to DCX exposure–related parameters, the risk of FN was also correlated with poor PS, baseline lymphopenia and lung cancer, while high ferritin level, indicator of an inflammatory state, reached borderline significance (P = 0.07). By multivariate analysis, total DCX AUC and baseline lymphopenia were associated with FN. High midazolam concentration was correlated with elevated ferritin level (r = 0.32; P = 0.02).Conclusion: Inflammatory status and lymphocyte count should be included in the evaluation of the benefice/risk ratio before the initiation of DCX. [ABSTRACT FROM AUTHOR]

Background: Treatment options are limited for patients with refractory metastatic breast cancer (MBC). Larotaxel (XRP9881) is a novel taxoid with preclinical activity against taxane-resistant breast cancer. The current phase II trial of larotaxel was conducted in women with taxane-treated MBC. Patients and methods: Patients were stratified by response to prior taxane therapy (resistant or nonresistant). Larotaxel 90 mg/m2 was administered as a 1-h infusion every 3 weeks. Patients were evaluated for tumor response every two cycles. A blinded external response review committee determined the overall response rate (ORR), duration of response (DOR), and time to progression (TtP) of the disease. Median survival time (MST) and safety were also evaluated. Results: One hundred and thirty patients were treated. In the nonresistant group, the ORR was 42%; median DOR 5.3 months; median TtP 5.4 months; and MST 22.6 months. In the resistant group, the ORR was 19%; median DOR 5.0 months; median TtP 1.6 months; and MST 9.8 months. The most common grade 3/4 adverse events were neutropenia (82%), fatigue (15%), diarrhea (12%), febrile neutropenia (9%), neutropenic infection (8%), and sensory neuropathy (7%). Conclusions: Larotaxel has good activity, manageable toxicity, and a favorable therapeutic index in women with taxane-pretreated MBC. [ABSTRACT FROM AUTHOR]

Purpose: Genomic tests can identify ER-positive HER2-negative localized breast cancer patients who may not benefit from adjuvant chemotherapy. Such tests seem especially interesting in "intermediate" clinico-pathological risk categories. The psychological impact of the decision uncertainty in these women remains largely unexplored. We assessed the clinical and psychological impact of EndoPredict® (EpClin), a clinico-genomic test, in these patients., Methods: This multicenter, single arm prospective study (NCT02773004) enrolled patients for which adjuvant chemotherapy was uncertain, based on predefined criteria. The primary endpoint was the proportion of change between initial adjuvant decision and final administration of chemotherapy. Secondary endpoints included post-test (Day 17) and 1-year patient reported outcomes., Results: One third of 200 evaluable patients had a high EpClin score (≥3.32867; 10 years cumulative risk of distance failure ≥10%). The overall change rate of chemotherapy decision was 72/200 (35.8%, 95% CI 29.2-42.4). Chemotherapy was withdrawn in 57 cases (28.4% [22.2-34.8]) and added in 15 (7.5% [3.8-11.2]. 6 changes (8%) were based on patients' decisions. Anxiety and distress levels increased at Day 17 when adding chemotherapy after the test result (p < 10 -7 and 0.00022 respectively), while stable in other situations. At 1-year, all patients had returned to the baseline anxiety and distress levels (mean anxiety 51.5, +/- SD = 2.5 [max. 80], mean distress 3±1 [max. 10])., Conclusions: EndoPredict ® (EpClin) is clinically useful in deciding whether or not to administer adjuvant chemotherapy in patients with intermediate risk. A single-step decision is preferable since adding chemotherapy at a later stage increases anxiety and distress., Competing Interests: Declaration of competing interest All other authors have declared no conflicts of interest., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Geriatric Assessment is an appropriate method for identifying older cancer patients at risk of life-threatening events during therapy. Yet, it is underused in practice, mainly because it is time- and resource-consuming. This study aims to identify the best screening tool to identify older cancer patients requiring geriatric assessment by comparing the performance of two short assessment tools the G8 and the Vulnerable Elders Survey (VES-13)., Patients and Methods: The diagnostic accuracy of the G8 and the (VES-13) were evaluated in a prospective cohort study of 1674 cancer patients accrued before treatment in 23 health care facilities. 1435 were eligible and evaluable. Outcome measures were multidimensional geriatric assessment (MGA), sensitivity (primary), specificity, negative and positive predictive values and likelihood ratios of the G8 and VES-13, and predictive factors of 1-year survival rate., Results: Patient median age was 78.2 years (70-98) with a majority of females (69.8%), various types of cancer including 53.9% breast, and 75.8% Performance Status 0-1. Impaired MGA, G8, and VES-13 were 80.2%, 68.4%, and 60.2%, respectively. Mean time to complete G8 or VES-13 was about five minutes. Reproducibility of the two questionnaires was good. G8 appeared more sensitive (76.5% versus 68.7%, P =  0.0046) whereas VES-13 was more specific (74.3% versus 64.4%, P<0.0001). Abnormal G8 score (HR = 2.72), advanced stage (HR = 3.30), male sex (HR = 2.69) and poor Performance Status (HR = 3.28) were independent prognostic factors of 1-year survival., Conclusion: With good sensitivity and independent prognostic value on 1-year survival, the G8 questionnaire is currently one of the best screening tools available to identify older cancer patients requiring geriatric assessment, and we believe it should be implemented broadly in daily practice. Continuous research efforts should be pursued to refine the selection process of older cancer patients before potentially life-threatening therapy.

