[Is comorbidity a prognostic factor in premenopausal women with breast cancer?].
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Biomedical subjects
Publications and source records attributed to E Wist.
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BACKGROUND: Chemotherapy drug distribution varies greatly among individual patients. Therefore, we developed an individualised fluorouracil, epirubicin, cyclophosphamide (FEC) regimen to improve outcomes in patients with high-risk early breast cancer. We then did a randomised trial to compare this individually tailored FEC regimen with conventional adjuvant chemotherapy followed by consolidation with high-dose chemotherapy with stem-cell support. METHODS: 525 women younger than 60 years of age with high-risk primary breast cancer were randomised after surgery to receive nine cycles of tailored FEC to haematological equitoxicity with granulocyte colony-stimulating factor (G-CSF) support (n=251), or three cycles of FEC at standard doses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb), and peripheral-blood stem-cell or bone-marrow support (n=274). Both groups received locoregional radiation therapy and tamoxifen for 5 years. The primary outcome measure was relapse-free survival, and analysis was by intention to treat. FINDINGS: At a median follow-up of 34.3 months, there were 81 breast-cancer relapses in the tailored FEC group versus 113 in the CTCb group (double triangular method p=0.04). 60 deaths occurred in the tailored FEC group and 82 in the CTCb group (log-rank p=0.12). Patients in the CTCb group experienced more grade 3 or 4 acute toxicity compared with the tailored FEC group (p<0.0001). Two treatment-related deaths (0.7%) occurred in the CTCb group. Six patients in the tailored FEC group developed acute myeloid leukaemia and three developed myelodysplastic syndrome. INTERPRETATION: Tailored FEC with G-CSF support resulted in a significantly improved relapse-free survival and fewer grade 3 and 4 toxicities compared with marrow-supported high-dose chemotherapy with CTCb as adjuvant therapy of women with high-risk primary breast cancer.
p53 is a transcription factor that participates in cell cycle checkpoint processes and apoptosis. The protein product of the murine double minute gene 2 (mdm-2) plays a central role in the regulation of p53. In response to DNA-damaging agents, the wild-type p53-activated fragment 1 (WAF1 also known as p21) is an important downstream effector in the p53-specific growth arrest pathway. In breast cancer patients, it is unclear whether measuring p53, mdm-2, or p21 expression provides information on how patients will respond to chemotherapy. Mib-1 monoclonal antibody recognizes the proliferation-related antigen Ki-67. High tumor proliferation has previously been associated with response to chemotherapy. p53, mdm-2, p21, and mib-1 expression were assessed by immunohistochemical methods in primary tumors derived from 134 patients who took part in a randomized multicenter trial comparing docetaxel to sequential methotrexate and 5-fluorouracil (MF) in advanced breast cancer. Low mib-1 staining correlated with negative p53 staining (P = 0.001), and mdm-2 and p21 stainings correlated positively with each other (P < 0.001). p53, mdm-2, p21, and mib-1 expression were not significantly associated with response to chemotherapy, time to progression, or overall survival in the whole patient population or in the docetaxel group. However, in the MF group, a low mib expression (<25%) and a high mdm-2 expression (> or =10%) predicted a better response (P = 0.014 and P = 0.046, respectively) to treatment and a longer time to progression in both univariate and multivariate analyses. p53 staining status was not associated with response to treatment in either group. Interestingly, tumors with both negative mdm-2 and p21 expression, irrespective of p53 status, had a high response rate to docetaxel but no response to MF. Although highly preliminary, the findings suggest that different tumor biological factors may predict response to different chemotherapy regimens with distinct mechanisms of action. The results of our phenotype analysis also indicate that it is more likely that a panel of tumor biological factors instead of only one single factor may be needed for better prediction of chemotherapy response.
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The aim of this study was to compare the efficacy and tolerability of docetaxel to methotrexate and 5-fluorouracil in advanced breast cancer after anthracycline failure. A randomised multicentre trial was conducted in 283 patients with advanced breast cancer who had failed previous anthracycline treatment. Docetaxel at a dose of 100 mg/m2 every 3 weeks (n = 143) was compared with sequential methotrexate and 5-fluorouracil (MF; n = 139) given at day 1 and 8 every 3 weeks at dosages of 200 mg/ m2 and 600 mg/m2, respectively. After progression, crossover to the alternative treatment group was recommended. There was a significantly higher overall response rate in the docetaxel 42% (CR 8% + PR 34%) than in the MF arm 21% (CR 3% + PR 18%) (P < 0.001). The median time to progression (TTP) was 6.3 months in the docetaxel arm and 3.0 months in the MF arm (P < 0.001). Docetaxel also had a significantly higher response rate of 27% following crossover compared with MF (12%). Significantly more side-effects (leucopenia, infections, neuropathy, oedema, asthenia, skin, nail changes, alopecia) were seen in the docetaxel than in the MF group. However, grade 3 and 4 side-effects were infrequent with both drugs, with the exception of fatigue, alopecia and infections. Median overall survival (OS) including crossover phase was 10.4 months in the docetaxel and 11.1 months in the MF arm (P = 0.79). Based on the response rate and the primary endpoint of TTP, docetaxel is superior to sequential methotrexate and 5-fluorouracil in advanced breast cancer after anthracycline failure.
