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.

Objectives: To determine the association between self-rated health (SRH) and functional status, comorbidity, toxicity of treatment and mortality in older patients with newly-diagnosed cancer., Materials and Methods: Patients aged 65 and over, newly diagnosed were recruited at the Jewish General Hospital, Montreal, Canada. SRH and functional status [instrumental activities of daily living (IADL), basic activities of daily living (ADL), Eastern Cooperative Oncology Group performance status (ECOG PS), frailty markers and number of comorbid conditions] were evaluated prior to the start of treatment, and at 3, 6 and 12 months (SRH only). Treatment toxicity and mortality data were abstracted from the chart. Logistic regression was also used to examine the relationship between functional status, comorbidity and SRH at baseline. Logistic and Cox regression were used to examine the association between baseline SRH and treatment toxicity/time to death., Results: There were 112 participants enrolled on this study (median age 74.1). At baseline, 74 patients (66.1%) had a good SRH and 38 patients (33.9%) had poor SRH. Only an increasing number of comorbid conditions was associated with poor SRH at baseline in both univariate and multivariable analysis. We found no association between SRH and toxicity or mortality., Conclusion: A substantial proportion had poor SRH prior to and during cancer treatment. An increasing number of comorbidities was associated with poor SRH at baseline. SRH did not predict toxicity or mortality. Attention to comorbid conditions in older patients with cancer is warranted considering their impact on SRH in this population., (© 2013.)

Purpose: Little is known about the incidence of falls in cancer patients receiving cancer treatment. The aims were to explore the number of falls older adults report in the 6 months after cancer diagnosis, and if those with a fall were more frail than those who did not fall., Methods: Secondary data analysis of a prospective pilot study that recruited patients aged 65 and older with a new cancer diagnosis. At each interview (baseline, 3- and 6-month follow-up), participants were asked if they had a fall in the previous 3 months. The frailty markers and functional status were obtained at baseline, 3- and 6-month follow-up. Chi-square and t tests were used to compare those who had a fall to those who had no fall. Univariate logistic regression analysis was conducted to explore the association between sociodemographic and health characteristics and reporting a fall., Results: Seventeen participants (18.7%) reported one or more falls in the first 6 months after cancer diagnosis. Fifteen participants reported one or more falls in the 3 months prior to the cancer diagnosis. Those who had a fall and those with no fall were not different in terms of health and functioning. None of the sociodemographic and health characteristics including the frailty markers were associated with a fall., Conclusion: A fall is common in cancer patients. More research is needed to examine the risk factors for a fall in older adults receiving cancer treatment.

Background: Although the taxanes paclitaxel and docetaxel are among the most active agents for the treatment of a wide range of cancers, tumours often develop resistance to these treatments. Cabazitaxel is a novel taxane active in both preclinical models of chemotherapy-sensitive and -resistant human tumours and patients with advanced prostate cancer that progressed following docetaxel treatment., Aim: To establish the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cabazitaxel., Patients and Methods: Cabazitaxel was administered every 3 weeks to patients with advanced solid tumours. The design allowed intrapatient dose escalation. The primary objective was to determine the MTD. Secondary objectives were to describe the safety profile, establish an appropriate dose, determine the pharmacokinetic (PK) profile of cabazitaxel, and assess antitumour activity., Results: Twenty-one patients were recruited. The MTD was reached at 30 mg/m(2), at which three of five patients experienced haematologic DLTs during the first cycle. DLTs during subsequent cycles were mainly haematologic and reported at 25 and 30 mg/m(2) dosing levels. Nail disorders and severe alopecia were not reported, and neurotoxicity, fluid retention and hypersensitivity were mild and infrequent. Cabazitaxel demonstrated linear PK, a triphasic elimination profile, with a long half-life and high clearance. Of the 19 patients evaluable for response, one unconfirmed partial response and six occurrences of stable disease were reported., Conclusions: The 25mg/m(2) dose of cabazitaxel was recommended for use in future clinical studies. In this study, cabazitaxel had an acceptable tolerability profile and activity in cervical, colorectal, endometrial and lung cancers., (Copyright © 2012. Published by Elsevier Ltd.)