Background: Our previous systematic review of geriatric assessment (GA) in oncology included a literature search up to November 2010. However, the quickly evolving field warranted an update. Aims of this review: (i) provide an overview of all GA instruments developed and/or in use in the oncology setting; (ii) evaluate effectiveness of GA in predicting/modifying outcomes (e.g. treatment decision impact, treatment toxicity, mortality, use of care)., Materials and Methods: Systematic review of literature published between November 2010 and 10 August 2012. English, Dutch, French and German-language articles reporting cross-sectional or longitudinal, intervention or observational studies of GA instruments were included., Data Sources: MEDLINE, EMBASE, PsycINFO, CINAHL and Cochrane Library. Two researchers independently reviewed abstracts, abstracted data and assessed the quality using standardized forms. A meta-analysis method of combining proportions was used for the outcome impact of GA on treatment modification with studies included in this update combined with those included in our previous systematic review on the use of GA., Results: Thirty-five manuscripts reporting 34 studies were identified. Quality of most studies was moderate to good. Eighteen studies were prospective, 11 cross-sectional and 5 retrospective. Three studies examined treatment decision-making impact and found decisions changed for fewer than half of assessed patients (weighted percent modification is 23.2% with 95% confidence interval (20.3% to 26.1%). Seven studies reported conflicting findings regarding predictive ability of GA for treatment toxicity/complications. Eleven studies examined GA predictions of mortality, and reported that instrumental activities of daily living, poor performance status and more numerous GA deficits were associated with increased mortality risk. Other outcomes could not be meta-analyzed., Conclusion: Consistent with our previous review, several domains of GA are associated with adverse outcomes. However, further research examining effectiveness of GA on treatment decisions and oncologic outcomes is needed.

Background: Geriatric assessment is a multidisciplinary diagnostic process that evaluates the older adult's medical, psychological, social, and functional capacity. No systematic review of the use of geriatric assessment in oncology has been conducted. The goals of this systematic review were: 1) to provide an overview of all geriatric assessment instruments used in the oncology setting; 2) to examine the feasibility and psychometric properties of those instruments; and 3) to systematically evaluate the effectiveness of geriatric assessment in predicting or modifying outcomes (including the impact on treatment decision making, toxicity of treatment, and mortality)., Methods: We searched Medline, Embase, Psychinfo, Cinahl, and the Cochrane Library for articles published in English, French, Dutch, or German between January 1, 1996, and November 16, 2010, reporting on cross-sectional, longitudinal, interventional, or observational studies that assessed the feasibility or effectiveness of geriatric assessment instruments. The quality of articles was evaluated using relevant quality assessment frameworks., Results: We identified 83 articles that reported on 73 studies. The quality of most studies was poor to moderate. Eleven studies examined psychometric properties or diagnostic accuracy of the geriatric assessment instruments used. The assessment generally took 10-45 min. Geriatric assessment was most often completed to describe a patient's health and functional status. Specific domains of geriatric assessment were associated with treatment toxicity in 6 of 9 studies and with mortality in 8 of 16 studies. Of the four studies that examined the impact of geriatric assessment on the cancer treatment decision, two found that geriatric assessment impacted 40%-50% of treatment decisions., Conclusion: Geriatric assessment in the oncology setting is feasible, and some domains are associated with adverse outcomes. However, there is limited evidence that geriatric assessment impacted treatment decision making. Further research examining the effectiveness of geriatric assessment on treatment decisions and outcomes is needed.