There are contrasting reports upon the level of effectiveness of motor imagery in learning new motor skills, but there is general consensus that motor imagery can lead to improvements in performance, especially in combination with physical practice. In the present study we examined the effectiveness of motor imagery in the acquisition of movement invariants in two grapho-motor trajectorial learning tasks with differing visuospatial components: 'Ideogram drawing' and 'connecting circles'. Two subject groups were studied: An imagery group, which underwent 10 min of motor imagery training and a control group, which practised a control visuomotor task over the same period of time. The results showed that imagery training alone enabled the subjects to achieve a significant approach to movement isochrony as well as a significant shifting of peak velocity toward the target. After a practice phase, both groups improved their performance, but the imagery group was still significantly faster than the control group. Furthermore, a series of tests measuring visual imagery abilities was administered to the subjects. There were however no significant relationships between the motor performance and the visual imagery ability levels of the subjects. It is concluded that motor imagery can improve the acquisition of the spatio-temporal patterns of grapho-motor trajectories and that there are different processes involved in visual and motor imagery.
In a multicentre phase III study of disseminated malignant melanoma performed in Sweden and Norway, 326 patients were randomised to receive treatment with the combination dacarbazine [DTIC] (D) and vindesine (V) with or without the addition of cisplatin (P). D was given intravenously (i.v.) at a dose of 250 mg/m2 days 1-5 every 4 weeks and V was given i.v. at a dose of 3.0 mg/m2 day 1 weekly. P was given i.v. at a dose of 100 mg/m2 day 1 every 4 weeks. There was no statistically significant difference in overall survival between the treatment arms (P = 0.22). Increased toxicity was observed in the treatment arm containing P of which leucopenia, alopecia and nausea/vomiting were the most pronounced. The median time to progression was significantly longer in patients treated with DVP (4.2 versus 2.2 months, P = 0.007). In conclusion, adding P to DV did not change overall survival but did significantly increase toxicity.
The effect of droloxifene (3-hydroxytamoxifen) given as first-line endocrine treatment was evaluated in 39 postmenopausal women with advanced receptor-positive or receptor-unknown breast cancer. The patients had not received any previous anticancer therapy apart from adjuvant treatment. The overall response rate (CR + PR) was 51% (8% CR, 43% PR), 95% confidence interval+/-15.7%. Median time to progression (all patients) was 8 months, the median time to response 2 months, while the median duration of response was 10 months. The drug was well tolerated with no major side effects recorded; 16% of the patients experienced hot flushes. The response to droloxifene recorded in the present study is in accordance with the response rates to tamoxifen as first-line treatment in identical groups of patients.
PURPOSE: To investigate the prospective pattern of use of alternative medicine, here called nonproven therapy (NPT), among oncologic patients during a 5-year period, and the relationship between this use and survival, a questionnaire-based follow-up study was performed at the Department of Oncology, University of Tromsø, from 1990 to 1996. PATIENTS AND METHODS: Two-hundred fifty-two patients answered the first questionnaire during the period July 1990 to July 1991. Eligible patients were mailed follow-up questionnaires after 4, 12, 24 and 60 months. A telephone interview performed after the last follow-up questionnaire showed little disagreement with the prospective collected information as regards the number of patients reported as users of NPT (kappa, 0.92). RESULTS: The number of patients who reported ever using NPT in each cross-sectional part of the study varied between 17.4% and 27.3%. However, the estimated cumulative risk of being a user of NPT during the follow-up period was 45%. Seventy-four percent of NPT users in this north Norwegian study population used faith healing or healing by hand (spiritual NPT) alone or in combination with other forms of NPT. The proportion of patients who used spiritual versus nonspiritual forms of NPT was consistent throughout the follow-up period. Women were more often users than men (50% v 31%, P = .002). Patients older than 75 years of age seldomly used NPT. The 5-year observed survival rate was not influenced by the use of NPT. Adjusted for sex, age, and diagnosis, patients with a high educational level had a borderline higher 5-year survival rate than patients with less education (P = .06). CONCLUSION: Our results demonstrate that cross-sectionally designed studies will underestimate the number of ever-users of NPT in a cancer patient population. The use of NPT does not influence observed survival among cancer patients seen in north Norway.