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.)

Breast cancer is the second cause for brain metastases. Their incidence is rising, partly due to the therapeutic improvements which alter the natural history of breast cancer. Predictive factors for brain metastases have been identified: HER2 oncogene overexpression, lack of expression of hormone receptors, young age and triple negative status. Brain metastases prognosis remains poor with a median survival shorter than 1 year, except for solitary lesions treated by surgery or radiosurgery. We have analysed two series of data from Institut Curie (Paris and Saint-Cloud). In women younger than 65 years, with HER2 negative breast carcinoma, median survival was 7.1 months. In women older than 65 years, median survival was 4 months.

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.)

Purpose: Among all solid tumors breast cancer is the most common cause of meningeal carcinomatosis (MC). The purpose of this study was to analyze clinical and biological responses as well as overall survival in MC patients (pts) of breast primary treated with intrathecal methotrexate (MTX)., Methods and Materials: Single-center retrospective series of MC pts treated between 2000 and 2007. Chemotherapy regimen was: MTX (15 mg/day; day 1-5) and depomedrol (40 mg, day 1) plus leucoverin (12 mg IV or 25 mg PO; day 1-5). Treatment cycles were repeated every 2 weeks. The survival was analyzed according to the characteristics of the tumor considering clinical and cytological response rates to treatment., Results: The median survival was 4.5 months (range 0-53). In multivariate analysis, poor prognostic factors at diagnosis were: Performans status greater than 2 [P = 0.006, 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]. The clinical progression after one cycle and the biological response after two cycles were independently correlated with OS [P<0.001, RR = 0.09 (0.02–0.37) and P = 0.003, RR = 3.6 (1.5–8.5), respectively]. A prognostic score designed to define three groups of patients is proposed., Conclusion: Although prognosis of patients with MC is poor, 1-year overall survival rate is 25%. The proposed prognostic score may be helpful in decision but warrants further assessment and validation in prospective trials.

Aim: Phase I study of seliciclib (CYC202, R-roscovitine), an inhibitor of cyclin-dependent kinases 2, 7 and 9, causing cell cycle changes and apoptosis in cancer cells., Patients and Methods: This phase I trial aimed at defining the toxicity profile, the maximum tolerated dose (MTD), the recommended phase II dose (RD) and the main pharmacokinetic and pharmacodynamic parameters of oral seliciclib. Three schedules were evaluated: seliciclib given twice daily for 5 consecutive days every 3 weeks (schedule A), for 10 consecutive days followed by 2 weeks off (schedule B) and for 3d every 2 weeks (schedule C)., Results: Fifty-six patients received a total of 218 cycles of seliciclib. Dose-Limiting Toxicities (DLT) consisting of nausea, vomiting, asthenia and hypokalaemia occurred at 1600 mg bid for schedule A and in schedule C, DLT of hypokalaemia and asthenia occurred at 1800 mg bid. The evaluation of longer treatment duration in schedule B was discontinued because of unacceptable toxicity at lower doses. Other adverse events included transient serum creatinine increases and liver dysfunctions. Pharmacokinetic data showed that exposure to seliciclib and its carboxylate metabolite increased with increasing dose. Soluble cytokeratin 18 fragments allowed monitoring of seliciclib-induced cell death in the blood of patients treated with seliciclib at doses above 800 mg/d. One partial response in a patient with hepatocellular carcinoma and sustained tumour stabilisations were observed., Conclusions: The MTD and RD for seliciclib are 1250 mg bid for 5d every 3 weeks and 1600 mg bid for 3d every 2 weeks, respectively., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

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.

