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As the global population ages, so does the number of older people being diagnosed, treated and surviving cancer. Challenges to providing appropriate healthcare management stem from the heterogeneity common in this population. Although malnutrition is highly prevalent in older people with cancer, ranging between 30 % and 80 % according to some analyses, is associated with frailty, and has been shown to be a major risk factor for poor treatment response and worse overall survival, addressing nutrition status is not always a priority among oncology healthcare providers. Evaluation of nutritional status is a two-step process: screening identifies risk factors for reduced nutritional intake and deficits that require more in-depth assessment. Screening activities can be as simple as taking weight and BMI measurements or using short nutritional questionnaires and asking the patient about unintentional weight loss to identify potential nutritional risk. Using geriatric assessment, deficits in the nutritional domain as well as in others reveal potentially reversible geriatric and medical problems to guide specific therapeutic interventions. The authors of this paper are experts in the fields of geriatric medicine, oncology, and nutrition science and believe that there is not only substantial evidence to support regularly performing screening and assessment of nutritional status in older patients with cancer, but that these measures lead to the planning and implementation of patient-centered approaches to nutrition management and thus enhanced geriatric-oncology care. This paper presents rationale for systematic nutrition screening and assessment in older adults with cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.M.B. - Advisor to the following companies: Nutricia DANONE; Nestlé ; Fresenius; Pfizer; Novartis; Rejuvenate Biomed. Lecturer for: Nutricia DANONE; Nestlé ; Fresenius; Pfizer; Novartis. All income from the above activities goes to the institution he is working for. M.P. - Boards & Committees: BDA Prehab Sub-Group Committee. Travel grants: BDA GET Fund, RMH Charity, SIOG. Speaker fees: Fresenius Kabi, SPCC & SIOG. Research grants: Nutricia. R.B. – has participated to Advisory Boards for Nutricia Research, Eli Lilly, Novo Nordisk, Pfizer. N.M.L.B. – Advisory board: Pfizer, Abbott, Sanofi, Astellas; Travel grants: Exact Sciences, Pfizer, Lilly, Novartis; Speaker fees: Pfizer, AbbVie, Roche, Sanofi, Novartis, Servier, Gilead, AstraZeneca, Lilly. E.S-P-D-C. – Speaker fees: Amgen, Synapsis. F.S. – BMS, Sanofi, Roche, MSD, Prostrakan, Leo pharma, Janssen, Pfizer, Amgen, Pierre Fabre Oncologie, Pharmanovia, Vifor Pharma, GSK, Viatris, Helsinn. P.S. – BMS: Member of Advisory Board on cancer in the elderly (2018–2019), GSK: Conference with honoraria (2020), EISAI: Member of Advisory Board on Management of older patients with thyroid cancer (2021), AbbVie: Member of Advisory Board on Geriatric oncology in hematological malignancies (2023). The other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The benefit of chemotherapy for older patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC) is a key area of debate. Gene expression profiling (GEP) may identify patients deriving benefit, but their predictive role has not been established for older adults. We summarise evidence on efficacy, safety, and quality-of-life impacts of chemotherapy and on GEP use and impact in older HR-positive, HER2-negative EBC patients., Methods: We conducted a literature search of PubMed and Embase on publications describing prospective studies evaluating chemotherapy in older adults with HR-positive, HER2-negative EBC and on publications describing retrospective and prospective studies evaluating GEP in older adults., Results: Eight publications on chemotherapy use, including 2,035 older patients with EBC were selected. Only one trial evaluated chemotherapy survival benefits in older adults, showing no benefit. Of four studies comparing different regimens, only one showed the superiority of taxanes versus anthracyclines alone. Those investigating alternative regimens did not show improvements over standard regimens despite significant limitations. Five publications on GEP, including 445,323 older patients, were included and investigated Oncotype DX. Limited evidence shows that GEP aids treatment decisions in this population. GEP was offered less frequently to older versus younger patients. Higher Recurrence Score was prognostic for distant recurrence, but chemotherapy did not improve prognosis., Conclusions: In older patients with HR-positive, HER2-negative, chemotherapy survival benefits EBC are unclear and GEP is less used. Although its prognostic role is well established, its predictive role remains unknown., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: NMLB has received advisory fees from Pfizer and Sanofi, speaker fees from Pfizer, Sanofi, Roche and AbbVie and travel grants from Pfizer, Lilly and Genomic Health. AR has received advisory board and speaker fees from Roche, AZ, Seagen, Novartis, Pfizer, MSD and Lilly. MB has received speaker fees from Lilly, and travel grants from Pfizer. LB has received advisory board and speaker fees from AstraZeneca, Daiichi-Sankyo, Celgene, Eisai, Genomic Health, Ipsen, Lilly, Novartis, Pfizer, Pierre Fabre, Puma Biotechnology, Roche, Takeda. HW's institution received financial compensation on his behalf for advisory boards and lecture fees from Immutep Pty, MSD, AstraZeneca Ireland, Daiichi, AbbVie, Lilly, PSI CRO AG, KCE, EISAI, AstraZeneca, Roche, Congres care, Pfizer, ARIEZ, Sirtex, TRM Oncology, ORION Corporation, Novartis, Biocartes and Puma Biotech. HW's institution received an unrestricted research grant on his behalf from Roche and he received travel support from Pfizer and Roche. EB has received travel supports from AstraZeneca, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, honoraria or consultation fees from BMS, Eli Lilly, G1 Therapeutics, Pfizer, Sandoz and Seagen. KLC has received advisory fees from Genomic Health and consulting fees from Roche. SML is supported by the NCI Cancer Center Support Grant (P30CA008748). The remaining authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Evidence-based antiemetic guidelines offer predominantly consistent recommendations for chemotherapy-induced nausea and vomiting (CINV) prophylaxis. However, studies suggest that adherence to these recommendations is suboptimal. We explored inconsistencies between clinical practice and guideline-recommended treatment with a registry evaluating the effect of guideline-consistent CINV prophylaxis (GCCP) on patient outcomes., Patients and Methods: This was a prospective, non-interventional, multicentre study. The primary objective was to assess the overall (Days 1-5) complete response (CR: no emesis/no rescue use) rates in patients who received GCCP or guideline-inconsistent CINV prophylaxis (GICP) using diaries for 5 days following chemotherapy. Cycle 1 results are presented in patients who received either (1) anthracycline/cyclophosphamide (AC) highly emetogenic chemotherapy (HEC), non-AC HEC or carboplatin, with GCCP for all these groups consisting of prophylaxis with an NK 1 receptor antagonist (RA), 5-HT 3 RA and dexamethasone prior to chemotherapy or (2) moderately emetogenic chemotherapy (MEC), with GCCP consisting of a 5-HT 3 RA and dexamethasone prior to chemotherapy as per MASCC/ESMO 2016 guidelines, in place at the time of the study., Results: 1,089 patients were part of the cycle 1 efficacy evaluation. Overall GCCP was 23%. CR rates were significantly higher (P < 0.05) in patients receiving GCCP (62.2%) versus GICP (52.6%) in the overall population, as well as in the subsets of patients receiving AC/non-AC HEC (60.2% versus 47.8%), MEC (73.8% versus 57.8%) and in those non-naïve to the chemotherapy received (65.9% versus 53.8%). No impact on daily living due to CINV (FLIE assessment) was observed in 43.4% patients receiving GCCP versus 28.5% GICP (P < 0.001)., Conclusion: Consistent with prior studies, GCCP was very low; a significant benefit of almost 10% improved prevention of CINV was observed with GCCP. As per MASCC/ESMO guidelines, such an absolute difference should be practice changing. Comprehensive multifaceted strategies are needed to achieve better adherence to antiemetic guidelines., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M. Aapro: Consultant for: Helsinn, Mundipharma, Tesaro; Speakers Bureau of: Helsinn, Mundipharma, Tesaro. Z. Caprariu: Grant/research support from: Astellas, Astra Zeneca, Merck KGaA, MSD, and Pfizer; Speakers Bureau of: Roche, Eli Lilly, KRKA, G.L. Pharma - Romania. R.O. Curca: Grant/Research Support from: Abbvie, Astra Zeneca, Merck, Roche/Genentech, Helsinn; Speakers Bureau of: Abbvie, Accord, Amgen, Angelini, Astellas, AstraZeneca, Bayer, BMS, Eli Lilly, Ipsen, Johnson&Johnson, Merck KGaA, MSD, Novartis, Sandoz, Sanofi, Roche. L.Gales: Grant/Research Support from: Abbvie, Accord, Amgen, Angelini, Astellas, AstraZeneca, Bayer, BMS, Eli Lilly, Ipsen, Johnson&Johnson, Merck KGaA, MSD, Novartis, Sandoz, Sanofi, Roche, Helsinn, Tesaro; Consultant for: Abbvie, Accord, Amgen, Angelini, Astellas, AstraZeneca, Bayer, BMS, Eli Lilly, Ipsen, Johnson&Johnson, Merck KGaA, MSD, Novartis, Sandoz, Sanofi, Roche, Helsinn, Tesaro; Speakers Bureau of: Abbvie, Accord, Amgen, Angelini, Astellas, AstraZeneca, Bayer, BMS, Eli Lilly, Ipsen, Johnson&Johnson, Merck KGaA, MSD, Novartis, Sandoz, Sanofi, Roche, Helsinn, Tesaro. R. Kellnerová: Employee: Angelini Pharma Česká republika s.r.o. M. Malejčíková: Consultant for: Angelini Pharma Slovenská republika s.r.o., Amgen, Eli Lilly, Mundipharma, Novartis, Pfizer, Roche, Sandoz, Teva. M. Marinca: Consultant for Angelini Pharma, Roche; Speaker's bureau for Angelini Pharma, Roche; Grant/Research funding from Roche. E. Petru: Honoraria Received for Lectures: MSD, Angelini Pharma. M. Rubach: Consultant for: Angelini Pharma Poland. G.G. Steger: Consultant for: Amgen, TEVA, Novartis, Roche. The remaining authors disclose no conflicts., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The median age of prostate cancer diagnosis is 66 years, and the median age of men who die of the disease is eighty years. The public health impact of prostate cancer is already substantial and, given the rapidly ageing world population, can only increase. In this context, the International Society of Geriatric Oncology (SIOG) Task Forces have, since 2010, been developing guidelines for the management of senior adults with prostate cancer., Material and Methods: Since prostate cancer and geriatric oncology are both rapidly evolving fields, a new multidisciplinary Task Force was formed in 2018 to update SIOG recommendations, principally on health status screening tools and treatment. The task force reviewed pertinent articles published between June 2016 and June 2018 and abstracts from European Association of Urology (EAU), European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO) and American Society of Clinical Oncology Genito-urinary (ASCO GU) meetings over the same period, using search terms relevant to prostate cancer, the elderly, geriatric evaluation, local treatments and advanced disease. Each member of the group proposed modifications to the previous guidelines. These were collated and circulated. The final manuscript reflects the expert consensus., Results: The 2019 consensus is that men aged 75 years and older with prostate cancer should be managed according to their individual health status, and not according to age. Based on available rapid health screening tools, geriatric evaluation and geriatric interventions, the Task Force recommends that patients are classified according to health status into three groups: (1) 'healthy' or 'fit' patients should have the same treatment options as younger patients; (2) 'vulnerable' patients are candidates for geriatric interventions which-if successful-may make it appropriate for them to receive standard treatment and (3) 'frail' patients with major impairments who should receive adapted or palliative treatment. The 2019 SIOG Task Force recommendations also discuss prospects and unmet needs for health status evaluation in everyday practice in older patients with prostate cancer., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In recent decades cancer care has seen improvements in the speed and accuracy of diagnostic procedures; the effectiveness of surgery, radiation therapy and medical treatments; the power of information technology; and the development of multidisciplinary, specialist-led approaches to care. Such innovations are essential if we are to continue improving the lives of cancer patients across Europe despite financial pressures on our healthcare systems. Investment in innovation must be balanced with the need to ensure the sustainability of healthcare budgets, and all health professionals have a responsibility to help achieve this balance. It requires scrutiny of the way care is delivered; we must be ready to discontinue practices or interventions that are inefficient, and prioritise innovations that may deliver the best outcomes possible for patients within the limits of available resources. Decisions on innovations should take into account their long-term impact on patient outcomes and costs, not just their immediate costs. Adopting a culture of innovation requires a multidisciplinary team approach, with the patient at the centre and an integral part of the team. It must take a whole-system and whole-patient perspective on cancer care and be guided by high-quality real-world data, including outcomes relevant to the patient and actual costs of care; this accurately reflects the impact of any innovation in clinical practice. The European CanCer Organisation is committed to working with its member societies, patient organisations and the cancer community at large to find sustainable ways to identify and integrate the most meaningful innovations into all aspects of cancer care., (Copyright © 2017. Published by Elsevier Ltd.)

