Five-year follow-up results of aerobic and impact training on bone mineral density in early breast cancer patients.

A 12-month exercise program reversibly prevented hip bone loss in premenopausal women with early breast cancer. The bone-protective effect was maintained for 2 years after the end of the program but was lost thereafter. PURPOSE: Breast cancer survivors are at an increased risk for osteoporosis and fracture. This 5-year follow-up of a randomized impact exercise intervention trial evaluated the maintenance of training effects on bone among breast cancer patients. METHODS: Five hundred seventy-three early breast cancer patients aged 35-68 years and treated with adjuvant therapy were allocated into a 12-month exercise program or a control group. Four hundred forty-four patients (77%) were included in the 5-year analysis. The exercise intervention comprised weekly supervised step aerobics, circuit exercises, and home training. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry. Physical activity was estimated in metabolic equivalent (MET) hours per week and physical performance assessed by 2-km walking and figure-8 running tests. RESULTS: In premenopausal patients, the 12-month exercise program maintained femoral neck (FN) and total hip (TH) aBMD for 3 years, but the protective effect was lost thereafter. The mean FN aBMD change in the exercise and control groups was - 0.2% and - 1.5% 1 year, - 1.1% and - 2.1% 3 years and - 3.3% versus - 2.4% 5 years after the beginning of the intervention, respectively. Lumbar spine (LS) bone loss was not prevented in premenopausal women and no training effects on aBMD were seen in postmenopausal women. The main confounding element of the study was the unexpected rise in physical activity among patients in the control group. The physical performance improved among premenopausal women in the exercise group compared with the controls. CONCLUSION: The 12-month exercise program prevented FN and TH bone loss in premenopausal breast cancer patients for 3 years. The bone-protective effect was reversible and lost thereafter.

Non-curative treatment of patients with oral tongue squamous-cell carcinoma.

PURPOSE: Late-stage OTSCC is associated with poor overall survival (OS). Non-curative treatment approach aims to improve quality of life and prolong survival of patients deemed incurable. The purpose of this study was to investigate the used non-curative treatment modalities for OTSSC and patient survival. METHODS: All patients diagnosed with OTSCC and treated with non-curative intent at the HUS Helsinki University Hospital (Helsinki, Finland) during the 12-year period of 2005-2016 were included. Survival analysis after the non-curative treatment decision was conducted using the Kaplan-Meier method in this population-based study. RESULTS: Eighty-two patients were identified. A non-curative treatment decision was made at presentation without any previous treatment in 26 patients (7% of all patients diagnosed with OTSCC during the study period). Palliative radiotherapy was administered to 24% of all patients. The average survival time after the non-curative treatment decision was 3.7 months (median 2 and range 0-26). CONCLUSIONS: Due to the short mean survival time after decision for treatment with non-curative intent, and the notable symptom burden in this patient population, a prompt initiation of all non-curative measures is warranted.

Marked deterioration in the quality of life of patients with idiopathic pulmonary fibrosis during the last two years of life.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic disease with a high symptom burden and poor survival that influences patients' health-related quality of life (HRQOL). We aimed to evaluate IPF patients' symptoms and HRQOL in a well-documented clinical cohort during their last two years of life. METHODS: In April 2015, we sent the Modified Medical Research Council Dyspnea Scale (MMRC), the modified Edmonton Symptom Assessment Scale (ESAS) and a self-rating HRQOL questionnaire (RAND-36) to 300 IPF patients, of which 247 (82%) responded. Thereafter, follow-up questionnaires were sent every six months for two years. RESULTS: Ninety-two patients died by August 2017. Among these patients, HRQOL was found to be considerably low already two years before death. The most prominent declines in HRQOL occurred in physical function, vitality, emotional role and social functioning (p < 0.001). The proportion of patients with MMRC scores ≥3 increased near death. Breathlessness and fatigue were the most severe symptoms. Symptom severity for the following symptoms increased significantly and reached the highest mean scores during the last six months of life (numeric rating scale/standard deviation): breathlessness (7.1/2.8), tiredness (7.0/2.3), dry mouth (6.0/3.0), cough (5.8/2.9), and pain with movement (5.0/3.5). CONCLUSIONS: To our knowledge this is the first study demonstrating, that IPF patients experience remarkably low HRQOL already two years before death, especially regarding physical role. In addition, they suffer from severe breathlessness and fatigue. Furthermore, physical, social and emotional wellbeing deteriorate, and symptom burden increases near death. Regular symptom and HRQOL measurements are essential to assess palliative care needs in patients with IPF.

