Anders Bonde Jensen

Phase III Randomized Study Comparing Docetaxel Plus Trastuzumab With Vinorelbine Plus Trastuzumab As First-Line Therapy of Metastatic or Locally Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: The HERNATA Study

PURPOSE To evaluate docetaxel or vinorelbine, both with trastuzumab, as first-line therapy of human epidermal growth factor receptor 2-positive advanced breast cancer. PATIENTS AND METHODS Patients naive to chemotherapy for advanced disease were randomly assigned to docetaxel 100 mg/m(2) day 1 or vinorelbine 30 to 35 mg/m(2) on days 1 and 8, both combined with trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance dose) on day 1 every 3 weeks. The primary end point was time to progression (TTP). RESULTS A total of 143 patients were randomly allocated to docetaxel, and 141 patients were assigned to vinorelbine. The median TTP for docetaxel and vinorelbine respectively was 12.4 months versus 15.3 months (hazard ratio [HR] = 0.94; 95% CI, 0.71 to 1.25; P = .67), median overall survival was 35.7 months versus 38.8 months (HR = 1.01; 95% CI, 0.71 to 1.42; P = .98), and the 1-year survival rate was 88% in both arms. Median time to treatment failure for study chemotherapy was 5.6 months versus 7.7 months (HR = 0.50; 95% CI, 0.38 to 0.64; P < .0001). The investigator-assessed overall response rate among 241 patients with measurable disease were 59.3% in both arms. More patients in the docetaxel arm discontinued therapy due to toxicity (P < .001). Significantly more treatment-related grade 3 to 4 febrile neutropenia (36.0% v 10.1%), leucopenia (40.3% v 21.0%), infection 25.1% v 13.0%), fever (4.3% v 0%), neuropathy (30.9% v 3.6%), nail changes (7.9% v 0.7%), and edema (6.5% v 0%) were reported with docetaxel. CONCLUSION The study failed to demonstrate superiority of any drug in terms of efficacy, but the vinorelbine combination had significantly fewer adverse effects and should be considered as an alternative first-line option.

Late effects of breast cancer treatment and potentials for rehabilitation

Abstract Background. Breast cancer is the most frequent malignant disease among women world wide. Survival has been improving leading to an increasing number of breast cancer survivors, in the US estimated to about 2.6 million. Material and methods. The literature was reviewed with focus on data from the Nordic countries. Results. Local therapies such as breast cancer surgery and radiotherapy may cause persistent pain in the breast area, arm, and shoulder reported by 30–50% of patients after three to five years, lymphedema in 15–25% of patients, and restrictions of arm and shoulder movement in 35%. Physiotherapy is the standard treatment for the latter while no pain intervention trials have been published. Chemotherapy may cause infertility and premature menopause, resulting in vasomotor symptoms, sexual dysfunction, and osteoporosis, which are similar to the side effects of endocrine treatment in postmenopausal women. Awareness of cardiotoxicity is needed since anthracyclines, trastuzumab, and radiotherapy can damage the heart. Breast cancer survivors have an increased risk of a major depression and far from all receive adequate anti-depressive treatment. Other psychological symptoms include fear of recurrence, sleep disturbances, cognitive problems, fatigue, and sexual problems. Discussion. To improve rehabilitation, specific goals have to be formulated into national guidelines and high priority directed towards research into developing and testing new interventions for alleviating symptoms and side effects experienced by breast cancer survivors.

Influence of Late Side-Effects Upon Daily Life After Radiotherapy for Laryngeal and Pharyngeal Cancer

The influence on daily life from long-term side-effects was studied in patients treated more than 5 years ago with radiotherapy for laryngeal and pharyngeal cancer. Forty-six patients were asked to participate in telephone interviews and 44 participated. Only a minority (10%) stated serious problems related to the treatment. Problems related to the voice and severe xerostomia were especially mentioned. Half of the patients treated for pharyngeal cancer, complained of xerostomia and had occasionally a feeling of being handicapped. Social relations were impaired in 10% of the patients and 10% had retired due to their cancer or therapy related side-effects. It is concluded that radiotherapy seems to be a well tolerated treatment with relatively little impairment of the daily life in patients with laryngeal cancer. In patients with pharyngeal cancer, xerostomia is a major problem, which often persists more than 5 years after treatment.