Molecular imaging using radiopharmaceuticals has a clear role in visualising the presence and extent of tumour at diagnosis and monitoring response to therapy. Such imaging provides prognostic and predictive information relevant to management, e.g. by quantifying active tumour mass using positron emission tomography/computed tomography (PET/CT). As these techniques require only pharmacologically inactive doses, age and potential frailty are generally not important. However, this may be different for therapy involving radionuclides because the radiation can impact normal bodily function (e.g. myelosuppression). Since the introduction of Iodine-131 as a targeted therapy in thyroid cancer, several radiopharmaceuticals have been widely used. These include antibodies and peptides targeting specific epitopes on cancer cells. Among therapeutic bone seeking agents, radium-223 ( 223 Ra) stands out as it results in survival gains in patients with castration-resistant prostate cancer and symptomatic bone metastases. The therapeutic use of radiopharmaceuticals in elderly cancer patients specifically has received little attention. In elderly prostate cancer patients, there may be advantages in radionuclides' ease of use and relative lack of toxicity compared with cytotoxic and cytostatic drugs. When using radionuclide therapies, close coordination between oncology and nuclear medicine is needed to ensure safe and effective use. Bone marrow reserve has to be considered. As most radiopharmaceuticals are cleared renally, dose adjustment may be required in the elderly. However, compared with younger patients there is less, if any, concern about adverse long-term radiation effects such as radiation-induced second cancers. Issues regarding the safety of medical staff, care givers and the wider environment can be managed by current precautions., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Compared with intravenous (i.v.) chemotherapy, oral administration is convenient, requires fewer healthcare resources, is generally preferred by patients, and may be appropriate in older people with breast, colorectal and lung cancers. The effects of organ dysfunction on drug metabolism and drug interactions in patients with multiple comorbidities must be considered but are not specific to oral chemotherapy. Single-agent oral chemotherapy with capecitabine or vinorelbine is active in older patients with advanced or metastatic breast cancer. Choice of treatment is based mainly on different safety profiles. In the adjuvant treatment of colorectal cancer (CRC), single-agent oral capecitabine is an effective alternative to i.v. fluorouracil (5-FU) regimens. In metastatic CRC, oral, single-agent capecitabine has recently shown encouraging median overall survival in combination with bevacizumab. In non-small cell lung cancer, fit older patients, like their younger counterparts, benefit from platinum-based doublets, with carboplatin preferred to cisplatin. Single agent vinorelbine is an option for those less suited to combination chemotherapy, and oral may be an alternative to i.v. administration. For elderly cancer patients in general, metronomic chemotherapy combines good tolerability with acceptable activity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival. In Europe, prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. The need for generally applicable, European-focused guidelines led to the formation of a European Guidelines Working Party by the European Organisation for Research and Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new systematic literature review has been undertaken to ensure that recommendations are current and provide guidance on clinical practice in Europe. We recommend that patient-related adverse risk factors, such as elderly age (≥65 years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy. It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles. We provide an expanded list of common chemotherapy regimens considered to have a high (≥20%) or intermediate (10-20%) risk of FN. Prophylactic G-CSF continues to be recommended in patients receiving a chemotherapy regimen with high risk of FN. When using a chemotherapy regimen associated with FN in 10-20% of patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Clinical evidence shows that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications where indicated. Filgrastim biosimilars are also approved for use in Europe. While other forms of G-CSF, including biosimilars, are administered by a course of daily injections, pegfilgrastim allows once-per-cycle administration. Choice of formulation remains a matter for individual clinical judgement. Evidence from multiple low level studies derived from audit data and clinical practice suggests that some patients receive suboptimal daily G-CSFs; the use of pegfilgrastim may avoid this problem., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Unlabelled: PURPOSE, PATIENTS AND METHODS: This retrospective analysis of the BRAVE study evaluated the impact of baseline risk factors and antithrombotic therapy on the risk of thrombovascular events (TVEs) in patients receiving epoetin compared to patients not receiving epoetin., Results: Baseline risk factors have a significant impact on TVE risk under epoetin therapy. More than 2 risk factors increased the risk of TVEs in patients receiving epoetin (hazard ratio [HR] 2.89, confidence interval [CI] 1.04-8.02, p value [p]=0.04). In patients on epoetin without antithrombotic therapy, the risk for TVEs was higher (HR 4.11, CI 1.37-12.4, p=0.01) compared to those who received antithrombotics (HR 1.37, CI 0.59-3.18, p=0.45)., Conclusions: Our analysis has identified several risk factors which may impact the risk of TVEs under epoetin therapy. These data suggest that antithrombotic therapy may have the potential to reduce the risk of TVEs under epoetin therapy. These findings are hypothesis-generating and need to be confirmed in a prospective, randomised study.