Purpose: With the aging of the population, there will be an increase in the number of older adults diagnosed with cancer. Little is known about the characteristics of older newly diagnosed cancer patients who refuse cancer treatment and how often they refuse. The aim of this paper was to describe the health and functional status characteristics of patients who refused cancer treatment., Methods: A prospective pilot study on health and vulnerability in older newly diagnosed cancer patients was conducted in the Segal Cancer Centre, Jewish General Hospital, Montreal, Canada. One hundred-twelve patients agreed to participate (response 72%). Health and functional status were assessed during the baseline interview; information on cancer treatment was obtained from the medical chart at baseline, 3 and 6 months follow-up. Descriptive techniques such as frequencies and means were used to describe the health and functional status of patients who refused treatment., Results: Of the 112 participants, 17 (15.2%) refused cancer treatment partially or completely. Of those 17, 15 were women and 2 men. Fifteen participants refused a part of their treatment upfront. Two refused all further treatment after severe toxicity. The majority of participants refusing cancer treatment were women with breast cancer and they mostly refused adjuvant chemotherapy. Participants who refused often lived alone, were less often married/living common-law, had activities of daily living disability, and often had early disease., Conclusion: The majority of older newly diagnosed cancer patients underwent the recommended cancer treatment but partial or complete cancer treatment refusal in older newly diagnosed cancer patients was not uncommon.

Introduction: Older cancer patients are possibly at an increased risk of medication-related problems because, typically, they receive many medications during their cancer treatment, both for the cancer itself and for supportive care., Objectives: The aim of this study was to describe the number and severity of potential medication problems during treatment of cancer in the first year after diagnosis. We also sought to examine whether patients receiving systemic cancer treatment had more medication-related problems at 3, 6 and 12 months than those not receiving systemic cancer treatment., Methods: This was a prospective pilot cohort study on health and vulnerability in older newly diagnosed cancer patients with 1-year follow-up. The study was conducted at Segal Cancer Centre, Jewish General Hospital, Montreal, Canada. Of 156 eligible patients, 112 agreed to participate (response 71.8%). The patients were aged >or=65 years and were newly diagnosed with breast, colorectal or lung cancer, lymphoma or multiple myeloma. Patients were asked for permission to obtain their list of medications from their pharmacist. The cancer treatment information was abstracted from the medical chart. Vigilance Santé software was used to identify the presence, type and severity of potential medication problems., Results: The median number of medications was five at baseline, seven at 3 months and six at 6 and 12 months. At baseline, 247 potential medication problems were identified, followed by 273 at 3 months, 229 at 6 months and 188 at 12 months. About half of the patients at each follow-up had one or more moderate or severe potential medication problem. Patients receiving systemic cancer treatment had significantly fewer potential problems at 3 months than patients not receiving systemic cancer treatment, but no differences were observed at 6 and 12 months. The most common warnings were contraindications, interactions and miscellaneous warnings, and the cancer treatment was involved in 12% of all potential problems., Conclusion: This study showed that the majority of older newly diagnosed cancer patients take prescribed medication and about two-thirds have potential medication problems, of which about half are of at least moderate severity. The cancer treatment was involved in only a small proportion of all potential drug problems.

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.)

Objective: In women with Human Epidermal growth Receptor 2 (HER2)-positive metastatic breast cancer (MBC), Trastuzumab has become the standard of care but previous studies have raised doubts about its economic acceptability. We carried out the first cost-effectiveness study for Trastuzumab in MBC patients, in France, that is based on observed resource use and outcomes in clinical practice., Methods: We retrospectively analyzed 47 HER2-positive MBC patients in a before-and-after design study. Nineteen patients did not receive Trastuzumab ("before" Trastuzumab introduction in clinical practice) and 28 patients received Trastuzumab (the "after" population). Direct medical costs were estimated on the basis of the physical quantities reported in the patient medical records, for the period from first metastatic progression until death or date of patient last news. Monetary values (2002 French francs) were attributed to these quantities on the basis of unit costs and incremental cost-effectiveness ratios were calculated., Results: In the Trastuzumab group, median overall survival was significantly higher (37 months vs. 19 months in the non-Ttrastuzumab group, P = 0.001) but total treatment costs were 3 times higher (€ 39,608 vs. € 12,795). The cost per additional life-year saved by Trastuzumab treatment was estimated to be € 27,492 (95% confidence interval: € 20,964-€ 34,020/year of life [bootstrapped estimation])., Conclusions: Our data suggest that despite its high unit price, Trastuzumab should be considered cost-effective in MBC patients to the extent that its incremental cost per life-year saved remains lower than gross domestic product per capita in countries like France.

