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BACKGROUND: Studies have shown that utilities for a particular treatment, elicited by means of a hypothetical treatment scenario, may remain stable within the same patients when examined before, during, and after experiencing that treatment (within-group stability). However, other studies have found that utilities for a particular health state may differ between patient groups who are and who are not experiencing the particular health state (between-group differences). OBJECTIVE: The authors evaluated this apparent contradiction in the case of adjuvant chemotherapy for breast cancer. A related purpose was to examine whether a chemotherapy scenario adequately reflects the patients' own experiences with chemotherapy. METHOD: Forty-three patients with early-stage breast cancer evaluated their actually experienced health state and a chemotherapy scenario before, during, and after undergoing adjuvant chemotherapy (chemotherapy group). A control group of 51 patients for whom chemotherapy was not part of the treatment plan was interviewed at similar points in time. Utilities were elicited by means of a visual analog scale (VAS), a chained time trade-off (TTO), and a chained standard gamble (SG). RESULTS: The utilities for the chemotherapy scenario remained relatively stable over time in the 2 patient groups. Furthermore, the chemotherapy scenario was evaluated more positively by patients in the chemotherapy group than by control patients (e.g., utilities before chemotherapy: VAS 0.69 vs. 0.50, TTO 0.88 vs. 0.50, SG 0.92 vs. 0.58, all Ps < 0.01). Finally, patients in the chemotherapy group evaluated their actually experienced health states during chemotherapy higher than the chemotherapy scenario that was assessed at the same time (VAS 0.79 vs. 0.69, TTO 0.93 vs. 0.87, SG 0.97 vs. 0.96, all Ps < 0.05). CONCLUSIONS: Both within-group stability and between-group differences were found. A possible explanation for within-group stability may be that the chemotherapy scenario did not fully correspond to the patients' actual experiences with chemotherapy ('noncorresponding description'). Therefore, preferences did not change even when the patients' own clinical health status had changed. The between-group differences may be explained by 'anticipated adaptation.' Both explanations may work together to explain why utilities remain stable within the same patients but differ between different patient groups. [ABSTRACT FROM AUTHOR]

Background: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival.Methods: Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63) were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) for biomarker finding. Initial results were validated by analysis of sample set II (n = 371), using one-dimensional gel-electrophoresis.Results: In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity 20), identified as haptoglobin (Hp) alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014). Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2), of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 - 1.34, p = 0.5221) and 1.03 (95% CI: 0.65 - 1.64, p = 0.8966) for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II.Conclusion: In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive). This study illustrates the importance of validation in obtaining the true clinical applicability of a potential biomarker. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy improves outcome in osteosarcoma. Determination of optimum regimens for survival, toxicity and prognostic factors requires randomised controlled trials to be conducted., Patients and Methods: Between 1983 and 2002, the European Osteosarcoma Intergroup recruited 1067 patients with localised extremity osteosarcoma to three randomised controlled trials. Standard treatment in each was doxorubicin 75 mg/m(2) and cisplatin 100 mg/m(2). Comparators were addition of methotrexate (BO02/80831), a multidrug regimen (BO03/80861) and a dose-intense schedule (BO06/80931). Standard survival analysis methods were used to identify prognostic factors, temporal and other influences on outcome., Results: Five- and 10-year survival were 56% (95% confidence interval 53% to 59%) and 52%, respectively (49% to 55%), with no difference between trials or treatment arms. Median follow-up was 9.4 years. Age range was 3-40 years (median 15). Limb salvage was achieved in 69%. Five hundred and thirty-three patients received the standard arm, 79% completing treatment. Good histological response to preoperative chemotherapy, distal tumour location (all sites other than proximal humerus/femur) and female gender were associated with improved survival., Conclusions: Localised osteosarcoma will be cured in 50% of patients with cisplatin and doxorubicin. Large randomised trials can be conducted in this rare cancer. Failure to improve survival over 20 years argues for concerted collaborative international efforts to identify and rapidly test new treatments.