Objectives: To examine anaemia management in cancer patients treated with erythropoiesis-stimulating agents (ESAs) in Europe., Methods: Retrospective pharmacoepidemiologic study of 2192 patients from 307 centres. Minimum of 3 visits over 8-10 weeks with ESA treatment initiated at visit 1., Results: Most patients were treated per guidelines, except for low iron supplementation rates. Mean Hb rose from 9.54+/-0.95 g/dl to 10.88+/-1.49 g/dl at visit 3, without concomitant rise in WHO/ECOG score. Response rates were 65.0% (Hb increase (upward arrow) > or = 1 g/dl); 54.3% (Hb increase (upward arrow) > or = 1 g/dl in 8 weeks); 38.9% (haematopoietic response); 33.7% (Hb increase (upward arrow) > or = 2 g/dl) and 18.8% (Hb between 12.0 and 12.9 g/dl), Conclusions: Treatment patterns were guideline congruent, except for (intravenous) iron supplementation. Hb increased by 1.34 g/dl. A net erythropoiesis boost of Hb > or =1 g/dl is attainable in two-thirds of patients and should be condensed to 8 weeks on an individual patient basis. Anaemia management in Europe has improved significantly. The general effectiveness and relative safety of judicious ESA treatment are evident.

There is no consensus on the detailed surveillance of renal cell cancer (RCC) patients after radical resection of the kidney. Where relapse is unlikely, one reasonable option would be to confine investigations to chest X-ray and abdominal ultrasound -- carried out at 3-month intervals during the first year, but less frequently thereafter. These investigations could be supplemented by annual computerised tomography (CT) of the chest and abdomen. Where risk is intermediate or high, more frequent CT should be undertaken, taking into account the risks of repeated radiation exposure. Since the emergence of new and more effective treatments for metastatic disease, follow-up has tended to become more challenging not only with respect to disease assessment but also for evaluation of toxicity [Level 5]. The diagnostic work-up in metastatic RCC should include a history, physical examination and comprehensive blood screen. In addition, patients to be treated with targeted agents should have a thyroid function test. In patients with a relevant clinical history or who are otherwise at risk, cardiac function should be assessed, and this is also advisable in asymptomatic patients [Level 2b]. Nephrectomy is an important component of the multimodality treatment of mRCC. This procedure induces spontaneous regression of metastases in a small number of patients [Level 4]. More generally, it improves the survival of patients who subsequently receive immunotherapy [Level 1]. However, it is not yet known whether this benefit is also seen in patients treated with targeted agents [Level 2b]. Certain patients with metastases (even at multiple sites) have lesions that are resectable. Surgery is potentially curative in these cases and can be undertaken prior to use of cytokines or targeted agents [Level 2b]. Vaccine-based therapies may have potential, particularly when disease burden is low [Level 4]. The outcome of ongoing trials is awaited. Metastatic RCC responds, albeit at a low rate, to cytokines. These agents may be helpful for a subgroup of patients. However, for the great majority, and certainly for those with intermediate- or poor-risk disease, cytokines confer no benefit [Level 1b]. Choice of initial medical management in patients with metastatic clear-cell RCC should be guided by the pivotal, randomised studies. On the evidence available, the first-line therapy in patients with good- or intermediate-risk mRCC should be either sunitinib [Level 1b] or bevacizumab plus interferon [Level 1a]. In patients ineligible for sunitinib or bevacizumab plus interferon, sorafenib is an option, as is high-dose interleukin 2 if performance status is sufficiently good [Level 2b]. In patients with poor prognosis (as defined in the pivotal trial), temsirolimus is recommended [Level 1b]. In this group, sunitinib could be an alternative [Level 2b]. The role of targeted agents in the treatment of patients with RCC of non-clear-cell histologies remains to be established. In cytokine refractory patients, sorafenib is recommended [Level 1b]. Everolimus is the agent of choice when patients have progressed on a tyrosine kinase inhibitor [Level 1b].