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.

The clinical management of cancer in senior adult patients is based on the results of clinical trials which were performed in adults, generally younger adult patients. It is therefore difficult to assess the feasibility of such treatments, mainly chemotherapy, in older patients. The evaluation of health status is an important step in the decision making of cancer treatment in senior adults. In non Hodgkin lymphomas, the standard treatment remains chemotherapy with Rituximab. Specific protocols and treatment adaptation have been proposed in very old seniors. Surgery is a very efficient treatment in breast cancer, colorectal cancer and sometimes in non small cell lung cancer. Radiotherapy is important in the curative management of prostate cancer and in the multidisciplinary treatment of breast, colorectal and lung cancers. Chemotherapy is generally feasible in senior adults. However, Cisplatin is often too much toxic. Chemotherapy has a palliative impact in the treatment of metastatic prostate and breast cancers. It would be discussed in some high-risk groups of patients with breast and colorectal cancers. New targeted drugs are active in breast, colorectal cancers and in non Hodgkin lymphomas. Indications of treatment tailored on health status evaluation are discussed in the manuscript.

Background: Prescribing for older patients is challenging and complex. Cancer patients are at a considerable increased risk of drug-related problems because they typically receive a large number of medications during their cancer treatment, both for the cancer itself and for supportive care. Few studies have examined the scope of this problem in older newly diagnosed cancer patients., Objective: To investigate the number and severity of potential drug problems and factors associated with the occurrence of potential drug problems in older newly diagnosed cancer patients., Methods: This prospective pilot study was conducted in newly diagnosed cancer patients aged > or =65 years recruited in the Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada. Vigilance Santé software was used to identify the presence and type of potential drug problems. Logistic regression analyses were used to identify factors associated with the presence of one or more severe or moderately severe potential drug problems., Results: There were 112 participants with a mean age of 74.2 years, and 70% were women. A total of 103 patients (92%) were taking medications. The median number of medications per patient was 5 (interquartile range 3-9) and a total of 247 potential drug problems were identified. Sixty-four patients (62.1%) had a potential drug problem of any level of severity and 49 patients had a potential moderate/severe drug problem identified (47.6%). Two (0.8%) potential drug problems of the most severe level were identified, 122 warnings (49.4%) of all potential problems were of moderate severity and 123 warnings (49.8%) were at the least severe level. Factors associated with having one or more moderate/severe potential drug problems were taking five or more drugs and age > or =76 years., Conclusion: The majority of older newly diagnosed cancer patients in this study were taking at least one medication and the median number of medications per patient was 5. Published studies have shown that medication problems are common in community-dwelling older persons, but they are mostly of low severity. In this group of older newly diagnosed cancer patients, potential medication problems were also found to be common; however, half of the potential problems identified were of moderate severity.

Background: This study was performed to describe the treatment plan modifications after a geriatric oncology clinic. Assessment of health and functional status and cancer assessment was performed in older cancer patients referred to a cancer center., Patients and Methods: Between June 2004 and May 2005, 105 patients 70 years old or older referred to a geriatric oncology consultation at the Institut Curie cancer center were included. Functional status, nutritional status, mood, mobility, comorbidity, medication, social support, and place of residence were assessed. Oncology data and treatment decisions were recorded before and after this consultation. Data were analyzed for a possible correlation between one domain of the assessment and modification of the treatment plan., Results: Patient characteristics included a median age of 79 years and a predominance of women with breast cancer. About one half of patients had an independent functional status. Nearly 15% presented severe undernourishment. Depression was suspected in 53.1% of cases. One third of these patients had >2 chronic diseases, and 74% of patients took > or =3 medications. Of the 93 patients with an initial treatment decision, the treatment plan was modified for 38.7% of cases after this assessment. Only body mass index and the absence of depressive symptoms were associated with a modification of the treatment plan., Conclusion: The geriatric oncology consultation led to a modification of the cancer treatment plan in more than one third of cases. Further studies are needed to determine whether these modifications improve the outcome of these older patients.