Background: Pilot Oncogeriatric Coordination Units (UPCOGs) were created by the French National Cancer Institute (INCA) in order to implement routine geriatric assessment of all cancer patients over 75 years of age. This article examines the role of geriatric and oncologic tools in the organization of medical oncogeriatric activities, focusing on the role and place of geriatricians., Methods: We conducted a qualitative sociological survey in the West Paris Oncogeriatric Program (POGOP), one of the Pilot Oncogeriatric Coordination Units (UPCOGs) recently created in France. Various qualitative methods were used including a review of the literature, participative observational surveys, and semidirective interviews with medical staff managing elderly cancer patients., Results: The results show that the way in which geriatric assessment procedures are implemented confirms the role of the geriatrician in the diagnosis and prevention of vulnerabilities and fragility at the time of initial diagnosis and medical decision making. Nevertheless, the articulation of these different working methods gives rise to various organizational configurations., Conclusions: The POGOP has largely contributed to clarifying medical activity in oncogeriatrics: identification of physicians, definition of shared goals, initiation, and structuring of new partnerships. Nevertheless, the geriatrician's tools, expertise, and know-how are often perceived ambiguously.

Rationale: Breast cancer is a disease of ageing. Functional independence in elderly patients, measured with the Katz activities of daily living (ADL) scale, predicts overall survival and the need for welfare support. Few prospective studies have examined the feasibility of adjuvant chemotherapy and its impact on autonomy in women over 70 years of age with high-risk breast cancer. This multicentre phase II trial was designed to assess the impact of adjuvant anthracycline-based chemotherapy on these patients' autonomy., Design and Methods: In a two-stage Fleming design, women aged ≥70 years with histologically proven hormone-receptor-negative early breast cancer and a significant risk of recurrence (pN+ or "high risk" pN0) received 4 cycles of nonpegylated liposomal doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks postoperatively, on an outpatient basis. The primary endpoint was the change in the ADL score during chemotherapy. Secondary endpoints include comprehensive geriatric, quality-of-life and acceptability assessments, tolerability, and long-term outcome. The results for the primary endpoint and other scales at completion of adjuvant chemotherapy are reported here, while long-term follow-up is not yet complete., Results: Forty patients (median age 75 [70-82]) were enrolled between February 2006 and November 2007. Chemotherapy had no deleterious impact on ADL, cognition, mental status, or the frequency of comorbidities. In contrast, the number of patients at risk of malnutrition, based on the Mini Nutritional Assessment, more than doubled between baseline and the end of chemotherapy, rising from 15% to 38%. Quality-of-life deteriorated in terms of social and role functioning, likely owing to fatigue, loss of appetite, nausea and vomiting. Treatment acceptability was good. The main adverse effect was neutropenia, 15% of the patients experiencing febrile neutropenia. No cardiac toxicity or toxic deaths occurred., Conclusion: This study demonstrates the feasibility of an adjuvant chemotherapy regimen combining nonpegylated liposomal doxorubicin and cyclophosphamide in fit elderly women <85 years with breast cancer. Although chemotherapy had an impact on social and role functioning, autonomy was not impaired and toxicity was acceptable. Special attention should be paid to nutritional status before and after treatment., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Drug interaction constitutes a major challenge in elderly cancer patients. This study investigated the number and types of medications patients and potential drug interactions in these patients., Methods: Treatments received by 105 cancer outpatients aged ≥70 years were analyzed using the French Thesaurus to identify drug-drug interactions according to four levels: contraindication, concomitant use not recommended, concomitant medications requiring precautions and concomitant medications to be taken into account., Results: The mean number of medications per patient was 4.7 (range: 0-14). Among 97 patients taking ≥2 drugs, 45 potential interactions were identified, occurring in 32 patients. No contraindication, 2 cases of concomitant use not recommended, 9 cases requiring precautions (20%) and 34 cases of concomitant medications to be taken into account were identified. Drug interactions caused respiratory distress and increased bleeding risk., Conclusion: Drug interactions are common in the elderly, but almost half of interactions were moderate., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Introduction: The concept of frailty may be useful to characterize vulnerability. The aim of this pilot study was to explore the association between frailty/functional status and treatment toxicity at 3 months and mortality at 6 months., Methods: Patients aged ≥65 years referred to the Jewish General Hospital, Montreal, with a new cancer diagnosis. Seven frailty markers and 4 functional status measures were examined. Logistic regression was used to examine the association between frailty/functional status and toxicity, and Cox models for time to death., Results: 112 participated, median age 74.1, 31 had toxicity and 15 died. At baseline, 88% had ≥1 frailty marker. Low grip strength predicted toxicity (OR 8.47, 95%CI: 1.3-53.6), ECOG performance status and ADL disability predicted time to death., Conclusion: The majority had ≥1 frailty marker. Low grip strength predicted toxicity, none of the functional measures did. Further researcher investigating the usefulness of frailty markers is needed., (2010 Elsevier Ireland Ltd. All rights reserved.)