Granulocyte colony-stimulating factors (G-CSFs) reduce febrile neutropaenia (FN) incidence but may be used inconsistently in current practice (CP). This study compared the efficacy of pegfilgrastim primary prophylaxis (PPP) with CP neutropaenia management in breast cancer. Individual patient data (N=2282) from 11 clinical trials and observational studies using chemotherapy regimens with > or =15% FN risk and PPP (6 mg, all cycles) or CP (no G-CSF or any cycle G-CSF/pegfilgrastim) were included in an integrated analysis. Most patients received docetaxel-containing regimens. A generalised linear mixed model was fitted (N=2210). Neutropaenia prophylaxis (PPP versus CP), age and disease stage influenced the incidence of FN. Overall, FN was less frequent with PPP than with CP (odds ratio [OR]: 0.124; 95% confidence interval [CI]: 0.08, 0.194; P<0.0001). Odds for cycle 1 FN, dose reductions > or =15% and FN-related hospitalisation were also significantly lower with PPP. These data support PPP in breast cancer patients receiving chemotherapy with moderately high/high FN risk.

Aim: The aim of this paper is to systematically review the use and validation of HRQOL instruments in older cancer patients., Method: A systematic review of 5 databases and 3 research registers identified studies reporting the use and validation of HRQOL instruments in cancer patients aged over 65 years from 1995 to mid 2007., Results: Thirty-one studies reported the use of HRQOL measures in older people, using a range of generic and disease-specific instruments. Little work was reported in patients aged over 80 years. All studies exhibited methodological limitations. Fourteen studies were identified with variable evidence on the psychometric properties and clinical usefulness of identified instruments., Conclusion: Our review identified that the development, validation and use of HRQOL instruments often ignore the specific needs of older people. This review highlights the need for a HRQOL instrument specifically designed to capture the issues and concerns most relevant to older cancer patients.

Purpose: To model the relationship between scores for practicing in congruence (CSs; 0-10) with EORTC guidelines for erythropoietic proteins (EPs) and haemoglobin (Hb) outcomes observed in the validation study of the RESPOND system., Methods: Thirty four patient pairs matched on cancer type and chemotherapy in pre- (retrospective; clinicians not using RESPOND) and post-cohorts (prospective; clinicians using RESPOND) followed over 4 months following EP treatment initiation. CSs quantify the extent that care was guideline-adherent. Linear and logistic regressions controlling for cohort examined Hb outcomes as a function of CSs., Results: A one-point increase in CS was associated with 0.60g/dL increase in Hb at month 4 (R(2)=0.40) and 0.56g/dL increase in Hb change from month 1-4 (R(2)=0.33). Each one-point increase in CS increased the odds of reaching Hb>or=11g/dL by 3.14 (R(2)=0.42) and Hb>or=12g/dL by 2.77 (R(2)=0.45)., Conclusion: Guideline-adherent EP treatment may improve Hb outcomes but specifically designed outcomes studies are necessary.

Background: Hand-foot syndrome (HFS) is dose-limiting and the most common cumulative toxicity associated with pegylated liposomal doxorubicin (PLD). It can cause considerable discomfort and lead to therapy interruption. Numerous approaches to HFS management have been reported, but there is no consensus., Methods: Published literature (identified via Medline and internet search) and expert experience regarding HFS and its pathogenesis, incidence, risk factors, prevention and treatment in patients undergoing treatment with PLD were collected and reviewed by a panel of experts. A consensus technique was used to develop recommendations., Findings: The pathogenesis of PLD-associated HFS has been recently elucidated. Systems used to grade, prevent and treat HFS in individuals treated with PLD vary widely. A randomised clinical study demonstrated that PLD dose intensity reduction can prevent HFS. While there is limited literature support, patient education and supportive measures were endorsed by the expert panel as effective strategies for HFS prevention and treatment. An easy to use HFS grading and management algorithm was developed, early signs and symptoms of HFS outlined and specific recommendations for supportive care developed., Interpretation: The paucity of data on the management of PLD-associated HFS led the expert panel to develop consensus-based recommendations. Patient education and supportive measures are important elements in the management of HFS and dose intensity reduction has documented efficacy in prevention. At a PLD dose intensity not exceeding 10mg/m(2) weekly, HFS can be easily managed. Phase III research to support the efficacy other interventions is lacking.

Febrile neutropenia (FN) is a severe consequence of myelosuppressive therapy. The European Organisation for Research and Treatment of Cancer recently published guidelines on the use of granulocyte colony-stimulating factor (G-CSF) to prevent FN in patients with malignant disease. In this review, the impact of these guidelines on breast cancer treatment is discussed. A brief summary of FN in breast cancer is given, and patient-related and treatment schedule-related risk factors for FN are reviewed for the adjuvant/neoadjuvant and metastatic disease settings. Primary G-CSF support is recommended if the overall FN risk is > or = 20%, or if a reduction in dose-intensity is associated with a poorer outcome. Any formulation of G-CSF is recommended. The utility of G-CSF in reducing the incidence of FN and enabling treatment regimens is discussed.

A multidisciplinary approach is mandatory for patients with gastric cancer. Patients should be managed by an experienced team of physicians. The outcome of patients is related to the experience of the multidisciplinary team. Surgery is the cornerstone of the management of patients with resectable gastric cancer. The standard recommendations for resectable gastric adenocarcinoma are free-margin surgery with at least D1 resection combined to removal of a minimum of 15 lymph nodes. It has been shown that the outcome of patients with resectable gastric cancer can be improved by a strategy of perioperative (pre- and postoperative) chemotherapy or by postoperative chemoradiotherapy. The evidence comes from large randomised phase 3 studies. In the treatment of unresectable, locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma, no chemotherapy combination was accepted as the gold standard. Cisplatin/5-FU (CF) and ECF (epirubicin plus CF) regimens have been investigated widely in clinical studies and were until recently presented as the reference regimens. Despite a relative chemosensitivity of gastric cancer, a low rate of complete response was obtained, the response duration was short and patients' outcomes remained poor. Recently, new options have been introduced in the management of advanced gastric cancer. It has been shown that capecitabine is at least as good as 5-FU and that oxaliplatin at least as good as cisplatin in these combinations. It has also been demonstrated that the addition of docetaxel to CF resulted in statistically significant improved efficacy endpoints (including patient's quality of life), but also in an increased toxicity. The DCF regimen (docetaxel, cisplatin and 5-FU) has become, therefore, a new active option in advanced gastric cancer in selected patients in good condition. Further randomised trials are therefore to be designed to further improve chemotherapy by modifying and optimising the chemotherapy regimens, and investigating novel treatment combinations. The addition of biological agents to the optimal chemotherapy regimen may achieve further improvements in efficacy.

A society of geriatric oncology (SIOG) task force reviewed information from the literature (in PubMed) on bisphosphonates in elderly patients with bone metastases until December 2005. Additional pertinent data were obtained from the manufacturers. Bisphosphonates are recommended in the elderly with bone metastases to prevent skeletal-related events. Intravenous formulations are preferred for the treatment of hypercalcaemia. It has been recognised that zoledronic acid, ibandronate and pamidronate can effectively contribute in relieving metastatic bone pain. Creatinine clearance should be monitored in every patient, and a less renally toxic agent should be used where evidence of similar efficacy is available. The assessment and optimisation of hydration status is recommended. Due to the risk from osteonecrosis of the jaw, routine oral examination and treatment of dental problems by a dental team is recommended before bisphosphonates. Physicians should choose the most appropriate bisphosphonate. Safety precautions are particularly important in elderly patients. Further research is needed in this population.