End-of-life care pathway of head and neck cancer patients: single-institution experience.

BACKGROUND: Studies on palliative care of head and neck cancer (HNC) patients are scarce although the affected patient population is quite large. OBJECTIVE: To evaluate the role of a specialised palliative-care pathway of HNC patients. PATIENTS AND METHODS: Data on all HNC patients who were treated at the Helsinki University Hospital Palliative Care Center during 1 year were retrospectively reviewed. The analysis comprised 60 patients (49 males; mean age 67 years; range 28-88). All patients had a minimum follow-up of 1 year or until death. RESULTS: Fifty-nine (98%) out of the 60 patients died during the follow-up period. Median survival after diagnosis was 11 months (range 3 weeks-11.9 years) and after withholding disease-specific therapies 3 months (range 0-16). Thirty-three (55%) patients received palliative radiotherapy, 27 (45%) had PEG tube and 17 (28%) tracheostomy. Thirty-seven (66%) patients visited an emergency department (ED) (median 1.3 visits; range 0-6) and 21 (35%) were hospitalised at the university hospital during the palliative period. The most common severe complications were infection (also the most common reason for ED visits and hospitalisation), bleeding (four massive airway bleedings with one death), delirium and airway obstruction (one emergency tracheostomy). Twelve (35%) out of the 34 patients who were referred to specialised home care died at home as compared with three (12%) out of the 26 patients not supported by a specialised home-care team. CONCLUSIONS: Severe complications leading to an emergency unit visit and hospitalisation are common among HNC patients in their relatively short palliative period reflecting the need for early-integrated palliative care. Collaboration with a specialised palliative home-care team seems to increase end-of-life care at home.

The functional capacity and quality of life of women with advanced breast cancer.

BACKGROUND: The rehabilitation needs of patients with metastatic breast cancer (MBC) are poorly studied. The primary aim of the study was to evaluate the functional capacity of women with MBC and quality of life (QoL). METHODS: The present study is an open, non-randomized, prospective cross-sectional observation study. The functional capacity of 128 MBC patients with ongoing cancer treatments, were studied in Helsinki University Hospital (HUS): Peak expiratory flow (PEF), dynamic and static balance, 6 minute walking distance (6MWD), 10 meter walking, sit-to-stand test, repeated squat, grip strength, shoulder movement, pain, and QoL by Beck's depression scale (BDI), health assessment questionnaire (HAQ), RAND SF-36 and EORTC QLQ-30 items. RESULTS: The walking capacity was compromised in half and the strength of the lower extremities in one-third of the patients. PEF was below the normal reference in 55 %, static balance in 62 % and dynamic balance in 73 % (≤60 year olds) and 81 % (≥61 year olds). The grip power was lowered in 44/30 % of the patients (right/left) and the shoulder movement was restricted in 30 %. Some disability in physical functioning experienced 55 % (HAQ) and 37 % felt depressive (BDI). The QoL (RAND SF-36) was poor especially in the field of physical, role and social functioning and bodily pain (<0.001). Pain, depression, and a poor 6MWD results independently determined the physical component of QoL (p < 0.001). CONCLUSIONS: The functional capacity of patients with MBC was significantly lowered. This, in association with distressing symptoms like pain and depression causes a vicious circle further leading to functional disabilities and impaired QoL.

End-of-life care of patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with median survival from 2 to 7 years. Palliative care is an important part of patients´ care as lung transplantation is not an option for the majority of patients. The aim of this study was to describe treatment practices, decision-making and symptoms during end-of-life care of IPF patients. METHODS: We identified 59 deceased patients from a national prospective IPF cohort study (FinnishIPF) and analyzed retrospectively their health care documentation during the 6 months that preceded death. RESULTS: Hospital was the place of death for 47 patients (80 %). A majority of the patients (93 %) were hospitalized for a mean of 30 days (range 1-96 days) during the last 6 months of their life. Altogether, patients spent 15 % of their last 6 months of life in a hospital. End-of-life decisions and do not resuscitate (DNR) orders were made for 19 (32 %) and 34 (57 %) of the patients, respectively, and 22 (42 %) of these decisions were made ≤ 3 days prior to death. During the final hospital stay, antibiotics were given to 79 % and non-invasive ventilation to 36 % of patients. During the last 24 h of life, radiologic imaging or laboratory tests were taken in 19 % and 53 % of the hospitalized patients, respectively. These tests and life prolonging therapies were more common in tertiary hospitals compared to other places of death. Dyspnea (66 %) and pain (31 %) were the most common symptoms recorded. Opioids were prescribed to 71 % of the patients during the last week before death. CONCLUSIONS: The majority of IPF patients died in a hospital with ongoing life-prolonging procedures until death. The frequent use of opioids is an indicator of an intention to relieve symptoms, but end-of-life decisions were still made very late. Early integrated palliative care with advance care plan could improve the end-of-life care of dying IPF patients.