Background: The aim of this prospective study was to report the quality of life (QoL) of older cancer patients during the first year after diagnosis and factors influencing QoL., Patients and Methods: Newly diagnosed patients aged ≥65 years were recruited for a pilot prospective cohort study at the Jewish General Hospital, Montreal, Canada. Participants were interviewed at baseline, and at 1.5, 3, 4.5, 6, and 12 months. QoL was assessed at each interview using the European Organization for the Research and Treatment of Cancer Quality of Life Core Questionnaire with 30 items. Logistic regression was conducted to determine which sociodemographic, health, and functional status characteristics were associated with decline in global health status/QoL between baseline and 12-month follow-up., Results: There were 112 participants at baseline (response rate 72%), median age of 74.1, and 70% were women. Between baseline and 12-month follow-up (n=78), 18 participants (23.1%) declined ≥10 points in global health status/QoL, while 34 participants (43.6%) remained stable and 23 participants (33.3%) improved ≥10 points. None of the sociodemographic, health, and functional status variables were associated with decline in logistic regression analyses., Conclusion: Almost 25% of older adults experienced clinically relevant decline in their QoL. Further research is needed on which factors influence decline in QoL in older adults., (© The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Research on the use of health care by older newly-diagnosed cancer patients is sparse. We investigated whether frailty predicts hospitalization, emergency department (ED) and general practitioner (GP) visits in older cancer patients in a prospective pilot study. Newly-diagnosed cancer patients aged 65 years and over were recruited in the Segal Cancer Centre, Jewish General Hospital, Montreal, Canada. One hundred ten patients participated, mean age 74.1, 70% women. During 1 year follow-up, 52 patients (47.3%) had cancer-related hospitalizations, 23 patients (20.9%) had ED visit and 17 patients (15.5%) had GP visit. No frailty marker predicted hospitalization or visits to the GP. Cognitive impairment suspicion was the only frailty marker that predicted ED visits (odds ratio 4.97; 95%CI 1.14-21.69). Although health care use was considerable in this sample, most frailty markers were not associated with health care use in this pilot study., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: Breast cancer is the leading nonhematologic cause of meningeal carcinomatosis (MC). The aim of this study was to report the outcome of patients diagnosed with breast cancer MC and treated in single institution by a high-dose intrathecal methotrexate (MTX) regimen., Methods: Ninety-one patients were diagnosed with breast cancer MC from 2000 to 2007. Intrathecal treatment was MTX 15 mg/day (days 1-5), hydrocortisone acetate (day 1) and oral folinic acid (days 1-5), repeated every 2 weeks. Patients and tumor characteristics were associated with the early clinical and biological outcome and with the overall survival (OS)., Results: The median survival was 4.5 months (range 0-53). In multivariate analysis, adverse prognostic factors at diagnosis were performance status >2 [P = 0.006, response rate (RR) = 0.33 (0.15-0.71)], more than three chemotherapy regimens before MC diagnosis [P = 0.03, RR = 0.40 (0.19-0.93)], negative hormone receptor status [P = 0.02, RR = 0.4 (0.19-0.90)] and high Cyfra 21-1 level [P = 0.048, RR = (0.09-0.99)]. Clinical progression after one cycle and biological response after two cycles were independently associated with OS [P < 0.001, RR = 0.09 (0.02-0.37) and P = 0.003, RR = 3.6 (1.5-8.5), respectively]. We propose a prognostic score in order to define three distinct groups of prognosis., Conclusions: MC presents a poor prognosis, but 1-year survival rate was 25%. This score may become a useful tool for treatment decision and clinical trials.

KRAS somatic mutations are the main predictive factor for non response to EGFR-targeted monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. We compared KRAS mutational status in the primary tumour and the corresponding metastases (1 to 4 sites) in 38 mCRC patients. KRAS mutational status was analysed using direct sequencing, SNAPShot multiplex PCR and Scorpion Taqman PCR analysis. Results showed 54% of primary tumours had KRAS mutations. A concordance of 97% between primaries and metastatic sites was observed. A tumour heterogeneity was also demonstrated in 5% of mCRC. One case with three different primary tumours harboured three different KRAS mutations, and only one was represented in the unique metastasis of this patient. We concluded there was a high concordance in the KRAS status between the primary tumour and metastases. More than one informative block and more sensitive assay may increase the accuracy of KRAS status determination.