The Cathepsin K Inhibitor Odanacatib Suppresses Bone Resorption in Women With Breast Cancer and Established Bone Metastases: Results of a 4-Week, Double-Blind, Randomized, Controlled Trial

BACKGROUND Metastatic bone disease (MBD) is a frequent complication in patients with breast cancer and is associated with significant morbidity. This study assessed the pharmacokinetics, efficacy, and safety of odanacatib, a selective Cat K inhibitor, in reducing markers of bone resorption in women with breast cancer and MBD. PATIENTS AND METHODS Women with breast cancer and MBD were randomized 2:1 (double-blind) to oral odanacatib 5 mg daily for 4 weeks or intravenous (I.V.) zoledronic acid (ZA) 4 mg given once at study initiation. Plasma samples were collected for pharmacokinetic analysis. Bone resorption was assessed by measuring urinary N-telopeptide of type I collagen corrected for creatinine (uNTx; primary objective, pmol BCE/µmol creatinine). Adverse events (AEs) were monitored throughout the 4-week study and up to 14 days after last dose. RESULTS A total of 43 patients (mean age, 60 years) received odanacatib (n = 29) or ZA (n = 14); 40 patients completed 4 weeks of treatment. The mean percent change in uNTx values at week 4 was -77% (95% CI, -82 to -71; odanacatib) and -73% (95% CI, -80 to -62; ZA). Mean (standard deviation) plasma concentration of odanacatib was 511.7 (202.9) nM; the range was 63.7-844.8 nM. The most common AEs were nausea, vomiting, headache, and bone pain, which were generally not attributed to study drug. CONCLUSION Odanacatib suppressed uNTx similarly to ZA after 4 weeks of treatment in women with breast cancer and MBD. Odanacatib was generally safe and well tolerated. These results suggest that Cat K inhibition is a potentially important, novel therapeutic approach for treating MBD.

No indications of cognitive side-effects in a prospective study of breast cancer patients receiving adjuvant chemotherapy

Objective: A number of cross‐sectional studies have reported reduced cognitive function in cancer patients receiving chemotherapy compared with other cancer patients and healthy controls, suggesting that chemotherapy could be associated with cognitive side‐effects. Recently published prospective studies question this hypothesis, but it is still unclear whether cancer patients should regard cognitive problems as a potential risk when receiving chemotherapy.

How traumatic is breast cancer? Post-traumatic stress symptoms (PTSS) and risk factors for severe PTSS at 3 and 15 months after surgery in a nationwide cohort of Danish women treated for primary breast cancer.

Background:The literature shows considerable between-study variation in the prevalence of post-traumatic stress symptoms (PTSS) among women with breast cancer. Our aim was, therefore, to explore the prevalence of and risk factors for cancer-related PTSS in a nationwide inception cohort of women treated for primary breast cancer.Methods:In all, 68% of all Danish women receiving surgery for primary breast cancer between October 2001 and March 2004 completed a questionnaire at 3 months post surgery (n=3343), which included the impact of event scale (IES). In all, 94% of the disease-free women also completed a follow-up questionnaire at 15 months post surgery. Data on pre-cancer demographic, socioeconomic, and psychiatric status were obtained from national registries. The Danish Breast Cancer Cooperative Group and surgical departments provided information on disease variables, treatment, and comorbidity.Results:At 3 months post surgery, 20.1% had IES total scores suggesting severe PTSS (⩾35), compared with 14.3% at 15 months. In all, 48% with severe PTSS at 3 months also had scores above the cutoff at 15 months. Main predictors of severe PTSS at 15 months were low social status, previous physical and mental illness, axillary lymph node involvement (>3), and reduced physical functioning (PF) at 3 months.Conclusion:The results confirm that receiving a breast cancer diagnosis can be a significant traumatic experience, and that many women experience persistent cancer-related PTSS. Low social status, poor health status, low levels of PF, and disease severity were found to be risk factors for severe PTSS.

Prevalence, socio-demographic and clinical predictors of post-diagnostic utilisation of different types of complementary and alternative medicine (CAM) in a nationwide cohort of Danish women treated for primary breast cancer