Early-stage breast cancer is not associated with the risk of marital dissolution in a large prospective study of women.

BACKGROUND: As breast cancer and its treatment are likely to interfere with traditional expectations of womanhood, it may affect marital stability. METHODS: The risk of marital dissolution was analysed with respect to diagnosis of early-stage (T1-4N0-3M0) breast cancer in a cohort of 134 435 married Finnish women followed for a median of 17.0 married years. Age, socioeconomic status, education, number of children, duration of marriage and earlier marriages were taken into account and the effects of surgery, chemotherapy, radiotherapy and endocrine therapy were analysed separately. RESULTS: Women with a diagnosis of early-stage breast cancer did not show increase in marital dissolution (hazard ratio=0.96, 95% confidence interval=0.79-1.17). Neither the type of surgical procedure nor any of the oncologic treatments was associated with an increase in the risk of divorce. CONCLUSIONS: Any evidence of excess risk of marital breakdown after the diagnosis of early-stage breast cancer and its treatment was not demonstrated.

Health-related quality of life in colorectal cancer.

AIM: As a consequence of the improved survival of patients and of cost-effectiveness requirements for new treatments, health-related quality of life (HRQoL) issues have gained increasing attention in colorectal cancer (CRC). This cross-sectional study assesses HRQoL in several health states of CRC and explores factors influencing HRQoL. METHOD: Five hundred and eight Finnish CRC patients (aged 26-96 years; colon cancer 56%; women 47%) assessed their HRQoL using generic 15D and EQ-5D and cancer-specific EORTC QLQ-C30 questionnaires. Patients were divided into five groups: primary treatment, rehabilitation, remission, metastatic disease and palliative care. The patients' HRQoL was compared with population reference values. Multivariate modelling was used to find factors associated with HRQoL scores. RESULTS: The HRQoL of CRC patients is fairly good and comparable with that of the standardized general population except for those under palliative care. The mean 15D score of patients in the primary treatment group was 0.889 (95% CI 0.869-0.914), in rehabilitation 0.877 (0.855-0.907), in remission 0.886 (0.875-0.903), in metastatic disease 0.860 (0.844-0.878) and in palliative care 0.758 (0.716-0.808). The respective EQ-5D scores were 0.760 (0.699-0.823), 0.835 (0.777-0.881), 0.850 (0.828-0.882), 0.820 (0.783-0.858) and 0.643 (0.546-0.747). Multivariate analysis showed that fatigue, pain, age and financial difficulties had a marked negative impact on HRQoL. CONCLUSION: The mean HRQoL scores of CRC patients varied considerably depending on the HRQoL instrument used, but remained surprisingly good up to the palliative stage. In addition to age- and cancer-related symptoms, financial difficulties also had a clear negative impact on HRQoL, which needs to be taken into consideration when supporting patient HRQoL.

Effect of exercise on bone structural traits, physical performance and body composition in breast cancer patients--a 12-month RCT.

In this 12-month RCT, we examined whether aerobic impact exercise training (3x/week) could facilitate breast cancer survivors' recovery by enhancing their bone structural strength, physical performance and body composition. After the adjuvant chemo- and/ or radiotherapy, 86 patients were randomly assigned into the training or control group. Structural bone traits were assessed with pQCT at the tibia and with DXA at the femoral neck. Agility (figure-8 running), jump force and power (force platform), grip strength and cardiovascular fitness (2-km walk test) were also assessed. Training effects on outcome variables were estimated by two-way factorial ANCOVA using the study group and menopausal status as fixed factors. Bone structural strength was better maintained among the trainees. At the femoral neck, there was a small but significant 2% training effect in the bone mass distribution (p=0.05). At the tibial diaphysis, slight 1% to 2% training effects (p=0.03) in total cross-sectional area and bone structural strength were observed (p=0.03) among the postmenopausal trainees. Also, 3% to 4% training effects were observed in the figure-8 running time (p=0.03) and grip strength (p=0.01). In conclusion, vigorous aerobic impact exercise training has potential to maintain bone structural strength and improve physical performance among breast cancer survivors.