The aim of this study was to document physicians' perceptions of cancer care for elderly patients within an oncogeriatric coordination pilot unit (UPCOG) created in Paris, France. We focused on how physicians apply new cancer care practices, how they establish new teamwork, and their experience of oncogeriatrics in everyday practice. Qualitative methods were used, including a literature review, observation of working sessions in the oncogeriatric pilot unit, and semi-structured interviews with 28 physicians. The results show how physicians' differing perceptions of geriatric oncology can hinder routine collaboration., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Cancer is an important health problem in older persons. The aim of this study was to explore how cancer specialists and geriatricians manage the treatment of older patients with cancer., Methods: Interviews using semi-structured open-ended questions., Sample: physicians working in oncology and geriatric medicine at McGill affiliated hospitals., Analysis: Grounded-theory approach., Results: 24 cancer specialists and 17 geriatricians participated. There was considerable variability with regard to assessment, treatment plan, and follow-up care and little collaboration between both specialists. The cancer specialists have more older cancer patients in their practice and collaborate with geriatricians mostly to deal with complications of cancer treatment. However, both groups of specialists expressed a desire to collaborate more and had similar research priorities., Conclusions: There was considerable variability in the management of older patients with cancer. Care for older patients with cancer might be improved by more collaboration between cancer specialists and geriatricians., (2009 Elsevier Ireland Ltd. All rights reserved.)

Background: There have been few prospective observational studies which recruited older newly-diagnosed cancer patients, and of these only some have reported information on the number needed to screen to recruit their study sample, and the number and reasons for refusal and drop-out. This paper reports on strategies to recruit older newly-diagnosed cancer patients prior to treatment into an observational prospective pilot study and to retain them during a six-month period., Methods: Medical charts of all patients in the Segal Cancer Centre aged 65 and over were screened and evaluated for inclusion. Several strategies to facilitate recruitment and retention were implemented. Reasons for exclusion, refusal and loss to follow-up were recorded. Descriptive statistics were used to report the reasons for refusal and loss to follow-up. A non-response analysis using chi-square tests and t-tests was conducted to compare respondents to those who refused to participate and to compare those who completed the study to those who were lost to follow-up. A feedback form with open-ended questions was administered following the last interview to obtain patient's opinions on the length of the interviews and conduct of this pilot study., Results: 3060 medical charts were screened and 156 eligible patients were identified. Of these 112 patients participated for a response rate of 72%. Reasons for refusal were: feeling too anxious (40%), not interested (25%), no time (12.5%), too sick (5%) or too healthy (5%) or other reasons (5%). Ninety-one patients participated in the six-month follow-up (retention 81.3%), seven patients refused follow-up (6.2%) and fourteen patients died (12.5%) during the course of the study. The median time to conduct the baseline interview was 45 minutes and 57% of baseline interviews were conducted at home. Most patients enjoyed participation and only five felt that the interviews were too long., Conclusion: It was feasible to recruit newly-diagnosed cancer patients prior to treatment although it required considerable time and effort. Once patients were included, the retention rate was high despite the fact that most were undergoing active cancer treatment.

This dose escalation study was designed to determine the recommended dose of the multi-targeted cell cycle inhibitor indisulam in combination with capecitabine in patients with solid tumours and to evaluate the pharmacokinetics of the combination. Thirty-five patients were treated with indisulam on day 1 of each 21-day cycle. Capecitabine was administered two times daily (BID) on days 1-14. Plasma concentrations of indisulam, capecitabine and its three metabolites were determined for pharmacokinetic analysis. The main dose-limiting toxicity was myelosuppression. Hand/foot syndrome and stomatitis were the major non-haematological toxicities. The recommended dose was initially established at indisulam 700 mg m(-2) and capecitabine 1250 mg m(-2) BID. However, during cycle 2 the recommended dose was poorly tolerated in three patients. A dose of indisulam 500 mg m(-2) and capecitabine 1250 mg m(-2) BID proved to be safe at cycle 1 and 2 in nine additional patients. Indisulam pharmacokinetics during cycle 1 were consistent with pharmacokinetic data from phase I mono-therapy studies. However, exposure to indisulam was remarkably increased at cycle 2 due to a drug-drug interaction between capecitabine and indisulam. Partial response was confirmed in two patients, one with colon carcinoma and the other with pancreatic carcinoma. Seventeen patients had stable disease. Indisulam (700 mg m(-2)) in combination with capecitabine (1250 mg m(-2) BID) was well tolerated during the first cycle. A dose of indisulam 500 mg m(-2) and capecitabine 1250 mg m(-2) BID was considered safe in multiple treatment cycles. The higher incidence of toxicities observed during cycle 2 can be explained by a time-dependent pharmacokinetic drug-drug interaction.