Matti S. Aapro

International Society of Geriatric Oncology Chemotherapy Taskforce: Evaluation of Chemotherapy in Older Patients—An Analysis of the Medical Literature

The elderly comprise the majority of patients with cancer and are the recipients of the greatest amount of chemotherapy. Unfortunately, there is a lack of data to make evidence-based decisions with regard to chemotherapy. This is due to the minimal participation of older patients in clinical trials and that trials have not systematically evaluated chemotherapy. This article reviews the available information with regard to chemotherapy and aging provided by a task force of the International Society of Geriatric Oncology (SIOG). Due to the lack of prospective data, the conclusions and recommendations made are a consensus of the participants. Extrapolation of data from younger to older patients is necessary, particularly to those patients older than 80 years, for which data is almost entirely lacking. The classes of drugs reviewed include alkylators, antimetabolites, anthracyclines, taxanes, camptothecins, and epipodophyllotoxins. Clinical trials need to incorporate an analysis of chemotherapy in terms of the pharmacokinetic and pharmacodynamic effects of aging. In addition, data already accumulated need to be reanalyzed by age to aid in the management of the older cancer patient.

Management of primary and advanced breast cancer in older unfit patients (medical treatment)

Elderly women constitute a large group of breast cancer patients, and after multidimensional geriatric assessment (MGA) only a minor part of them are found in perfect health (=fit), while the remaining display one or more physical or functional limitations or familial/social problems and are therefore categorized as vulnerable or frail (=unfit). Although randomized trials have not produced modest evidence that surgery impacts on ultimate survival of elderly women with hormone-responsive tumors, there is a general consensus that age alone should not prevent surgical local treatment even in unfit women due to the limited morbidity of breast surgery and to the risk of local progression. Activity and safety of AIs appear comparable in elderly women compared to younger counterparts, although concomitant cardiovascular comorbidity and osteoporosis should be closely monitored. Of note, compliance to oral therapy in unfit women and possible interferences with concomitant medications are still poorly documented issues. With the exception of high-risk node positive and estrogen-receptor negative patients, administration of adjuvant chemotherapy for estrogen-receptor positive unfit patients is rarely recommended since the uncertain gain in relapse-free survival is exceeded by the increased risk of toxicity and competitive causes of death. Endocrine-responsive metastatic disease is managed with one or more lines of endocrine treatment as in younger patients. Single agent sequential chemotherapy regimens are to be preferred to combination regimens, which are usually more toxic with a limited survival gain even in younger patients. When and how dose reductions should be applied to unfit patients is highly controversial. Trastuzumab in association with chemotherapy can be administered to elderly patients presenting HER2 overexpressing tumors, although the risk of cardiac adverse events in unfit patients is largely unknown. Bevacizumab-based combinations increase the activity and also toxicity of taxane chemotherapy, and are not a preferred option.

Approach to therapy of diffuse large B-cell lymphoma in the elderly: the International Society of Geriatric Oncology (SIOG) expert position commentary

Diffuse large B-cell lymphoma (DLBCL) is a treatable and potentially curable malignancy that is increasing in prevalence in the elderly. Until recently, older patients with this malignancy were under-represented on clinical treatment trials, so optimal therapeutic approaches for these patients were generally extrapolated from the treatment of younger patients with this disorder. Because of heightened toxicity concerns, older patients were sometimes given reduced dose therapy, potentially negatively impacting outcome. Geriatric considerations including functional status and comorbidities often were not accounted for in treatment decisions. Because of these issues as well as the lack of treatment guidelines for the elderly population, the International Society of Geriatric Oncology convened an expert panel to review DLBCL treatment in the elderly and develop consensus guidelines for therapeutic approaches in this patient population. The following treatment guidelines address initial DLBCL therapy, in both limited and advanced stage disease, as well as approaches to the relapsed and refractory patient.Diffuse large B-cell lymphoma (DLBCL) is a treatable and potentially curable malignancy that is increasing in prevalence in the elderly. Until recently, older patients with this malignancy were under-represented on clinical treatment trials, so optimal therapeutic approaches for these patients were generally extrapolated from the treatment of younger patients with this disorder. Because of heightened toxicity concerns, older patients were sometimes given reduced dose therapy, potentially negatively impacting outcome. Geriatric considerations including functional status and comorbidities often were not accounted for in treatment decisions. Because of these issues as well as the lack of treatment guidelines for the elderly population, the International Society of Geriatric Oncology convened an expert panel to review DLBCL treatment in the elderly and develop consensus guidelines for therapeutic approaches in this patient population. The following treatment guidelines address initial DLBCL therapy, in both limited and advanced stage disease, as well as approaches to the relapsed and refractory patient.

Taxanes in the treatment of breast cancer: Have we better defined their role in older patients? A position paper from a SIOG Task Force

Along with anthracyclines, taxanes are the most active cytotoxics in breast cancer (BC). Balancing efficacy against toxicity in older patients with reduced physiological reserves and significant comorbidities is both important and difficult. This is especially so given the under-representation of elderly patients in major trials and a consequent lack of evidence for drug, dose and schedule. However, BC is frequent in elderly women, who are a growing proportion of the population. Careful consideration of their care is therefore imperative. Treatment that can cure or extend the duration and quality of life should not be restricted by age, but needs to be tailored to the circumstances of elderly patients. In adjuvant use, taxane toxicity in older women is greater than in their younger counterparts, limiting its sequential combination with anthracyclines for high-risk disease unless patients are in very good health. More frequently taxanes are used alone (weekly paclitaxel, three-weekly docetaxel) or combined with cytotoxics other than anthracyclines (e.g. docetaxel plus cyclophosphamide) to reduce cardiac risk, especially in HER-2-positive patients who may develop additional trastuzumab-related cardiac events. In elderly patients with metastases, weekly paclitaxel and three-weekly docetaxel are among the cornerstones of treatment, with generally acceptable toxicity. Three-weekly docetaxel at the approved dose of 100mg/m(2) is not appropriate for the elderly. Nab-paclitaxel has efficacy comparable with solvent-based taxanes without need for steroid premedication but has been little studied in older BC patients. A head-to-head comparison with weekly paclitaxel favoured the solvent-free formulation for pathologic response, but those studied were a general adult population. Compared with early stage disease, choice of taxane and regimen in the metastatic setting relies even more on availability and preferences with regard to schedule, toxicity profile and cost, especially for recently developed formulations.