In vitro and animal model studies have shown erythropoietin receptor (Epo-R) mRNA and/or protein may be present in a range of human tumours and cancer cell lines, and erythropoiesis-stimulating agents (ESAs) have been reported to have tumour cell growth-modulating effects. Following a review of the literature, we conclude that considerations must be made when interpreting data from the preclinical studies. First, supraphysiological doses of ESAs were usually used. Second, there are no well validated, commercially available antibodies for identifying the presence and functionality of Epo-R at the protein level, either intracellularly or on the cell surface. Data from previous studies that used antibodies only for Epo-R detection must therefore be interpreted with caution. Together with diverging results in the literature, these methodological limitations indicate that findings from preclinical studies must not be over-translated in terms of their clinical relevance to patients with cancer.

A SIOG taskforce was formed to discuss best clinical practice for elderly cancer patients with renal insufficiency. This manuscript outlines recommended dosing adjustments for cancer drugs in this population according to renal function. Dosing adjustments have been made for drugs in current use which have recommendations in renal insufficiency and the elderly, focusing on drugs which are renally eliminated or are known to be nephrotoxic. Recommendations are based on pharmacokinetic and/or pharmacodynamic data where available. The taskforce recommend that before initiating therapy, some form of geriatric assessment should be conducted that includes evaluation of comorbidities and polypharmacy, hydration status and renal function (using available formulae). Within each drug class, it is sensible to use agents which are less likely to be influenced by renal clearance. Pharmacokinetic and pharmacodynamic data of anticancer agents in the elderly are needed in order to maximise efficacy whilst avoiding unacceptable toxicity.

Anaemia is frequently diagnosed in patients with cancer, and may have a detrimental effect on quality of life (QoL). We previously conducted a systematic literature review (1996-2003) to produce evidence-based guidelines on the use of erythropoietic proteins in anaemic patients with cancer.[Bokemeyer C, Aapro MS, Courdi A, et al. EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer. Eur J Cancer 2004;40:2201-2216.] We report here an update to these guidelines, including literature published through to November 2005. The results of this updated systematic literature review have enabled us to refine our guidelines based on the full body of data currently available. Level I evidence exists for a positive impact of erythropoietic proteins on haemoglobin (Hb) levels when administered to patients with chemotherapy-induced anaemia or anaemia of chronic disease, when used to prevent cancer anaemia, and in patients undergoing cancer surgery. The addition of further Level I studies confirms our recommendation that in cancer patients receiving chemotherapy and/or radiotherapy, treatment with erythropoietic proteins should be initiated at a Hb level of 9-11 g/dL based on anaemia-related symptoms rather than a fixed Hb concentration. Early intervention with erythropoietic proteins may be considered in asymptomatic anaemic patients with Hb levels 11.9 g/dL provided that individual factors like intensity and expected duration of chemotherapy are considered. Patients whose Hb level is below 9 g/dL should primarily be evaluated for need of transfusions potentially followed by the application of erythropoietic proteins. We do not recommend the prophylactic use of erythropoietic proteins to prevent anaemia in patients undergoing chemotherapy or radiotherapy who have normal Hb levels at the start of treatment, as the literature has not shown a benefit with this approach. The addition of further supporting studies confirms our recommendation that the target Hb concentration following treatment with erythropoietic proteins should be 12-13 g/dL. Once this level is achieved, maintenance doses should be titrated individually. There is Level I evidence that dosing of erythropoietic proteins less frequently than three times per week is efficacious when used to treat chemotherapy-induced anaemia or prevent cancer anaemia, with studies supporting the use of epoetin alfa and epoetin beta weekly and darbepoetin alfa given every week or every 3 weeks. We do not recommend the use of higher than standard initial doses of erythropoietic proteins with the aim of producing higher haematological responses, due to the limited body of evidence available. There is Level I evidence that, within reasonable limits of body weight, fixed doses of erythropoietic proteins can be used to treat patients with chemotherapy-induced anaemia. This analysis confirms that there are no baseline predictive factors of response to erythropoietic proteins that can be routinely used in clinical practice if functional iron deficiency or vitamin deficiency is ruled out; a low serum erythropoietin (EPO) level (only in haematological malignancies) appears to be the only predictive factor to be verified in Level I studies. Further studies are needed to investigate the value of hepcidin, c-reactive protein, and other measures as predictive factors. In these updated guidelines, we explored a new question of whether oral or intravenous iron supplementation increases the response rate to erythropoietic proteins. We found no evidence of increased response with the addition of oral iron supplementation, but there is Level II evidence of improved response to erythropoietic proteins with the addition of intravenous iron. However, the doses and schedules for intravenous iron supplementation are not yet well defined, and further studies in this area are warranted. The two major goals of erythropoietic protein therapy are prevention or elimination of transfusions and improvement of QoL. The total body of evidence shows that red blood cell (RBC) transfusion requirements are reduced following treatment with erythropoietic proteins. This analysis also confirms that QoL is significantly improved in patients with chemotherapy-induced anaemia and in those with anaemia of chronic disease following erythropoietic protein therapy, with more robust evidence now available that QoL was improved in studies investigating early intervention in cases of chemotherapy- or radiotherapy-induced anaemia. There is only indirect evidence that patients with chemotherapy-induced anaemia or anaemia of chronic disease initially classified as non-responders to standard doses proceed to respond to treatment following a dose increase. None of the studies addressed the question in a prospective, randomised fashion, and so the Taskforce does not recommend dose escalation as a general approach in all patients who are not responding. There is still insufficient data to determine the effect on survival following treatment with erythropoietic proteins in conjunction with chemotherapy or radiotherapy. Our analysis of survival endpoints in studies involving patients receiving radio(chemo)therapy found that most studies were inconclusive, with no clear link between the use of erythropoietic proteins and survival. Likewise, we found no clear link between erythropoietic therapy and other endpoints such as local tumour control, time to progression, and progression-free survival. There is no evidence that pure red cell aplasia occurs in cancer patients following treatment with erythropoietic proteins, and the fear of this condition developing should not lead to erythropoietic proteins being withheld in patients with cancer. There is Level I evidence that the risk of thromboembolic events and hypertension are slightly elevated in patients with chemotherapy-induced anaemia receiving erythropoietic proteins. Additional trials are warranted, especially to define the optimal doses and schedules of intravenous iron supplementation during erythropoietic therapy. While our review did not address cost benefit evaluations in detail, the consensus is that studies taking into account all real determinants of cost and benefit need to be performed prospectively.

Chemotherapy-induced neutropenia is not only a major risk factor for infection-related morbidity and mortality, but is also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact on the success of treatment, particularly when treatment intent is either curative or to prolong survival. The incidence of severe or FN can be reduced by prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim, lenograstim or pegfilgrastim. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. While several academic groups have produced evidence-based clinical practice guidelines in an effort to standardise and optimise the management of FN, there remains a need for generally applicable, European-focused guidelines. To this end, we undertook a systematic literature review and formulated recommendations for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. We recommend that patient-related adverse risk factors such as elderly age (>or=65 years), be evaluated in the overall assessment of FN risk prior to administering each cycle of chemotherapy. In addition, when using a chemotherapy regimen associated with FN in >20% patients, prophylactic G-CSF is recommended. When using a chemotherapy regimen associated with FN in 10-20% patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Finally, studies have shown that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications, where indicated.