Aim: Chemotherapy-induced toxicity is an independent prognostic indicator in several cancers. We aimed to determine whether toxicity was related to survival and histological response in high-grade localised extremity osteosarcoma. We undertook a retrospective analysis of patients treated within three consecutive randomised controlled trials (RCTs) of the European Osteosarcoma Intergroup., Methods: Between 1982 and 2002, 533 patients were randomised to six cycles of doxorubicin 75 mg/m(2) and cisplatin 100 mg/m(2). Toxicity data were collected prospectively and graded according to the World Health Organisation (WHO) criteria. Standard univariate and multivariate models were constructed to examine the relationship between reported toxicity, survival, and histological response., Results: Five- and 10-year overall survival was 57% (95% confidence interval (CI) 52-61%) and 53% (49-58%), respectively. Grades 3-4 oral mucositis (hazard ratio (HR) 0.51, 95% CI 0.29-0.91), grades 1-2 nausea/vomiting (HR 0.37, 95% CI 0.16-0.85), grades 1-2 thrombocytopenia (HR 0.49, 95% CI 0.27-0.87), good histological response (HR 0.42, 95% CI 0.27-0.65), and distal tumour site (HR 0.45, 95% CI 0.28-0.71) were associated with improved survival in multivariate analysis. The only factors that were independently associated with histological response were older age (odds ratio (OR) 0.18, 95% CI 0.04-0.72) and chondroblastic tumour (OR 0.28, 95% CI 0.10-0.77), both being associated with a significantly lower chance of achieving a good response., Conclusion: Chemotherapy-induced toxicity predicts survival in patients with localised extremity osteosarcoma. Investigation of the pharmacogenomic mechanisms of constitutional chemosensitivity underlying these observations will present opportunities for personalising treatment and could lead to improved outcomes., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Background: Recurrence after osteosarcoma usually leads to death; thus prognostic factors for survival are of great importance., Methods: Between 1983 and 2002, the European Osteosarcoma Intergroup accrued 1067 patients to 3 randomized controlled trials of pre- and post-operative chemotherapy for patients with resectable non-metastatic high-grade osteosarcoma of the extremity. Control treatment in all trials was doxorubicin 75 mg/m² and cisplatin 100mg/m². The comparators were additional high-dose methotrexate (BO02), T10-based multi-drug regimen (BO03) and G-CSF intensified-DC (BO06). Post-recurrence survival (PRS) was investigated on combined data with standard survival analysis methods., Results: Median recurrence-free survival was 31 months; 8 recurrences were reported more than 5 years after the diagnosis. In 564 patients with a recurrence (median 13 months post-randomisation), there was no difference in post-relapse survival between treatment arms. Patients whose disease recurred within 2 years after randomization had a worse prognosis than those recurring after 2 years. Patients with good initial histological response to pre-operative chemotherapy had a better overall survival after recurrence than poor responders. Local relapse was more often reported after limb-saving procedures (2 versus 8%; amputation versus limb-saving), independent of the primary tumour site. Site of first recurrence (local 20%, lung 62%, "other" 19%) affected survival, as patients recurring with non-lung distant metastases only or any combination of local relapse, lung metastases and non-lung metastases (=group "other") had significantly worse overall survival (local 39%, lung 19%, "other" 9% at 5 years)., Conclusions: These data describing a large series of patients with recurrent extremity osteosarcoma confirm the relationship between early recurrence and poor survival. There was better PRS in patients after good histological response to pre-operative chemotherapy, or with local-only recurrence., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Aim: The majority of clinicians, radiologists and pathologists have limited experience with soft tissue sarcomas. In 2004, national guidelines were established in The Netherlands to improve the quality of diagnosis and treatment of these rare tumours. This study evaluates the compliance with the guidelines over time., Patients: Population-based series of 119 operated patients with a soft tissue sarcoma (STS) diagnosed in 1998-1999 (79 before implementation of new guidelines) and in 2006 (40 after implementation)., Methods: Coded information regarding patient and tumour characteristics as well as (the results of) pathology review was collected from the medical patient file by two experienced data-managers., Results: Diagnostic imaging of the tumour was performed according to the guidelines in 75-100% depending on the site of the tumour (abdominal versus non-abdominal) as well as the time of diagnosis. Adherence to the guidelines with respect to invasive diagnostic procedures in patients with non-abdominal STS improved over time. A pre-operative histological diagnosis was obtained in 42% of the patients in 1998-1999 and in 72% of the patients in 2006 (p<0.001). The guidelines for reporting on pathology were increasingly adhered to. In 2006, (nearly) all pathology reports mentioned tumour size, morphology, tumour grade, resection margins and radicality. This represents a major improvement compared to the pathology reports in 1998-1999, where these aspects were not mentioned in 14-40% of the cases. The proportion of prospective pathology reviews by (a member of) the expert panel increased from 60% in 1998-1999 to 90% in 2006 (p=0.001)., Discussion: The compliance with the guidelines has been optimised by the increased attention to this group of patients. Most important factors have been the reporting of the results of the first evaluation and (discussions about) the centralisation of treatment. Further improvements could be reached by the prospective web based registry monitoring logistic aspects as well as parameters useful for the evaluation of the quality of care.