In the period 1986 to 94, 173 women who had had a lumpectomy or a mastectomy were treated with radiotherapy at the University Hospital of Tromsø. The median diagnostic delay was 2.4 months (range 0-98.6 months). Three out of four patients were operated on within two weeks of the diagnosis being made. About two thirds experienced a delay of more than six weeks from the operation to the start of radiotherapy treatment. The five-year overall survival rate in the mastectomy and postoperative radiotherapy group was 67%. Patients with estrogen receptor positive tumours had a better prognosis. Only 5% and 7% of all patients in our region in stages I and II had breast conserving surgery (BCS) during the study period (66 patients). The five-year overall survival rate in the BCS group was 77%. BCS raised the cost per patient by about 3,000 GBP compared to modified radical mastectomy (MRM). The cost per QALY using BCS as against MRM was about 12,000 GBP. We conclude that MRM should not be used instead of BCS merely for economical reasons.
A national multi-centre study was performed to investigate the prevalent use of alternative medicine, or non-proven therapies, among Norwegian cancer patients. Of 911 patients invited to take part in the study 642 were included in the final analysis. Among the 630 assessable patients, 20% had been or were current users of non-proven therapies. In the northern most and western parts of Norway the most preferred alternative methods are healing by hand and faith healing, while herbs, vitamins, diets and Iscador are popular in the central and southern parts. Use of nonproven therapies is common in the northern part of the country. Prevalent users are middle-aged patients with long-standing symptomatic disease and former users of non-proven therapies for nonmalignant disease. About 40% of the patients would like non-proven therapies to be an option in hospital. Most of the users of non-proven therapies (80%) had consulted practitioners of scientific medicine first; 15% had started treatment with non-proven therapies simultaneously. The users of non-proven therapies report having received less hope of cure (30%) from their physicians than the non-users (50%) had. Most of the users had learned about non-proven therapies from friends or relatives. Most users believe that non-proven therapies might make them stronger and relieve their symptoms. Very few patients believe in a cure (10%). Nearly 40% felt that non-proven therapies had no definite effect on them. Four patients reported adverse effects. 15 patients had been treated abroad, usually in Denmark.
Between 1985-93, 55 patients were treated for Hodgkin's disease at the University Hospital of Tromsø. The median diagnostic delay was four months and a significant prolonged delay was connected with the lymphocyte predominance subgroup. The ChlVPP regimen was shown to be a risk factor for herpes zoster virus infection. The 5-year overall survival was 90%. The survivors experienced a low frequency of symptoms and a high level of functioning. The females reported a significant superior global quality of life and had a lower psychological distress and fatigue score than the males. The cost of one quality-adjusted life year (QALY) (production gains included and using a 10% discount rate) was estimated to be 1,651 pounds. This makes Hodgkin's disease one of the most cost-effective malignancies to treat.
This study addressed the use of alternative medicine, here called non-proven therapies (NPTs), among hospitalized Norwegian cancer patients. A total of 126 (20%) of the assessable 630 patients were users of NPTs. Approximately 43% of all patients and more than 60% of the users of NPTs stated that they would like NPTs to be an option in hospitals belonging to the National Health Service. Most users of NPTs (82%) consulted traditional medicine first, while 15% started treatment with NPTs simultaneously. Users of NPTs reported to have received less hope of a cure (30%) from their physicians than non-users (50%). Users mostly learned about NPTs from friends and relatives. Most users believed that NPTs might give them strength and relieve their symptoms. Very few patients believed in a cure (10%). Nearly 40% were uncertain of any effect of the NPTs or felt there had been no effect. 4 patients reported adverse effects. 15 patients had been treated abroad, most of them in Denmark. Expenses incurred through use of NPTs were mostly moderate, but some patients used large sums of money. Patients' opinions on whether or not the treatment had been expensive were closely linked to their anticipation of the effect of the treatment.
A questionnaire-based study was carried out at the Department of Oncology, University Hospital of Tromsø, during the period July 1990-October 1991. The 252 participating patients received a questionnaire at arrival at the oncology unit and the surviving patients a follow-up questionnaire at home 4 months later. The aim of the study was to assess whether patients' attitudes to information about their malignant disease and satisfaction with the given treatment correlated to their use of non-proven therapies (NPTs) and reported mental distress. Patients under 45 years of age significantly more often preferred comprehensive medical information than older patients (83% versus 52%, P = 0.001). Better educated patients were more satisfied with the information given by their general practitioner (GP) (P = 0.05) and at their local hospital (P = 0.02) than other patients. Of all responders, 81% of the patients treated in the department were completely satisfied with the opportunities to ask questions while 87% reported being given comprehensive information. Only 2% of the patients reported to have received unwanted information. Better educated patients expressed less satisfaction with the information given and the possibility of influencing their own treatment at the Department of Oncology (P = 0.02). Patients expressing mental distress wanted less information (P = 0.05) and expressed less satisfaction with the quality of the perceived information in the oncology unit (P = 0.004). They were also less satisfied with the treatment given (P = 0.05) and their own influence on the treatment decision (P = 0.02). Users of NPT did not feel the received treatment to be the best possible (P = 0.04).