Anaemia is frequently diagnosed in patients with cancer, yet it is difficult to identify a single cause due to its multifactorial aetiology. We conducted a systematic literature review (1996-2003) to produce evidence-based guidelines on the use of erythropoietic proteins in anaemic patients with cancer (see ). Level I evidence exists for a positive impact of erythropoietic proteins on haemoglobin (Hb) levels when administered to patients with chemotherapy-induced anaemia or anaemia of chronic disease, when used to prevent cancer anaemia, in patients undergoing cancer surgery and following allogeneic bone marrow transplantation. The Hb level at which erythropoietic protein therapy should be initiated is difficult to determine as it varied between studies; a large number of Level I studies in patients with chemotherapy-induced anaemia or anaemia of chronic disease enrolled patients with a Hb concentration /=90 g/L) impact upon the response to erythropoietic proteins when used to treat chemotherapy-induced anaemia or prevent cancer anaemia. Evidence indicates that endogenous EPO concentration impacts on response in patients with lymphoproliferative malignancies, but is not a valid parameter in patients with solid tumours. There is Level I evidence that fixed doses of erythropoietic proteins can be used at the start of therapy to treat patients with chemotherapy-induced anaemia, but maintenance doses should be titrated individually. There is no evidence that pure red cell aplasia (PRCA) occurs following treatment with erythropoietic proteins in patients with chemotherapy-induced anaemia or when used prophylactically in patients with cancer. There is Level I evidence that the risk of thromboembolic events and hypertension are slightly elevated in patients with chemotherapy-induced anaemia receiving erythropoietic proteins. Level I evidence supports the effectiveness of erythropoietic proteins to prevenroteins to prevent anaemia in non-anaemic cancer patients receiving chemotherapy or radiotherapy or in those undergoing cancer surgery. However, these are non-licensed indications and we do not currently recommend the prophylactic use of erythropoietic proteins to prevent anaemia in patients who have normal Hb values at the start of treatment. Additional trials are warranted, especially on the issues of iron replacement and cost-effectiveness of erythropoietic protein therapy, as well as on tumour response/progression and survival.

Radiation-induced nausea and vomiting (RINV) affect the management and quality of life of cancer patients. Current guidelines for RINV prevention recommend prophylaxis with a 5-hydroxytryptamine (5-HT(3))-receptor antagonist for patients receiving moderately or highly emetogenic radiotherapy regimens. Randomised trials have compared such antagonists with conventional antiemetics, and have demonstrated their efficacy and safety. Special consideration is needed for antiemetic treatment in certain patient groups, particularly the elderly and those with renal or hepatic impairment. Radiation oncologists should be aware of the effect on antiemetic treatment of factors such as comorbid conditions (particularly cardiovascular disease), polypharmacy and drug-drug interactions, and choose the agent with the lowest potential for additional complications. The most appropriate antiemetic treatment to improve patient compliance and quality of life should ideally combine proven efficacy with uncomplicated administration and convenient dosing regimens.

Increasing age is not, in itself, a contraindication to cancer chemotherapy. Myelosuppression, however, a common adverse consequence of the administration of many standard-dose chemotherapy regimens to both young and elderly patients with cancer, increases with age. The risk of development of febrile neutropenia may contribute to a reluctance to administer chemotherapy in the elderly patient population. We conducted a detailed literature search (1992-2002) to derive evidence-based conclusions on the value of prophylactic colony-stimulating factor (CSF) administration in elderly patients receiving chemotherapy. Sufficient evidence allows us to affirm that prophylactic granulocyte colony-stimulating factor (G-CSF) reduces the incidence of chemotherapy-induced neutropenia, febrile neutropenia and infections in elderly patients receiving myelotoxic chemotherapy for non-Hodgkin's lymphoma (NHL), small-cell lung cancer (SCLC) or urothelial tumours. Lack of available trial data does not allow similar conclusions to be drawn for other cancers studied, but it is likely that similar benefits would accrue from the use of prophylactic G-CSF. There is insufficient evidence to extend this recommendation to include the use of granulocyte-macrophage colony-stimulating factor (GM-CSF). There are insufficient data available to allow the evaluation of the impact of prophylactic CSF on the incidence of toxic deaths in elderly patients with cancer and this is a crucial question for geriatric oncology practice. There is no evidence in elderly patients that the delivery of standard-dose chemotherapy on schedule improves efficacy measures. The data show that febrile neutropenic events are more likely to occur during the first and second cycles of chemotherapy, thus prophylactic measures should be considered early in the course of treatment. Furthermore, since systematic dose reduction can impact on outcome, primary prophylactic use of G-CSF for all elderly patients receiving curative myelotoxic chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or CHOP-like) is indicated and we suggest a risk-adapted strategy with primary prophylactic G-CSF administration in high-risk patients. Dose intensification, through dose interval reduction, facilitated by prophylactic G-CSF, improved survival in elderly patients with some specific diseases. There is a need for further well-designed studies to identify the elderly patients who will benefit most from prophylactic G-CSF. To achieve this, we strongly urge the design of and participation in further trials.

30 patients with advanced ovarian cancer, all platinum pretreated, were treated with an induction cycle of fotemustine. Maintenance therapy was given to 6 patients. No objective response was observed among the 21 evaluable patients. The main toxicities were gastrointestinal, with grade 3 nausea and vomiting reported in 40% of the patients, and haematological, with grade 4 leucopenia reported in 2 patients and grade 4 thrombocytopenia in 5 patients. Therefore, no role has been demonstrated in our cohort for the use of fotemustine, a nitrosourea, in pretreated ovarian cancer.

Advances in antiemetic therapy for chemotherapy-induced emesis have resulted in improved protection against symptoms occurring within 24 h of chemotherapy. However, the vomiting which tends to occur beyond 24 h after chemotherapy (delayed-phase vomiting) is still relatively poorly controlled by the currently available drugs, suggesting that more than one mechanism may mediate these symptoms. The standard antiemetic regimen currently recommended for prevention of chemotherapy-induced emesis includes a serotonin (5-HT(3)) antagonist and a corticosteroid. The neurokinin-1 (NK(1)) antagonist aprepitant represents a new class of antiemetic currently in clinical development. Using data obtained in 2 Phase II clinical trials of aprepitant in patients receiving chemotherapy based on the highly emetogenic chemotherapeutic agent cisplatin, we compared the time course of antiemetic effect of aprepitant, a 5-HT(3) antagonist, or a combination of both. Over the entire observation period (up to 7 days post-cisplatin), patients who received the NK(1) antagonist had a superior prevention of emesis. However, in the first 24 h after cisplatin, emesis occurred in fewer patients who received the 5-HT(3) antagonist than in patients who did not receive this class of drug. Furthermore, the majority of treatment failures in patients who received the NK(1) antagonist occurred within the first 8-12 h of chemotherapy, whereas the treatment failures in patients who received a 5-HT(3) antagonist were more evenly distributed over time. Patients who received both drugs had superior control of symptoms compared with patients who received one or the other. The difference in the time course of emesis blockade observed with two different classes of receptor antagonists provides substantial evidence for involvement of separate pathophysiological mechanisms in chemotherapy-induced vomiting. Serotonin mediates the early vomiting process that occurs within 8-12 h following cisplatin-based chemotherapy, after which time substance P acting at NK(1) receptors becomes the dominant mediator of vomiting

Patients with advanced malignancy are at an increased risk of cardiac arrhythmias, from their cancer and cardiotoxic treatments. Supportive care products co-administered should therefore not increase this risk. No clinically important cardiovascular effects are associated with the administration of granisetron over 30 s. To determine the effects of a rapid (1 s) injection of granisetron, 3 mg, on measures of cardiac repolarisation, a pilot study was performed in 17 patients undergoing moderately/highly emetogenic chemotherapy at two centres. All received dexamethasone, 8-12 mg, infused over 30 min, followed immediately by granisetron and then chemotherapy. Twelve-lead electrocardiograms (ECGs) performed before granisetron treatment, 2 h later and the following day (11 patients) showed no differences in QTc(end max), QTc(apex max) or QT-interval dispersion between baseline and subsequent measurements, and there were no significant secondary adverse events. On this basis, granisetron should be considered the first-choice antiemetic for patients at increased risk of cardiac complications.