Breast cancer is the most commonly diagnosed cancer and leading cause of cancer mortality in women worldwide. The elderly comprise a large part of the breast cancer population, and there are important specific considerations for this population. Late diagnosis and substandard local and systemic therapies are frequent, which is only partially "compensated" by a more indolent tumour behaviour due to the increasing likelihood according to age of potentially hormone sensitive tumour status. Endocrine treatment remains a key component of systemic treatment in both advanced and early setting. However chemotherapy is a valid option, with interest strengthened by proven efficacy in adjuvant setting for aggressive phenotypes, better management of side effects and attempts to develop predictive index for toxicity. The recently reported laboratory studies on potential mechanisms for resistance to endocrine therapies that involve crosstalk between growth factor signalling pathways and hormonal receptors stimulate also new therapeutic approaches.

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.

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality in women worldwide. Elderly individuals make up a large part of the breast cancer population, and there are important specific considerations for this population. The International Society of Geriatric Oncology created a task force to assess the available evidence on breast cancer in elderly individuals, and to provide evidence-based recommendations for the diagnosis and treatment of breast cancer in such individuals. A review of the published work was done with the results of a search on Medline for English-language articles published between 1990 and 2007 and of abstracts from key international conferences. Recommendations are given on the topics of screening, surgery, radiotherapy, (neo)adjuvant hormone treatment and chemotherapy, and metastatic disease. Since large randomised trials in elderly patients with breast cancer are scarce, there is little level I evidence for the treatment of such patients. The available evidence was reviewed and synthesised to provide consensus recommendations regarding the care of breast cancer in older adults.

Objective: SR271425 is a thioxanthone cytotoxic drug that induces dose-related cardiac electrophysiologic changes in preclinical models. A phase I trial was conducted to determine the maximally tolerated dose and safety profile, notably cardiac events., Methods: SR271425 was administered weekly as a 2-hour single intravenous infusion with a fixed 30 mg/m2 increment at each dose level (DL). A sustained cardiac evaluation was performed. ECG parameters were evaluated at bedside by an investigator or a cardiologist, as well as by central reading for dose limiting toxicity (DLT) determination., Results: Sixteen patients were treated. Five DLs were explored, from 75 mg/m2/wk to 195 mg/m2/wk. Fourteen patients (87.5%) experienced noncardiac adverse events related to treatment; only 2 patients presented grade 3 toxicity (nausea/vomiting and GGT increase) and no grade 4 toxicities were reported. Asymptomatic grade 1 or 2 QTcF prolongations were observed in 5 patients during central readings, and in 4 cases at bedside. One QTc-DLT, registered at bedside (grade 2), was unconfirmed at central reading, while another QTc-DLT, not noted at bedside, was highlighted by central reading. No arrhythmias or QRS prolongations were observed., Conclusions: The maximum tolerated dose of SR271425 was not reached in this trial due to early termination of the trial, not related to cardiac toxicity, following the termination of the development program by the sponsor. Sustained ECG monitoring is quite feasible in oncology phase I trials, but discrepancies between bedside and central evaluation could lead to conflicting decisions for management of patient care.