Neutropenia following high-dose chemotherapy leads to a high incidence of infectious complications, of which central venous catheter-related infections predominate. Catheter-related infections and associated risk factors in 392 patients participating in a randomized adjuvant breast cancer trial and assigned to receive high-dose chemotherapy and peripheral stem-cell reinfusion were evaluated. Median catheter dwell time was 25 days (range 1-141). Catheter-related infections were seen in 28.3% of patients (11 infections per 1000 catheter-days). Coagulase-negative staphylococci were found in 104 of 186 positive blood cultures (56%). No systemic fungal infections occurred. Cox regression analysis showed that duration of neutropenia >10 days (P=0.04), using the catheter for both stem-cell apheresis and high-dose chemotherapy (P= <0.01), and use of total parenteral nutrition (TPN, P=0.04) were predictive for catheter-related infections. In conclusion, a high incidence of catheter-related infections after high-dose chemotherapy was seen related to duration of neutropenia, use of the catheter for both stem-cell apheresis and high-dose chemotherapy, and use of TPN. Selective use and choice of catheters could lead to a substantial reduction of catheter-related infectious complications.

Background: Previous randomized controlled trials that used the two-drug chemotherapy regimen of cisplatin and doxorubicin as the conventional arm showed no evidence of benefit from an increase in the number of agents or the length of treatment. It was then proposed that survival could be improved by increasing the planned dose intensity of cisplatin and doxorubicin., Methods: Previously untreated patients with nonmetastatic, high-grade, central osteosarcoma of an extremity were randomly assigned to Regimen-C (conventional treatment with six 3-week cycles of cisplatin [100 mg/m2 by 24-hour infusion] and doxorubicin [25 mg/m2/day by 4-hour infusion for 3 days]) or to Regimen-DI (intensified treatment with identical total doses of cisplatin and doxorubicin, planned as six 2-week cycles supported by granulocyte colony stimulating factor (G-CSF). Surgery was scheduled for week 6 in both arms. Primary and secondary outcome measures were overall and progression-free survival, respectively. Intention-to-treat analyses were performed using standard survival analysis methods. Landmark analyses were performed in patients with known surgical details and centrally reviewed histologic response. All statistical tests were two-sided., Results: Between May 1993 and September 2002, treatment was randomly allocated to 497 eligible patients. Six cycles of chemotherapy were completed by 78% of patients in Regimen-C and 80% of patients in Regimen-DI. The delivered preoperative median dose intensity of cisplatin was 86% in Regimen-C and 111% in Regimen-DI (as the percentage of that planned for the conventional regimen). Postoperative median dose intensity of cisplatin was 82% in Regimen-C and 110% in Regimen-DI (the corresponding figures for doxorubicin dose intensity were similar). Regimen-DI was associated with lower risks of severe leucopenia and neutropenia and higher risks of thrombocytopenia and mucositis. Good histologic response (>90% tumor necrosis) was observed in 36% of Regimen-C patients and 50% of Regimen-DI patients (P = .003, chi2 test). There was no evidence of a difference in overall survival (hazard ratio [HR] = 0.94, 95% CI = 0.71 to 1.24; P = .64) or progression-free survival (HR = 0.98, 95% CI = 0.77 to 1.24; P = .83). Landmark analyses showed similar results., Conclusions: Planned intensification of chemotherapy with cisplatin and doxorubicin increased received dose intensity and resulted in a statistically significant increase in favorable histologic response rate, but not in increased progression-free or overall survival. Our results call into question the use of histologic response as a surrogate outcome measure in trials of this disease.

Benefit from chemotherapy treatment in breast cancer patients is determined by the molecular make-up of the tumour. In a retrospective analysis, we determined the molecular subtypes of breast cancer originally defined by expression microarrays by immunohistochemistry in tumours of patients who took part in a randomised study of adjuvant high-dose chemotherapy in breast cancer. In addition, the topoisomerase II alpha (TOP2A) amplification status was determined by fluorescence in situ hybridisation and chromogenic in situ hybridisation. 411 of the 753 tumours (55%) were classified as luminal-like, 137 (18%) as basal-like and 205 (27%) as human epithelial receptor type 2 (HER2) amplified. The basal-like tumours were defined as having no expression of ER and HER2; 98 of them did express epidermal growth factor receptor and/or cytokeratin 5/6. The luminal-like tumours had a significantly better recurrence free and overall survival than the other two groups. From the 194 HER2-positive tumours, 47 (24%) were shown to harbour an amplification of TOP2A. Patients with an HER2-amplified tumour randomised to the high-dose therapy arm did worse than those in the conventional treatment arm, possibly caused by the lower cumulative anthracycline dose in the high-dose arm. The tumours with a TOP2A amplification contributed hardly to this difference, suggesting that TOP2A amplification is not the cause of the steep dose-response curve for anthracyclines in breast cancer. Possibly, the difference of the cumulative dose of only 25% between the treatment arms was insufficient to yield a survival difference.