Today, adjuvant 5-fluorouracil based therapy is known to significantly reduce the relapse rates and the risks of dying from resected colon cancer; chemotherapy approximately doubles overall survival of advanced colorectal cancer and second line treatment prolongs the survival of patients compared with best supportive care. At the molecular level a number of key genes are often mutated in cancer of the colon and some of these key regulators of apoptosis are discussed (p53 and bcl-2 family of proteins). Dihydropyrimidine dehydrogenase (DPD) activity may be a potential factor controlling fluorouracil (FU) responsiveness at the tumoral level and its importance is stressed. The rationale of combining FU with DPD inhibitors is fairly strong. Ethynyluracil, UFT and S1 pursue this strategy while capecitabine has another the rationale. Drug resistance should be at least partially overcome by combination chemotherapy (FU plus mitomycin, oxaliplatin, irinotecan) and combined modality (FU+RT) regimens. Improved surgical techniques and radiotherapy have substantially decreased local failure rates for rectal cancers. Finally, innovative treatment modalities such as anti-angiogenetic and antimetastatic agents, farnesyl transferase inhibitors, vaccine and gene therapy are in early clinical trials.

Docetaxel (Taxotere) has been studied at a dose of 100 mg/m2 i.v. as a one hour infusion every 3 weeks, in four phase II trials in patients with extensively pretreated ovarian cancer. A total of 340 patients were treated, including 256 patients in two separate EORTC (European Organization for Research and Treatment of Cancer) trials and 84 patients in two trials in the U.S.A. All patients had received prior cisplatin or carboplatin therapy and the treatment-free interval was less than 4 months in 155 patients. The overall response rate using conventional UICC criteria was 30% among 315 evaluable cases (95% confidence interval: 24-36%). Among 155 patients whose disease was most refractory (i.e. treatment-free interval was less than 4 months), the overall response rate was 28% (95% confidence interval: 19-36%). Response duration ranged from 4 to 17 months. Grade IV neutropenia was a common finding and fluid retention was observed. The incidence of febrile neutropenia ranged from 8 to 44% of patients with two deaths (i.e. 0.6% of the total treated) related to neutropenic sepsis. Docetaxel and paclitaxel (Taxol) have comparable activities in ovarian cancer. Ongoing studies with docetaxel include its use in patients as part of first-line therapy, as well as in patients refractory to paclitaxel. To prevent the development of fluid retention, these now involve the routine use of steroid prophylaxis. It is expected that docetaxel will prove to be an important addition to the drugs available for the treatment of ovarian cancer.

The efficacies of granisetron plus dexamethasone and granisetron alone in controlling nausea and vomiting during two consecutive cycles of moderately emetogenic chemotherapy given for up to 5 days were compared in a two-centre, randomised, double-blind, placebo-controlled crossover study. In all, 110 evaluable patients received either dexamethasone, 20 mg i.v., or matching placebo, plus open-label granisetron, 3 mg i.v., given on each chemotherapy day. At cycle 2, patients crossed over to the alternative treatment; 72 patients completed the crossover. In these 72 patients, the complete response rates over 24 h for granisetron plus dexamethasone and granisetron plus placebo in cycle 1 were 87% and 70% (ns), respectively. In cycle 2 the complete response rates over 24 h were 73% and 62% (ns). Combining the two cycles, the complete response rates over 24 h were 80.6% (granisetron plus dexamethasone) and 65.3% (granisetron plus placebo; P = 0.015). Granisetron plus dexamethasone was significantly more effective in terms of times to less than complete response (P = 0.041), to first episode of moderate/severe nausea (P = 0.04), to first episode of vomiting (0.03) and to use of rescue medication (P = 0.02). Adverse events tended to be minor, with asthenia and insomnia the most common. Of those patients who expressed a preference, 67% preferred granisetron plus dexamethasone (P < 0.05). A single dose of dexamethasone added to granisetron thus enhances the efficacy of granisetron alone in preventing nausea and vomiting after moderately emetogenic chemotherapy.

The aim of this study was to examine the early and late complications rate of central venous access ports connected to the Groshong catheter for long-term chemotherapy delivering. All patients suffering from a neoplastic disease, who required long-term chemotherapy and underwent insertion of implantable ports during a 21-month period (1 October 1994-30 June 1996) were prospectively studied. A single type of port was used, constructed of titanium and silicone rubber (Dome Port, Bard Inc., Salt Lake City, U.S.A), connected to an 8 F silastic Groshong catheter tubing (Bard Inc.). A team of different operators (two general surgeons, one interventional radiologist and four anaesthesiologists) was involved in inserting the port. All devices were placed in the operating room under fluoroscopic control. A central venous access form was filled in by the operator after the procedure and all ports were followed prospectively for device-related and overall complications. Data from the follow-up of these patients were entered in the form and collected in a database. Follow-up continued until the device was removed, the patient died or the study was closed. 178 devices, comprising a total of 32,089 days in situ, were placed in 175 patients. Three patients received a second device after removal of the first. Adequate follow-up was obtained in all cases (median 180 days, range 4-559). 138 devices (77.5%) were still in situ when the study was closed. Early complications included six pneumothoraxes, three arterial punctures and two revisions for port and/or catheter malfunction (overall early complications in 8 patients). Late complications included 3 cases (1.68% of devices) of catheter rupture and embolisation (0.093 episodes/1000 days of use), 2 cases (1.12% of devices) of venous thrombosis (0.062 episodes/1000 days of use), 1 case (0.56% of devices) of pocket infection (0.031 episodes/1000 days of use), and 4 cases (2.24% of devices) of port-related bacteraemias (0.124 episodes/1000 days of use). Infections were caused by coagulase-negative Staphylococcus aureus (4 cases) and Bacillus subtilis (1 case); they required port removal in 3 out of 5 cases. This study represents the largest published series of patients with totally implantable access ports connected to Groshong catheters; this device is a good option for long-term access to central veins and delivery of chemotherapeutic regimens, including continuous intravenous infusions. The low incidence of major complications related to implantation and management of these devices support increased use in oncology patients.

Docetaxel has been evaluated in 293 patients with advanced ovarian cancer in three phase II trials. All patients had previously received cisplatin and/or carboplatin as first-line treatment. In all three studies, treatment comprised docetaxel 100 mg/m2 as a 1 h intravenous infusion every 3 weeks, without premedication for hypersensitivity reactions or emesis. To date, 200 patients are evaluable for response. Of these, 63 patients achieved complete or partial response, giving an overall response rate of 31.5% (95% confidence interval 24-39%) for all evaluable patients, or 21.5% for all patients entered in the studies. Of the 57 patients whose disease had progressed either during previous therapy or within 4 months of discontinuing previous therapy, 13 (23%) responded to docetaxel (EORTC data). Major adverse effects of docetaxel observed in approximately half the patients (particularly those who received more than four courses) included skin reactions and fluid retention. Grade III or IV neutropenia was common but short-lived. Severe acute hypersensitivity reactions occurred in approximately 5% of patients. Docetaxel now warrants evaluation as part of first-line therapy. Studies aimed at reducing the incidence of fluid retention and skin reactions with docetaxel are ongoing.

