Catherine Terret

Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG) and European Society of Breast Cancer Specialists (EUSOMA)

As the mean age of the global population increases, breast cancer in older individuals will be increasingly encountered in clinical practice. Management decisions should not be based on age alone. Establishing recommendations for management of older individuals with breast cancer is challenging because of very limited level 1 evidence in this heterogeneous population. In 2007, the International Society of Geriatric Oncology (SIOG) created a task force to provide evidence-based recommendations for the management of breast cancer in elderly individuals. In 2010, a multidisciplinary SIOG and European Society of Breast Cancer Specialists (EUSOMA) task force gathered to expand and update the 2007 recommendations. The recommendations were expanded to include geriatric assessment, competing causes of mortality, ductal carcinoma in situ, drug safety and compliance, patient preferences, barriers to treatment, and male breast cancer. Recommendations were updated for screening, primary endocrine therapy, surgery, radiotherapy, neoadjuvant and adjuvant systemic therapy, and metastatic breast cancer.

Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations†

BACKGROUND Screening tools are proposed to identify those older cancer patients in need of geriatric assessment (GA) and multidisciplinary approach. We aimed to update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on the use of screening tools. MATERIALS AND METHODS SIOG composed a task group to review, interpret and discuss evidence on the use of screening tools in older cancer patients. A systematic review was carried out and discussed by an expert panel, leading to a consensus statement on their use. RESULTS Forty-four studies reporting on the use of 17 different screening tools in older cancer patients were identified. The tools most studied in older cancer patients are G8, Flemish version of the Triage Risk Screening Tool (fTRST) and Vulnerable Elders Survey-13 (VES-13). Across all studies, the highest sensitivity was observed for: G8, fTRST, Oncogeriatric screen, Study of Osteoporotic Fractures, Eastern Cooperative Oncology Group-Performance Status, Senior Adult Oncology Program (SAOP) 2 screening and Gerhematolim. In 11 direct comparisons for detecting problems on a full GA, the G8 was more or equally sensitive than other instruments in all six comparisons, whereas results were mixed for the VES-13 in seven comparisons. In addition, different tools have demonstrated associations with outcome measures, including G8 and VES-13. CONCLUSIONS Screening tools do not replace GA but are recommended in a busy practice in order to identify those patients in need of full GA. If abnormal, screening should be followed by GA and guided multidisciplinary interventions. Several tools are available with different performance for various parameters (including sensitivity for addressing the need for further GA). Further research should focus on the ability of screening tools to build clinical pathways and to predict different outcome parameters.

A Phase I and Pharmacological Study of the Platinum Polymer AP5280 Given as an Intravenous Infusion Once Every 3 Weeks in Patients with Solid Tumors

Purpose: This Phase I study was designed to determine the maximum tolerated dose, profile of adverse events, and dose-limiting toxicity of AP5280 in patients with solid tumors. Furthermore, the platinum (Pt) pharmacokinetics after AP5280 administration and preliminary antitumor activity were evaluated. AP5280 is a Pt agent linked to the water-soluble, biocompatible copolymer N-(2-hydroxypropyl)methacrylamide, which potentially increases Pt accumulation in tumors via the enhanced permeability and retention effect. In this way, it is anticipated that a higher activity of therapeutic Pt can be reached. The pharmaceutical product contains approximately 8.5% of Pt by weight and has a molecular weight of approximately 25,000. Experimental Design: Adult patients with solid tumors received AP5280 as a 1-h i.v. infusion every 21 days. Pharmacokinetics of total and unbound Pt were determined during the first treatment course and before the start of each new cycle using noncompartmental pharmacokinetic analysis. Pt-DNA adduct concentrations in WBCs and, if available, in tumor tissue were quantified using a sensitive 32P postlabeling assay. Results: Twenty-nine patients were treated at eight dose levels (90–4500 mg Pt/m2). The dose-limiting toxicity was Common Toxicity Criteria grade 3 vomiting and was experienced at 4500 mg Pt/m2 in two of six patients. The maximum tolerated dose on this schedule was therefore 4500 mg Pt/m2, and the recommended dose for a Phase II study is 3300 mg Pt/m2. Renal toxicity and myelosuppression, toxicities typically observed with cisplatin and carboplatin, were minimal for AP5280. The area under the curve of total Pt increased with increasing AP5280 dose. Plasma clearance of total Pt was 644 ± 266 ml/h, and the terminal half-life was 116 ± 46.2 h. After AP5280 administration, Pt-guanine-guanine DNA adduct concentrations in WBCs ranged from 70 to 1848 amol/μg DNA, concentrations that were substantially lower than concentrations measured after administration of therapeutic doses of cisplatin. Conclusions: AP5280 can be administered safely as a 1-h i.v. infusion at a dose of 3300 mg Pt/m2 once every 3 weeks and produces prolonged plasma exposure compared with any of the free Pt-containing drugs. However, it remains to be determined whether AP5280 can actually increase Pt delivery to the DNA of tumor cells in man as has been shown in experimental models.