Effect of supervised and home exercise training on bone mineral density among breast cancer patients. A 12-month randomised controlled trial.

UNLABELLED: The ability of combined step aerobic- and circuit-training to prevent bone loss after breast cancer treatments was related to skeletal site and patients' menopausal status. Among premenopausal breast cancer survivors, a 12-month exercise intervention completely prevented bone loss at the femoral neck, whereas no exercise effect was seen at lumbar spine or at neither site in postmenopausal women. INTRODUCTION: The primary objective of this randomised clinical trial was to determine the preventive effect of supervised weight-bearing jumping exercises and circuit training on bone loss among breast cancer patients. METHODS: Of 573 breast cancer survivors aged 35-68 years randomly allocated into exercise or control group after adjuvant treatments, 498 (87%) were included in the final analysis. The 12-month exercise intervention comprised weekly supervised step aerobic- and circuit-exercises and similar home training. Bone mineral density (BMD) at lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry. Physical performance was assessed by 2-km walking and figure-8 running tests, and the amount of physical activity was estimated in metabolic equivalent-hours/week. RESULTS: In premenopausal women, bone loss at the femoral neck was prevented by exercise, the mean BMD changes being -0.2% among the trainees vs. -1.4% among the controls (p = 0.01). Lumbar bone loss could not be prevented (-1.9% vs. -2.2%). In postmenopausal women, no significant exercise-effect on BMD was found either at the lumbar spine (-1.6% vs. -2.1%) or femoral neck (-1.1% vs. -1.1%). CONCLUSIONS: This 12-month aerobic jumping and circuit training intervention completely prevented femoral neck bone loss in premenopausal breast cancer patients, whereas no effect on BMD was seen in postmenopausal women.

Breast cancer in very young women.

AIMS: The purpose was to analyse the characteristics, treatment, recurrences and survival of very young women with breast cancer. METHODS: 212 female breast cancer patients ≤35 years old were treated during 1997-2007. The median follow-up time was 78 months. RESULTS: 117 patients had lymph node metastases and 14 distant metastases at diagnosis. 81 (38%) tumours were hormone receptor negative and 130 (65%) grade 3. HER2 positivity was seen in 47 (34%) and triple negativity in 35 (26%) of the 137 tumours with known HER2 status. 140 women were treated with mastectomy and 68 with breast conserving surgery. 163 patients received postoperative radiotherapy, 175 adjuvant chemotherapy, 95 endocrine therapy and 18 trastuzumab. 63 patients experienced a recurrence, of which 20 had only a locoregional recurrence. 10 (15%) of the women with breast conserving surgery experienced ipsilateral breast tumour recurrence while ipsilateral thoracic wall recurrence was seen in 8 patients (6%) after mastectomy. Seven of these eight patients did not receive postmastectomy radiotherapy. DFI was shorter in patients with hormone receptor positive tumours. At the end of follow-up 44 women had died. The 5-year OS was 80%. CONCLUSIONS: The 5-year OS for young women has become better but is still lower than for all breast cancer patients. DFI was shorter in patients with hormone receptor positive disease. Locoregional recurrences were seen more often after breast conserving surgery.

Quality of life and physical performance and activity of breast cancer patients after adjuvant treatments.

OBJECTIVE: The study aimed at investigating the quality of life (QoL) and physical performance and activity, and their interrelations, in Finnish female breast cancer patients shortly after adjuvant treatments. METHODS: A total of 537 disease-free breast cancer survivors aged 35-68 years were surveyed at the beginning of a one year randomized exercise intervention. The patients were interviewed using EORTC QLQ-C30, FACIT-F, RBDI, and WHQ (for vasomotor symptoms) questionnaires. Physical performance was tested by a 2 km walking test. Physical activity was measured by a questionnaire and a prospective two-week diary. Multivariate analysis was used to study the factors associated with QoL. RESULTS: About 26% of the patients were rated as depressed, 20.4% as fatigued, and 82% suffered from menopausal symptoms. The global QoL was lower than in general population (69.4 vs 74.7, p<0.001). About 62% of the walking test results were below the population average. Fatigue (p<0.001), depression (p<0.001), body mass index (p = 0.016) and comorbidity (p = 0.032) impaired, and physical activity (p = 0.003) improved QoL. Physical activity level correlated positively to physical performance (r = -0.274, p<0.0001). CONCLUSIONS: The QoL of the patients shortly after adjuvant treatments was impaired and the physical performance poor as compared to general population. In particular, depression and fatigue were related to impaired QoL. Physical performance and activity level were the only factors that correlated positively to QoL. Thus, physical exercise could be useful in rehabilitation of cancer survivors, especially for depressed and fatigued patients.