Docetaxel has been evaluated in six phase I studies involving a total of 234 patients with a wide variety of tumour types (50% had breast or ovarian cancer). The aims of these studies were to determine the optimal dosage schedule of docetaxel for use in subsequent phase II studies, and to characterise the pharmacokinetic and tolerability profiles of docetaxel. Intravenous (i.v.) doses of docetaxel (5-115 mg/m2) were administered in various treatment schedules for a total of 790 courses. Cycles were repeated every 2-3 weeks. Dose-dependent neutropenia was the major dose-limiting adverse effect of docetaxel. Other adverse events reported included hypersensitivity, fluid retention, skin reactions, asthenia and alopecia. Anaphylactoid reactions occurred rarely. No abnormal cardiac activity was detected, and neurological adverse events were mild. Docetaxel 100 mg/m2 administered as a 1 h i.v. infusion every 3 weeks combined acceptable tolerability with complete neutropenic recovery. This dosage schedule was thus considered to be optimal for further investigation in phase II studies.

Taxotere (TER) and taxol (TA) are new antitumour agents currently undergoing clinical evaluation. We studied the antineoplastic effects of these agents (final concentrations: 4.0, 0.4, 0.04 mumol/l) on the in vitro proliferation of clonogenic cells from freshly explanted human tumours using a capillary soft agar cloning system. We also compared the activity of these new compounds to conventional antineoplastic agents (bleomycin, cisplatin, dacarbazine, doxorubicin, etoposide, 5-fluorouracil, vinblastine, interferon-alpha 2). Using a 21-28-day continuous drug exposure, 54/81 specimens (67%) were evaluable for comparisons, and using a 1-h drug exposure followed by 21-28 days incubation, 50/80 specimens (63%) were similarly evaluable. With both schedules, TA and TER showed concentration-related antitumour activity. At 0.4 mumol/l, median colony survival was 0.61 x control (range 0.09-0.96) for TA and 0.51 x control (0.15-0.81) for TER in the 1-h incubation (P = 0.0002). Median colony formation was also reduced significantly more by TER as compared to TA in the long-term incubation schedule. Statistical analysis indicated that TER but not TA was significantly more active than cisplatin (P = 0.02), doxorubicin (P = 0.01), 5-fluorouracil (P = 0.01) and interferon-alpha 2 (P = 0.01). We conclude that TER and TA are more active against in vitro tumour colony formation from freshly explanted human tumours. TER appears to be slightly more active than taxol and promises to be active against tumours resistant to conventional antineoplastics.

This paper reviews recent developments in the systemic treatment of advanced malignant melanoma. In the introduction emphasis is given to prevention and early detection of this disease. Metastatic malignant melanoma patients have a median survival of less than 1 year in the most favourable situation. Adjuvant chemotherapeutic treatment after initial surgery has not had an impact on prognosis, while immunological manipulations with interferon alfa or other agents may prove beneficial after primary surgery. In advanced disease which cannot be palliated by surgery, many approaches are under investigation. Modulation of the patient's immune response can be achieved with vaccines, monoclonal antibodies, interleukin-2 and interferons, as single agents or in combination between themselves or with peripheral blood mononuclear cells or with tumour infiltrating lymphocytes or even with chemotherapy. Immunological approaches yield a 20-30% response rate, with some possibly long-term responses. Chemotherapeutic agents have a 10-30% response rate, which is usually of short duration. Combinations of chemotherapeutic agents can increase the response rate to 50%, but an impact on ultimate survival seems unlikely. Randomised studies have shown that modulation of chemotherapy with interferon or tamoxifen improves response rates. Clinicians should be encouraged to enter their patients with malignant melanoma in therapeutic trials.

Within the EC approximately one million cases of cancer are diagnosed every year. At present, more than 55% of cancers occur in subjects aged over 65 years. There has been little clinical attention to the problem of neoplasia in the elderly. They are not receiving the same standard of specialised oncological care as younger patients. Other diseases (co-morbidity conditions) associated with cancer, and influencing its treatment and outcomes are not being properly considered. Information on surgery, radiotherapy and chemotherapy in younger patients exists for all cancers and could be adapted for the elderly. Controversial aspects of neoplasia in the elderly concern the intensity of chemotherapy, extent of surgery and the relative roles of specialised cancer centres, community hospitals and primary care providers. Future research should aim to replace subjective opinions on presence of frailty with objective instruments such as the multidimensional geriatric assessment scale. New trials could then seek to improve treatment in well-defined populations in terms of both efficacy and quality of life. Funding priorities should firstly consider that clinical trials for tumours in the elderly must be organised from cancer institutes and specialised referral centres in collaboration with geriatricians, primary care and community hospital physicians. Continuing education of doctors should be reported. A document such as this with appropriate modifications might be used as an initial message on neoplasia in the elderly to be published for information to clinicians and the public throughout Europe. Specific measures of quality assurance need financial support to evaluate the improvements in patterns of care. The 10 points of the 'Europe Against Cancer Guidelines' need reemphasising.

46 eligible patients with either anaplastic astrocytoma (AA) or glioblastoma (GBM) and clinical and computed-tomography-confirmed relapse following primary surgery and radiotherapy received oral tauromustine 130 mg/m2 every 5 weeks. A prospective design allowed for concurrent assessment of both clinical and radiological responses and drug toxicity. 41% of patients improved clinically whilst 46% improved radiologically with 3 complete, 7 partial and 7 minimal responses (WHO criteria). Toxicity included grade III or IV gastrointestinal side-effects (15%), grade III or IV leukopenia (24%) and grade III and IV thrombocytopenia (44%). In 9 clinically responding patients, haematological toxicity led to discontinuation of treatment. All patients were followed-up until death and second-line chemotherapy was not used. Median post-treatment survival was 26 weeks for patients with GBM and 57 weeks for patients with AA. Overall 2-year survival rate was 69% for AA and 23% for GBM. Tauromustine given at the time of relapse has demonstrable antitumour activity in patients not previously treated with chemotherapy.

Combinations of dopamine antagonists or high-dose metoclopramide with steroids can provide complete control of chemotherapy-related nausea and vomiting in up to 60-70% of patients undergoing high-dose cisplatin-based chemotherapy. High-dose metoclopramide probably acts as a 5-HT3 receptor antagonist, but because of its dopamine-receptor antagonism it is the cause of extrapyramidal side-effects. These compounds, and the agents used in combination with them, tend to cause sedation, an undesirable effect in the outpatient setting. Specific 5-HT3 receptor antagonists (ondansetron, granisetron, tropisetron) give a similar control of chemotherapy related nausea and vomiting, with minimum side-effects. These drugs can cause headaches and constipation and some have been related to transient liver enzyme abnormalities in cancer patients; however, disease and chemotherapy might also be the cause of the enzyme anomalies. Combinations of 5-HT3 receptor antagonists with steroids may provide a very high degree of protection.