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.

Multidisciplinary Approach to the Geriatric Oncology Patient

Given the dramatic demographic shift observed in developed countries, the medical community, especially oncologists, geriatricians, and primary care providers, are confronted with the expanding challenge of the management of elderly people with cancer. Ageing is associated with the accumulation of multiple and various medical and social problems. With a prevalence comparable to that of other chronic conditions in this age group, such as diabetes or dementia, cancer holds a prominent place among diseases of the elderly. The care of elderly cancer patients is fundamentally interdisciplinary. Communication and collaboration between geriatricians/primary care providers and oncologists represent key features of effective care in geriatric oncology. The combination of the disease-oriented approach of oncologists and the patient-oriented approach of geriatricians is the most powerful way to better serve this specific population. The medical approach of elderly cancer patients should ideally be under the lead of geriatricians or primary care providers sensitive to geriatric issues. Oncologists should manage the biologic consequences of the interplay between cancer and ageing. Close collaboration between clinicians will help promote active dedicated clinical research and the development of guidelines on the management of elderly people with cancer.

Early Breast Cancer in the Elderly

Breast cancer is a common tumour in the elderly and management of early disease in particular is a major challenge for oncologists and geriatricians alike. The process should begin with the Comprehensive Geriatric Assessment (CGA), which should be undertaken before any decisions about treatment are made. The important role of co-morbidities and their effect on life expectancy also need to be taken into account when making treatment decisions.The primary treatments for early breast cancer are surgery, adjuvant radiotherapy and adjuvant systemic therapy. Unfortunately, lack of a specific literature relating to early breast cancer in the elderly means formulating an evidence-based approach to treatment in this context is difficult. We have developed a new approach based on the CGA and comprehensive oncological assessment. This approach facilitates the development of an individualized oncogeriatric care plan and follow-up based on several considerations: the average patient’s life expectancy at a given age; the patient’s co-morbidities, level of dependence, and the impact of these considerations on diagnostic and therapeutic options as well as life expectancy; and the potential benefit-risk balance of treatment.In the elderly patient with breast cancer, the standard primary therapy is surgical resection (mastectomy or breast-conserving therapy). While node dissection is a major component of staging and local control of breast cancer, no data are available to guide decision-making in women aged >70 years. Primary endocrine therapy (tamoxifen) should be offered to elderly women with estrogen receptor (ER)-positive breast cancer only if they are unfit for or refuse surgery. Trials are needed to evaluate the clinical effectiveness of aromatase inhibitors as primary therapy for infirm older patients with ER-positive tumours. Breast irradiation should be recommended to older women with a life expectancy >5 years, particularly those with large tumours, positive lymph nodes or negative hormone receptors.Adjuvant hormone therapy remains a reasonable therapeutic option in elderly women with positive hormone receptor tumours. Aromatase inhibitors have demonstrated a better toxicity profile and effectiveness as adjuvant therapy than tamoxifen in young postmenopausal women but have not been specifically studied in the elderly population. The efficacy of adjuvant chemotherapy for breast cancer has been established by meta-analysis and numerous randomized trials but, again, women aged ≥70 years have rarely been included in such trials. At present, it is difficult to provide a validated recommendation for use of adjuvant chemotherapy in elderly patients with breast cancer.There are no follow-up recommendations specifically for elderly patients after treatment of early breast cancer. However, American Society of Clinical Oncology breast cancer surveillance guidelines suggest physician office visits every 3–6 months for 3 years, followed by visits every 6–12 months for 2 years, then annually. Women taking aromatase inhibitors should also undergo bone mineral density measurement every 2 years.The new approach to assessment and management of early breast cancer in the elderly outlined in this article should be considered an intermediate step because additional evidence to support clinical practice is still needed. Bearing this in mind, physicians should encourage enrolment of elderly breast cancer patients in clinical trials.