250 patients with clinical stage 1 non-seminomatous germ cell tumours of the testis (NSGCT 1) were included into a prospective multicentre protocol during 1990-1994 and treated according to three risk strata: patients without tumour cell invasion of vascular structures in the testis (VASC-) and elevated serum AFP levels (AFP+) at orchiectomy were considered low risk (LR) and only observed closely. VASC- and AFP- or VASC+ and AFP+ patients were presumed intermediate risk (IR) and pathologically staged (PS) by retroperitoneal lymph node dissection (RPLND). VASC+ and AFP-patients were regarded as high risk (HR) and received adjuvant chemotherapy (PEB x 3). At a median observation time of 40 (7-68) months, all patients were alive and without evidence of active germ cell cancer. The actuarial relapse rate in the 106 LR patients was 22%, and 70% (14/20) had elevated serum tumour markers at relapse. One of 32 (3%) HR patients relapsed with a resectable retroperitoneal mature teratoma despite adjuvant chemotherapy. Only 14% of the 99 IR patients who underwent RPLND had PS2 disease, and the actuarial relapse rate in 85 PS1 patients was 18%. This multicentre study demonstrated that excellent therapeutic outcome is possible when 18 comparatively small urological and oncological centres follow a strict and formal cancer care programme. The useful prognostic effect of VASC was once again verified. Pathological staging by RPLND in NSGCT1 is, in our opinion, not necessary, with presumed low-risk patients offered surveillance and high-risk patients offered adjuvant chemotherapy.
The purpose of this study was to evaluate tumour response and toxicity to ifosfamide and continuous infusion etoposide in metastatic or locally advanced soft tissue sarcoma, with dose escalations under G-CSF (granulocyte colony-stimulating factor) support. Of 92 eligible patients (median age 51 years), 85% had tumours of high-grade malignancy and 82% had metastatic disease. Chemotherapy, the baseline dose, consisted of etoposide 600 mg/m2 as a 72 h infusion and ifosfamide 1500 mg/ m2/day for 3 days, followed by G-CSF support (VIG regimen). Stepwise 10% dose escalations were performed depending on haematological toxicity. For patients considered operable after induction chemotherapy, surgical resection of all identifiable residual tumour was attempted. Complete and partial response rates were 11% and 31%, for an overall response rate of 42% (95% CI 31-52%). Forty-eight per cent of courses were dose escalated by a median of 20%. Complete responders had significantly higher, and patients with progressive disease had significantly lower, dose levels than other patients. None of 20 patients with liver metastases responded despite high dose levels. Compared to a preceding pilot study, the addition of G-CSF led to significantly higher dose levels, improved schedule adherence and less haematological toxicity, but no apparent increase in response rate. In view of the modest dose of ifosfamide applied in this study, it is possible that the prolonged infusion of etoposide made a significant contribution to the regimen's antitumour activity, although this can only be determined definitively in a randomised study.
BACKGROUND: The purpose of the present study was to investigate whether a 1-month regimen of postoperative radiotherapy combined with 5-fluorouracil could reduce the local recurrence rate and improve survival in patients with Dukes B and C rectal cancer. METHODS: One hundred and forty-four patients were randomized to surgery alone or surgery combined with postoperative radiotherapy (46 Gy) and bolus 5-fluorouracil 30 min before six of the radiotherapy fractions. One hundred and thirty-six patients were eligible. RESULTS: The adjuvant treatment was well tolerated. After an observation time of 4-8 years, patients in the adjuvant treatment group had a cumulative local recurrence rate of 12 per cent compared with 30 per cent in the group that had surgery only (P = 0.01). The 5-year recurrence-free and overall survival rate was 64 per cent in the adjuvant group compared with 46 per cent (P = 0.01) and 50 per cent (P = 0.05) respectively in the surgery group. The adjusted relative risk of recurrence and death for the adjuvant group was 0.48 (95 per cent confidence interval 0.28-0.82) and 0.56 (0.33-0.94) respectively. CONCLUSION: The 1-month postoperative combination regimen improved treatment results in patients with Dukes B and C rectal cancer, in terms of local recurrence rate, recurrence-free survival and overall survival, without serious side-effects.