Antidepressants for neuropathic pain.

BACKGROUND: This is an updated version of the original Cochrane review published in Issue 3, 2005 of The Cochrane Library. For many years antidepressant drugs have been used to manage neuropathic pain, and are often the first choice treatment. It is not clear, however, which antidepressant is more effective, what role the newer antidepressants can play in treating neuropathic pain, and what adverse effects are experienced by patients. OBJECTIVES: To determine the analgesic effectiveness and safety of antidepressant drugs in neuropathic pain. SEARCH STRATEGY: Randomised controlled trials (RCTs) of antidepressants in neuropathic pain were identified in MEDLINE (1966 to Oct 2005); EMBASE (1980 to Oct 2005); the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, Issue 3, 2005; and the Cochrane Pain, Palliative and Supportive Care Trials Register (May 2002). Additional reports were identified from the reference list of the retrieved papers, and by contacting investigators. SELECTION CRITERIA: RCTs reporting the analgesic effects of antidepressant drugs in adult patients, with subjective assessment of pain of neuropathic origin. Studies that included patients with chronic headache and migraine were excluded. DATA COLLECTION AND ANALYSIS: Two review authors agreed the included studies, extracted data, and assessed methodological quality independently. Sixty one trials of 20 antidepressants were considered eligible (3293 participants) for inclusion. Relative Risk (RR) and Number-Needed-to-Treat (NNTs) were calculated from dichotomous data for effectiveness and adverse effects. This update includes 11 additional studies (778 participants). MAIN RESULTS: Sixty one RCTs were included in total. Tricyclic antidepressants (TCAs) are effective and have an NNT of 3.6 (95% CI 3 to 4.5) RR 2.1 (95% CI 1.8 to 2.5) for the achievement of at least moderate pain relief. There is limited evidence for the effectiveness of the newer SSRIs but no studies of SNRIs were found. Venlafaxine (three studies) has an NNT of 3.1 (95% CI 2.2 to 5.1) RR 2.2 (95% CI 1.5 to 3.1). There were insufficient data to assess effectiveness for other antidepressants such as St Johns Wort and L-tryptophan. For diabetic neuropathy the NNT for effectiveness was 1.3 (95% CI 1.2 to 1.5) RR 12.4 (95% CI 5.2 to 29.2) (five studies); for postherpetic neuralgia 2.7 (95% CI 2 to 4.1), RR 2.2 (95% CI 1.6 to 3.1) (four studies). There was evidence that TCAs are not effective in HIV-related neuropathies. The number needed to harm (NNH) for major adverse effects defined as an event leading to withdrawal from a study was 28 (95% CI 17.6 to 68.9) for amitriptyline and 16.2 (95% CI 8 to 436) for venlafaxine. The NNH for minor adverse effects was 6 (95% CI 4.2 to 10.7) for amitriptyline and 9.6 (95% CI 3.5 to 13) for venlafaxine. AUTHORS' CONCLUSIONS: This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Three-year oral clodronate treatment does not impair mineralization of newly formed bone--a histomorphometric study.

Bisphosphonates have been used successfully in the treatment of malignant hypercalcemia and skeletal metastases. Recently, clodronate has been studied in adjuvant settings in primary breast cancer. However, long-term effect of adjuvant clodronate on bone histology has not been reported, whereas bone mineral density studies have been published. The aim of this study was to examine the effect and safety of long-term clodronate treatment on bone quality as measured by histomorphometric techniques from bone biopsies. A total of 299 patients with early stage breast cancer were randomized to receive adjuvant oral clodronate (1.6 g/day) or to a control group for 3 years. All patients had adjuvant treatment: premenopausal women had six cycles of chemotherapy and postmenopausal women had antiestrogen for 3 years. Trabecular bone quality was examined in transiliac bone biopsy specimens by using histomorphometric techniques in 28 clodronate treated and 35 control patients who were disease-free at 3 years and who allowed the biopsy specimen to be obtained. No statistically significant differences were found in the values of osteoid, mineral apposition rate, or mineralization lag time in bone biopsies between the clodronate and the control groups. Postmenopausal women who received two antiresorptive drugs, antiestrogen and clodronate, developed features of secondary hyperparathyroidism with increased eroded surface and osteoclast number. In premenopausal, women clodronate with adjuvant chemotherapy, which induced early menopause and rapid bone loss in most of the patients, seemed to conduct slight depression in bone formation. Three-year oral clodronate treatment does not impair mineralization of newly formed bone: however, clodronate with different adjuvant breast cancer treatments has a diverse impact on bone histomorphometry depending on the type of therapy.