Effects of comorbidity on screening and early diagnosis of cancer in elderly people

There is currently little data showing that older adults can derive benefit from cancer screening. Advancing age is associated with an increasing prevalence of cancer and other chronic conditions, or comorbidity, and questions remain about the interactions between comorbidity and cancer screening in the elderly population. In this Review, we assess the available evidence on the effects of comorbidity on cancer screening in elderly individuals. In view of the high heterogeneity of existing data, consistent recommendations cannot be made. Decisions on cancer screening in older adults should be based on an appropriate assessment of each individuals health status and life expectancy, the benefits and harms of screening procedures, and patient preferences. We suggest that Comprehensive Geriatric Assessment might be a necessary step to identify candidates for cancer screening in the elderly population. Specific clinical trials should be done to improve the evidence and show the effectiveness and cost-effectiveness of cancer screening in older adults.

Phase I clinical and pharmacokinetic study of E7070, a novel sulfonamide given as a 5-day continuous infusion repeated every 3 weeks in patients with solid tumours. A study by the EORTC Early Clinical Study Group (ECSG)

A single-agent dose-escalating phase I study on the novel sulfonamide E7070 was performed to determine the toxicity profile and the recommended dose for phase II studies. The pharmacokinetic profile of E7070 was also determined. E7070 was administered as a continuous infusion over 5 days repeated every 3 weeks. 27 patients were treated at doses ranging from 6 to 200 mg/m(2)/day. As with other administration schedules, the dose-limiting toxicities were dose-dependent, reversible neutropenia and thrombocytopenia. Although no objective responses were observed, seven patients had stable disease. E7070 displayed a non-linear pharmacokinetic profile, especially at dose-levels greater than 24 mg/m(2)/day, with a reduction in clearance and an increase in the half-life at the higher dose levels. The risk of myelosuppression became significant with an AUC greater than 4000 microg h/ml. The recommended dose of E7070 for further studies is 96 mg/m(2)/day when administered on a 5-day continuous infusion schedule every 3 weeks.

Adjuvant docetaxel/cyclophosphamide in breast cancer patients over the age of 70: results of an observational study.

This retrospective observational study was designed to describe feasibility and tolerance of adjuvant Taxotere®/cyclophosphamide (TC) chemotherapy in women aged over 70 years with early breast cancer. Data including geriatric evaluations were collected from the medical charts of 110 patients from 14 oncology institutions in France who had completed adjuvant systemic TC (91% received at least 4 cycles). Median age was 73 years (range 70-85), 51% of patients had breast conserving surgery, 42% had a tumor smaller than 2cm and 33% had positive nodes. Geriatric assessment was performed by oncologists in 88% of patients; 55% were considered fit, 5% had geriatric syndrome and 10% had more than three comorbidities. Neutropenia was reported in 15% of patients, including febrile neutropenia and/or grade 4 in 5% for each. Primary prophylactic G-CSF was given to 49% of patients. In a selected population of elderly patients, 4 cycles of adjuvant TC is feasible without major toxicity, confirming the US Oncology trial data.

Impact of comorbidities on the treatment of non-Hodgkin's lymphoma: a systematic review.

Treating non-Hodgkin’s lymphoma in patients with comorbidities can be challenging because of possible interactions that may alter the treatment efficacy. We conducted a systematic review to determine the impact of comorbidities on various outcomes, evaluate the current data, and provide recommendations for future research. Twenty-one articles were selected. However, the study populations and design were greatly heterogeneous, and the quality of reporting was generally weak. The majority of studies demonstrated significant impact of comorbidity on survival, reporting poorer survival rates for patients with comorbidities compared to those with no comorbidities. However, the existing evidence is limited and of insufficient quality to establish solid conclusions and to guide treatment decisions. Prospective, well-designed studies are warranted.