A patient previously treated for bilateral breast cancer with mastectomy, radiation therapy and in remission on hormonal therapy for more than five years presented with abdominal symptoms from breast cancer relapse. She developed inappropriate polyuria and hypernatraemia, which responded to desmopressin. In combination with the absence of a high signal from the posterior lobe of the pituitary on MRI , these data indicated the presence of partial central diabetes insipidus. The anterior pituitary showed partial failure (low follicle-stimulating hormone, luteinising hormone and insulin-like growth factor-1 levels). Furthermore, primary adrenal insufficiency had developed, ascribed to bilateral tumour invasion of the adrenals. This rare combination of endocrinological failures in a patient with metastatic breast cancer is discussed.

Background: High-dose chemotherapy in the adjuvant treatment of breast cancer has been abandoned by many., Patients and Methods: 885 patients with stage III primary breast cancer and four or more axillary lymph node metastases were randomised to receive either five courses of FEC (fluorouracil, epirubicin and cyclophosphamide) followed by radiation therapy and tamoxifen, or the same treatment but with high-dose alkylating chemotherapy (cyclophosphamide, thiotepa and carboplatin) replacing the fifth course of FEC. Of these patients, 621 had HER2/neu-negative disease, as determined by immunohistochemistry and chromogenic in situ hybridisation., Results: At a median follow-up of 84 months, a trend for a better relapse-free survival was observed in the high-dose arm: (hazard ratio (HR) 0.84, P = 0.076, two-sided). The 621 patients with HER2/neu-negative disease benefited from high-dose therapy, while patients with HER2/neu-positive disease did not (test for interaction, P = 0.006). There was a marked relapse-free survival benefit for patients with HER2/neu-negative disease (71.5% versus 59.1%, 5 years after randomisation; HR 0.68, P = 0.002) and also a survival benefit (78.2% versus 71.0% at 5 years; HR 0.72, P = 0.02)., Conclusions: The findings from this subgroup analysis provide additional evidence that HER2/neu-positive breast cancer is relatively resistant to alkylating agents. For HER2/neu-negative tumours, however, high-dose chemotherapy should remain the subject of clinical studies.

Purpose: Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients., Patients and Methods: Eight hundred eighty-five patients were randomly assigned between two chemotherapy regimens both followed by radiotherapy and tamoxifen. Fatigue was assessed using vitality scale (score < or = 46 defined as fatigue), poor mental health using mental health scale (score < or = 56 defined as poor mental health) both of Short-Form 36, muscle and joint pain with Rotterdam Symptom Checklist, and Hb levels were assessed before and 1, 2, and 3 years after chemotherapy., Results: Fatigue was reported in 20% of 430 assessable patients (202 standard-dose, 228 high-dose) with at least a 3-year follow-up, without change over time or difference between treatment arms. Mean Hb levels were lower following high-dose chemotherapy. Only 5% of patients experienced fatigue and anemia. Mental health score was the strongest fatigue predictor at all assessment moments. Menopausal status had no effect on fatigue. Linear mixed effect models showed that the higher the Hb level (P = .0006) and mental health score (P < .0001), the less fatigue was experienced. Joint (P < .0001) and muscle pain (P = .0283) were associated with more fatigue., Conclusion: In 3 years after treatment, no significant differences in fatigue were found between standard and high-dose chemotherapy. Fatigue did not change over time. The strongest fatigue predictor was poor mental health.