Antidepressants for neuropathic pain.

BACKGROUND: For many years antidepressant drugs have been used to manage neuropathic pain, and are often the first choice treatment. It is not clear, however, which antidepressant is more effective, what role the newer antidepressants can play in treating neuropathic pain, and what adverse effects are experienced by patients. OBJECTIVES: To determine the analgesic effectiveness and safety of antidepressant drugs in neuropathic pain. Migraine and headache studies were not considered. SEARCH STRATEGY: Randomised trials of antidepressants in neuropathic pain were identified in MEDLINE (1966 to Dec 2003); EMBASE (1980 to Dec 2003); the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2004, Issue 1; and the Cochrane Pain, Palliative and Supportive Care Trials Register (May 2002). Additional reports were identified from the reference list of the retrieved papers, and by contacting investigators. SELECTION CRITERIA: Randomised trials reporting the analgesic effects of antidepressant drugs in adult patients, with subjective assessment of pain of neuropathic origin. Studies that included patients with chronic headache and migraine were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers agreed the included studies, extracted data, and assessed methodological quality independently. Fifty trials of 19 antidepressants were considered eligible (2515 patients) for inclusion. Relative Risk (RR) estimates and Number-Needed-to-Treat (NNTs) were calculated from dichotomous data for effectiveness and adverse effects. MAIN RESULTS: Tricyclic antidepressants (TCAs) are effective treatments for the treatment of neuropathic pain. Amitriptyline has an NNT of 2 (95%CI 1.7 to 2.5) RR 4.1(95%CI 2.9-5.9) for the achievement of at least moderate pain relief. There is limited evidence for the effectiveness of the newer selective serotonin reuptake inhibitor antidepressant drugs (SSRIs). There were insufficient data for an assessment of evidence of effectiveness for other antidepressants such as St Johns Wort, venlafaxine and L-tryptophan. For diabetic neuropathy the NNT for effectiveness was 1.3 (95%CI 1.2 to 1.5) RR 12.4(95%CI 5.2-29.2) (five studies); for postherpetic neuralgia 2.2 (95%CI 1.7 to 3.1), RR 4.8(95%CI 2.5-9.5)(three studies). There was evidence that TCAs are not effective in HIV-related neuropathies. The number needed to harm(NNH) for major adverse effects defined as an event leading to withdrawal from a study was 16 (95%CI: 10-45). The NNH for minor adverse effects was 4.6 (95%CI 3.3-6.7) AUTHORS' CONCLUSIONS: Antidepressants are effective for a variety of neuropathic pains. The best evidence available is for amitriptyline. There are only limited data for the effectiveness of SSRIs. It is not possible to identify the most effective antidepressant until more studies of SSRIs are conducted.

Clodronate treatment influences MMP-2 associated outcome in node positive breast cancer.