AIM This study investigated the prevalence and predictors of use of complementary and alternative medicine (CAM) in a nationwide inception cohort of Danish women treated for early-stage breast cancer as well as differences in user patterns for individual types of CAM. METHODS Use of CAM since the time of diagnosis was assessed 12-16 weeks post-surgery for the 3343 women (age 18-70) included in the study (response rate: 68%). Socio-demographic and clinical variables were obtained from national longitudinal registries. RESULTS 40.1% of the women had used one or more types of CAM. Users were younger than non-users. Age adjusted analyses showed that CAM users were characterised by absence of comorbidity, higher educational level, higher personal income, higher social status, being divorced/separated and living in the metropolitan area of Copenhagen. Multivariate analyses revealed that chemotherapy was the only clinical and treatment-related predictor of CAM use, and that CAM users were more likely to be of normal weight and non-smokers. Of CAM users, 33.7% believed that CAM would have a positive influence upon their breast cancer. Different characteristics distinguished users of individual types of CAM. CONCLUSION The results of this first nationwide study of utilisation of CAM in breast cancer show that CAM users are healthier and more likely to have higher socio-economic status than non-users. Different user patterns for individual types of CAM may be overlooked, when different types of CAM are treated as one homogeneous category.

Chemotherapy-Induced Nausea, Vomiting, and Fatigue – the Role of Individual Differences Related to Sensory Perception and Autonomic Reactivity

Background: In spite of antiemetics, postchemotherapy side effects continue to be common and may affect compliance to cancer treatment. Among the known factors associated with increased symptom severity are: younger age, treatment toxicity, expected severity, and distress, but little is still known about the role of other factors. The aim of our study was to investigate the role of individual differences related to sensory perception for posttreatment side effects. Methods: Hundred and twenty-five women receiving adjuvant chemotherapy for breast cancer completed measures of absorption, autonomic perception, somatosensory amplification, trait anxiety, and expected severity at baseline. Pretreatment distress and posttreatment nausea, vomiting, and fatigue were assessed at the 1st, 4th, 6th and last cycles of chemotherapy. Results: While univariate analyses showed several factors to be associated with side effects, only absorption and pretreatment distress remained independent predictors of nausea and fatigue when controlling for the remaining factors. Posttreatment vomiting was only predicted by expected severity of vomiting. Conclusion: Chemotherapy-induced side effects are related to increased autonomic nervous system activity, and absorption has been associated with increased autonomic nervous system reactivity to stress. The results suggest that individuals with high absorption may be at greater risk for developing side effects. Improved precision in identifying patients at risk of experiencing more severe side effects after cancer treatment will increase the ability to target treatments aimed at reducing these side effects.

Congruence between preferred and actual place of care and death among Danish cancer patients.

Background: Meeting patient’s preferences is an important outcome in palliative care. No Scandinavian study has reported systematically collected preferences from patients regarding place of care (POC) and place of death (POD). The extent of possible incongruence between patients’ preferences and reality remains unknown. Aim: The aim of this study was to describe patients’ preferred POC and POD and changes in preferences over time and to evaluate congruence between preferences and reality. Furthermore, the aim was to search for predictive factors regarding patients’ wishes and fulfilment of these. Method: This is a prospective interview and questionnaire study. Setting/participants: The study was conducted in the former Aarhus County, Denmark and 96 end-stage cancer patients participated. Results: Of the patients, who stated a preference, 84% preferred home care and 71% preferred home death. A positive association between living with a partner and both wishing for home care and home death was observed (prevalence ratio (PR): 1.66 (95% confidence intervals (CI): 1.07, 2.58), p = 0.02 and PR: 2.33 (95% CI: 1.14, 4.77), p = 0.02, respectively). Marked changes in preferences were observed. Overall, preferences were met for approximately half of the patients, although kappa values were low (κ=0.132 for POC and κ=0.034 for POD).We found a significant association between being cared for in the preferred place and having contact with a palliative care team (PR: 2.01 (95% CI: 1.02, 3.98), p = 0.045). Conclusion: Regular discussions with patients on this subject are needed. Social and professional support is of importance in meeting patients’ preferences. Larger scaled studies and research focusing on meeting patients’ preferences are needed.

Cancer rehabilitation: Psychosocial rehabilitation needs after discharge from hospital?: A qualitative interview study

Objective. This study explores former cancer patients’ psychosocial rehabilitation needs after hospital discharge. Method. Three focus-group interviews with 15 patients. Results. Five main areas were identified: (1) Need for continuous support and information about rehabilitation opportunities; (2) Support to the family; (3) Psychological help also addressing fear of relapse of cancer; (4) Needs for social support; (5) Needs pertaining to how friends and acquaintances relate to the patients. Conclusion. Each of these aspects should be carefully considered for each patient, preferably by one assigned healthcare provider. Fear of cancer relapse prevails among the patients, the family and the social network and it is important in relation to psychosocial rehabilitation.