Objective: Patients initiating docetaxel chemotherapy were genotyped for CYP3A4, CYP3A5, MDR1, GSTM1, GSTT1, GSTM3, and GSTP1 to identify variability factors of docetaxel pharmacokinetics and toxicity., Methods: Genotyping was performed by direct sequencing (CYP3A4), real-time polymerase chain reaction (CYP3A5), and polymerase chain reaction-restriction fragment length polymorphism (MDR1 and GST). The clearance and area under the curve of docetaxel were calculated by use of a Bayesian approach. Absolute neutrophil count was recorded twice weekly., Results: With regard to the pharmacokinetic analysis, 58 patients were included. CYP3A4*1B carriers (*1A/*1B, n=4), who are also CYP3A5*1/*3 carriers, had a significantly higher clearance and lower dose-normalized area under the curve of docetaxel than those with the wild genotype (*1A/*1A, n=53): 55.2+/-13.5 L/h versus 37.3+/-11.7 L/h (P=.01) and 31.4+/-6.2 (microg . h/L)/(mg/m(2)) versus 52.7+/-18.2 (microg . h/L)/(mg/m(2)) (P=.005), respectively. No influence of MDR1 was evidenced. With regard to the pharmacodynamic analysis, febrile neutropenia occurred more frequently in GSTP1*A/*B carriers (31.6% versus 3.7% in *A/*A carriers and 0% in *A/*C, *B/*B, and *B/*C carriers) (P=.037). Grade 3 neutropenia occurred more frequently in 3435TT MDR1 genotype carriers: TT, 100%; CT, 77.3%; and CC, 54.5% (P=.046). No influence of GSTM1, GSTT1, or GSTM3 polymorphisms was evidenced on docetaxel toxicity., Conclusions: Patients carrying the CYP3A*1B allele may have enhanced docetaxel clearance and may be underexposed, whereas those carrying GSTP1*A/*B and 3435TT genotypes may have excessive hematologic toxicity. Further studies are warranted to determine the usefulness of genotyping before docetaxel treatment.

Oxaliplatin was brought into clinical evaluation in ovarian cancer because of the in vitro and in vivo antitumor activity observed in experimental models resistant to cisplatin. As single agent at 130 mg/m2 every 3 weeks, the objective response rates rage from 16% to 29% in patients treated after failure of one or two regimens. As first line, in a randomized trial cyclophosphamide-cisplatin versus cyclophosphamide-oxaliplatine, no significant statistical differences were observed in efficacy parameters (response rate, progression free survival and overall survival). The toxicity profile seemed to favor the oxaliplatin arm. Many associations with other available active drugs as taxanes, gemcitabine and liposomal doxorubicin were performed with promising results.

From 1981 to 1995, 1755 patients aged 70 years or over who had nonmetastatic unilateral breast carcinoma received curative local or regional treatment in our institute. Median follow-up was 8 years. The median age of these patients was 75 years (range: 70-94), and 86% were under 81 years of age. Tumors were classed as T3-4 in 24% of them; 18% had N1b/N2 tumors, and in 12% grade 3 disease was present. Only 19% were both ER and PR negative. The S phase fraction was <5% in 79% of patients. In 1046 patients (60%) modified radical mastectomy was performed, while 20% underwent lumpectomy and in 20% radiotherapy was the only treatment administered. Adjuvant endocrine therapy was given in 463 (26%) cases, and only 3% of patients received chemotherapy. The median overall survival time was 121 months. The overall cancer-related death rate was 49%. The 10-year disease-free survival (DFS) rate was 64%, and the 10-year local relapse rate was 14%. Prognostic factors determined on univariate analysis were tumor size, clinical nodal status (ER and PR), and grade. No significant difference in outcome was observed between mastectomy and conservative treatment. Parameters for which correlations with DFS were found on multivariate analysis were clinical nodal status (P < 0.0001), tumor size (P < 0.0001), ER (P < 0.0001), and PR (P = 0.04). Breast cancer in elderly women is frequently hormone-dependent (81%) with a low proliferation index. Prognostic factors are the same as in younger postmenopausal patients. More than 50% of these patients died from a cause other than their breast cancer.