PURPOSE: Serum postoperative matrix metalloproteinase 2 (MMP-2) level is a predictor of outcome in node positive breast cancer and can be used to stratify patients into low and high risk groups. Our aim was to determine how clodronate treatment influences MMP-2 associated clinical outcome. PATIENTS AND METHODS: Women with primary node-positive breast cancer were randomized to control group or to receive oral clodronate for 3 years. Adjuvant chemo- or endocrine therapy was given to all patients. The follow-up time for all patients was 5 years. MMP-2 and MMP-9 levels were quantitatively measured from the serum of 252 patients before and after 1 year clodronate treatment using enzyme-linked immunoassays. RESULTS: In clodronate-treated patients, postoperative MMP-2 levels did not predict 5-year disease-free survival or overall survival (DFS, in low MMP-2 group (<5.32 ng/ml, median) 53% versus in high MMP-2 group (>median) 63%, p=NS; OS, 68% versus 63%, p=NS). When the patients were grouped according to serum MMP-2 levels, survival rates among patients with low MMP-levels were better in control than clodronate treated patients (DFS, 82% versus 53%, p = 0.003; OS, 91% versus 68%, p=0.014). Among patients with high serum MMP-2 levels, no significant difference in DFS or OS was found between control and clodronate groups. In multivariate analysis of low risk patients, independent predictors for DFS were treatment, age, nodal and PgR status, and those for OS treatment together with nodal and ER status. During 12 months follow-up, MMP-2 levels increased significantly more in clodonate receiving patients than in controls (p = 0.002). In comparison, when the patients were grouped according to MMP-9 levels, clodronate also impaired DFS among patients with low MMP-9 levels (82% versus 53%, p = 0.02), but no influence on OS was observed (83% versus 70%, p = 0.09). CONCLUSIONS: Clodronate interferes with the prognostic value of serum MMP-2. Clodronate has a negative impact on outcome among patients with low serum MMP-2 and MMP-9 levels, while no such influence is observed among patients with high MMP-2 and MMP-9 levels.

Tamoxifen treatment reverses the adverse effects of chemotherapy-induced ovarian failure on serum lipids.

In all, 146 premenopausal women with early stage breast cancer were treated with adjuvant chemotherapy. In addition, 5-year tamoxifen treatment was started after chemotherapy to those 112 patients with hormone-receptor-positive tumours while those with hormone-receptor-negative tumours received no further therapy. The serum lipid levels were followed in both groups. The levels of serum total and low-density lipoprotein (LDL) cholesterol increased significantly after chemotherapy only in patients who developed ovarian dysfunction. Total cholesterol increased +9.5% and LDL cholesterol +16.6% in patients who developed amenorrhoea (P<0.00001 and 0.00001, respectively). The cholesterol levels did not change in patients who preserved regular menstruation after chemotherapy. After 6 months of tamoxifen therapy, the total cholesterol decreased -9.7% and the LDL cholesterol -16.7% from levels after the chemotherapy, while the cholesterol concentrations remained at increased levels in the control group (P=0.001 and P<0.0001, respectively). The high-density lipoprotein cholesterol levels did not change significantly in either tamoxifen or control group. The effects of tamoxifen treatment on serum lipids after chemotherapy have not been studied before. Our current study suggests that adjuvant tamoxifen therapy reverses the adverse effects of chemotherapy-induced ovarian failure on total and LDL cholesterol and even lowers their serum levels below the baseline.

Phase I trial on sms-D70 somatostatin analogue in advanced prostate and renal cell cancer.

Plasma concentrations and tolerability of a novel somatostatin analogue sms-D70 were studied in patients with metastatic hormone-resistant prostate cancer (HRPC) or metastatic renal cell cancer. To overcome the limitations of the octapeptides having affinity only to somatostatin receptor subtypes 2 and 5, HRPC expressing mainly somatostatin receptors 1 and 4, a somatostatin derivative based on the natural somatostatin having affinity to all five somatostatin receptor subtypes, was developed. The in vivo stability of this dextran-conjugated derivative, somatostatin-D70, was confirmed previously in animal studies, and the nanomolar "panaffinity" has been shown in in vitro receptor binding studies on cell lines transfected with the somatostatin receptor genes. Sms-D70 was given with subcutaneous injection once a week at dose levels of 5, 10, 20, 35, and 50 mg. For pharmacokinetic studies, sms-D70 was labeled with 131I. Fourteen patients were treated, of whom 10 had prostate and 4 renal cell cancer. The kinetic data revealed high stability with a long half-life in the blood. The drug was well tolerated, and no grade 4 (WHO) toxicity was observed. The maximal tolerated dose could not be established due to the lack of dose-limiting toxicities. Objective PSA responses were not recorded in these heavily treated patients, but subjective stabilization of pain was observed and urinary symptoms were alleviated in four patients. Three patients with metastatic HRPC received 5-10-mg intravenous injections of sms-D70 once weekly for 4-14 months on a compassionate use basis. In all cases, serum PSA values decreased more than 50% from the pretreatment level, but these results are difficult to interpret due to concomitant treatments given to these patients. In conclusion, sms-D70 was well tolerated in the treatment of metastatic prostate and renal cell cancer, but no responses were found in these heavily treated patients.