The fall rate of older community-dwelling cancer patients.

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.

Characteristics of older newly diagnosed cancer patients refusing cancer treatments.

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.

Decision of adjuvant chemotherapy in intermediate risk luminal breast cancer patients: A prospective multicenter trial assessing the clinical and psychological impact of EndoPredict® (EpClin) use (UCBG 2-14).

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.

Participation of older newly-diagnosed cancer patients in an observational prospective pilot study: an example of recruitment and retention.

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.

Medication problems in older, newly diagnosed cancer patients in Canada: How common are they? A prospective pilot study.

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.

[Clinical management of the most important cancers in older patients]. / Prise en charge des principaux cancers chez la personne agée.

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.

Does a geriatric oncology consultation modify the cancer treatment plan for elderly patients?

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.

Management of breast cancer in elderly individuals: recommendations of the International Society of Geriatric Oncology.

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.

[Economic assessment of Caelyx versus topotecan in advanced ovarian cancer]. / Evaluation économique du Caelyx comparéau topotécan dans le traitement du cancer de l'ovaire à un stade avancé

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.

[Update on docetaxel and breast cancer]. / Actualités docetaxel dans les cancers du sein.

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.

Screening for vulnerability in older cancer patients: the ONCODAGE Prospective Multicenter Cohort Study.

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.

The relationship of self-rated health with functional status, toxicity and mortality: results of a prospective pilot study of older patients with newly-diagnosed cancer.

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.

Are frailty markers useful for predicting treatment toxicity and mortality in older newly diagnosed cancer patients? Results from a prospective pilot study.

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.

[Survival of breast cancers patients with meningeal carcinoma]. / Méningites carcinomateuses des cancers du sein.

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 (0.02­0.37) and P = 0.003, RR = 3.6 (1.5­8.5), 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.

[Brain metastases in breast cancer. Epidemiology and natural history. The Institut Curie experience]. / Métastases cérébrales dans les cancers du sein. Épidémiologie et histoire naturelle. Expérience de l'Institut Curie à travers deux études : les patientes HER2- de moins de 65 ans et les patientes de plus de 65 ans.

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.

Impact of liposomal doxorubicin-based adjuvant chemotherapy on autonomy in women over 70 with hormone-receptor-negative breast carcinoma: A French Geriatric Oncology Group (GERICO) phase II multicentre trial.

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.

Physicians' perceptions of cancer care for elderly patients: a qualitative sociological study based on a pilot geriatric oncology program.

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.

Potential medication problems in older newly diagnosed cancer patients in Canada during cancer treatment: a prospective pilot cohort study.

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.

Phase I evaluation of seliciclib (R-roscovitine), a novel oral cyclin-dependent kinase inhibitor, in patients with advanced malignancies.

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.

Concordant analysis of KRAS status in primary colon carcinoma and matched metastasis.

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.