Docetaxel (Taxotère) has been developed in breast cancer during the last decade. First its activity in monotherapy was proven in metastatic setting after failure of anthracycline therapy. Then the association with anthracycline demonstrated substantial activity leading to its development in early stages of breast cancer and its incorporation in adjuvant and neoadjuvant settings. Recently the first adjuvant trial comparing the association TAC versus FAC was presented. In the TAC arm, the disease free survival was better comparing with FAC (p = 0.0011) and survival was better in the subgroup with less than four positive lymph nodes. In the neoadjuvant setting, the incorporation of docetaxel after an anthracycline-based regimen (protocols Aberdeen and NSABP-B27) led to better clinical response, subsequently to better breast conservation and more important the increase of the pathological response rate. Improvement of survival has been reported in the Aderbeen study but a longer follow-up of the NSABP B27 study is required to confirm the impact of Taxotère in the outcome of breast cancer. The next step will be the development of the combination of the most active chemotherapeutic regimen with targeted therapies according to molecular characteristics of the tumor. The integration of trastuzumab with taxane-based chemotherapy has already demonstrated high activity in metastatic breast cancer with overexpression of HER2 and adjuvant trials are ongoing.

Unlabelled: Ovarian cancer is the most frequent cause of death due to gynecologic malignancy in both the United States and in Europe. A phase III investigation compared second line treatment Caelyx with topotecan in patients with advanced epithelial ovarian carcinoma who failed a first-line platinum-containing regimen. A total of 474 patients were enrolled Although no significant advantage of Caelyx over topotecan with regards to overall survival and progression was found, there were fewer adverse events in the Caelyx arm and Caelyx had significantly better quality of life profile. We conducted a cost minimization analysis of both treatment arms. Costs were estimated from the viewpoint of the hospital, over the duration of the study period (12 weeks). The frequency of adverse events was derived from the trial's CRF, the treatment patterns of adverse events was estimated for each type of adverse event and each grade for a given type of adverse event. Costs included that of the drug and management of adverse events. Because of uncertainty on actual time spent in French hospitals, administration costs were not valued. Adverse events valued in the analysis were: stomatitis/ pharyngitis, PPE, nausea/vomiting diarrhea, anemia, thrombocytopenia, neutropenia, sepsis, fever. Drug costs and costs of blood products were valued using the purchase price by the hospital, costs of tests and hospital days were estimated from the hospital's accounting system. The drug cost per patient was 8,735 euros for Caelyx and 6,196 euros for topotecan, the cost of adverse events were 528 and 3,632 euros for Caelyx and topotecan respectively, due to the high rate of adverse events in patient treated with topotecan. The total costs were 9,279 and 9,938 for Caefyx and topotecan respectively., Conclusion: the least expensive management for second line advanced ovarian cancer is Caelyx. Although the initial cost of the drug is higher, the reduced number of adverse events results in a lower total cost. Because treatment with Caelyx is also associated with a better of quality of life, this treatment strategy could be considered dominant.

Background: The objective of the current study was to analyze the impact of adjuvant chemotherapy in comparison with other prognostic parameters on the outcome of a series of patients with breast carcinoma at time of metastatic recurrence., Methods: Data from 1430 patients accrued in 8 prospective trials of anthracycline-based first-line chemotherapy conducted at the Institut Curie between 1977 and 1992 were reviewed., Results: Patients who had not received adjuvant chemotherapy had better response rates (66%) than pretreated patients (56%; P < 0.0001). Median overall survival rates after metastatic recurrence were 26 months compared with 19 months, respectively (P < 0.0001). Local and regional recurrences as well as the number of organ sites involved with metastatic disease were reduced in patients who had received adjuvant chemotherapy. In a multivariate analysis, the following parameters if present at the initiation of treatment were associated with poor outcome: elevated lactico dehydrogenase (LDH), low Karnofsky index, short disease free interval, more than two involved sites, liver involvement, and prior adjuvant chemotherapy. This adverse prognostic effect of prior adjuvant chemotherapy was independent of the type of drugs and of the duration of the treatment and was present even in the subgroup patients with prolonged disease free intervals longer than 48 months., Conclusions: Adjuvant chemotherapy adversely affects overall response rates and overall survival rates in patients with metastatic breast carcinoma treated with first-line anthracycline based chemotherapy., (Copyright 2001 American Cancer Society.)