Purpose: Hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome) is characterized by the development of cancer of the colorectum, endometrium and other cancers. Cancer of the ovaries (OC) has frequently been reported in HNPCC. Colorectal cancer associated with HNPCC has a better survival chance compared to sporadic colorectal cancer. It is yet unknown whether patients with OC from HNPCC families (OC-HNPCC) also have a better survival. Therefore, the aim of the study was to compare the survival between patients with OC-HNPCC and a control group., Methods: A total of 26 patients with OC were identified from the Dutch HNPCC Registry. A control group (52 cases) matched for age, stage and year of diagnosis was derived from the population-based Eindhoven Cancer Registry. Data on treatment were collected for all patients. Kaplan-Meier analysis was used to calculate the crude survival., Results: The mean age at diagnosis of OC-HNPCC was significantly lower than the age of sporadic OC (49.5 vs 60.9 years). Compared to sporadic OC, OC-HNPCC was diagnosed at an earlier stage. The survival rate was not significantly different between patients with OC-HNPCC and the controls with sporadic OC. The cumulative 5-year-survival rates were 64.2 and 58.1% respectively., Conclusion: On the basis of our findings, we recommend to treat OC-HNPCC similar to sporadic OC.

There are limited data that define the role of chemotherapy in the treatment of high-grade spindle cell sarcomas of bone, other than osteosarcoma or malignant fibrous histiocytoma (MFH-B). This prospective study evaluates the effect of doxorubicin and cisplatin on these tumours. Thirty-seven patients, age 65 years, with spindle cell sarcoma of bone, except osteosarcoma or MFH-B, were included. Chemotherapy consisted of doxorubicin and cisplatin every 3 weeks for six cycles. Resection was performed after three cycles. In 15 patients with metastases, response assessment showed three complete responses (CR), four stable disease (SD), five progression; three were not evaluable. Median time to progression was 30 months (95% Confidence Interval (CI), 8-51 months) for the operable non-metastatic patients; median survival 41 months (95% CI, 16-82 months). Median time to progression in the metastatic group was 10 months (95% CI, 0-18 months) and median survival was 14 months (95% CI, 4-45 months). This study suggests a limited role for doxorubicin and cisplatin in metastatic high-grade spindle cell sarcoma of bone, other than osteosarcoma or MFH-B cases.

Purpose: There is limited knowledge of risk factors for breast cancer recurrence within 2 years. This study aimed to predict early failure and identify high-risk patients for prognostic and therapeutic purposes., Experimental Design: We studied 739 patients from a randomized trial who were <56 years of age and had >/=4 or more positive lymph nodes, no distant metastases, and no previous other malignancies. After complete surgical treatment, patients received conventional-dose anthracycline-based chemotherapy or a high-dose scheme of anthracycline-based plus alkylating chemotherapy. We assessed clinical and (immuno)histological parameters to predict recurrence within 2 years., Results: Early failure occurred in 19% (n = 137). Median survival after early failure was limited to 0.7 year. Estrogen and progesterone receptor negativity and visceral relapse predicted poor prognosis. Early failure was associated with young age, large tumors, high histological grade, angio-invasion, apical node metastasis, and >/=10 involved nodes. Estrogen receptor, progesterone receptor, and p27 negativity; HER2 overexpression; and p53 positivity also predicted early failure. The surgical or chemotherapy regimen and histological type did not. The same parameters except tumor size were associated with early death. Grade III, >/=10 involved nodes, and estrogen receptor negativity were independently associated with early failure and together identified a subset of patients (7%) with 3-fold increased early failure and 5-fold increased early death., Conclusions: Early failure is associated with poor survival. The combination of three commonly determined parameters constitutes a strong predictive model for early failure and death.

The optimal duration of cytostatic treatment for metastatic breast cancer is still a matter of debate. Possible gain in the duration of remission has to be weighed against the side-effects of treatment. Our aim was to define the optimal duration of cyclophosphamide, methotrexate, 5-fluorouracil (CMF) treatment by studying the time to treatment failure, overall survival and using a Q-TWiST analysis. The treating physician's opinion was asked. The European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer Group conducted a randomised trial in 204 non-progressing metastatic breast cancer patients after induction chemotherapy (CMF) to stop or continue treatment. Progression-free (PFS) and overall survival (OS) were studied. To gain more insight into the burden of treatment-related side-effects, Q-TWiST was analysed. In addition, we asked for oncologists' preferences as patients are likely to be influenced by their physicians' opinion. Continuation of CMF had a significantly longer time to treatment failure (TTF) 5.2 versus 3.5 months (P=0.011). There was no overall survival (OS) difference 14.0 versus 14.4 months (P=0.77). Mean quality-adjusted survival time was equal to 8.4 months for no further treatment and decreased to 7.9 months for continuation of CMF (95% Confidence Interval (CI) of difference equals 0.5+/-2.5 months). Almost half of the oncologists said they would favour continuous treatment for a 3-month gain in time to progression-a difference which was not found in this study. Based on these data, an interruption of chemotherapy (CMF), if this is the wish of the patient, is justified.

When making decisions about adjuvant chemotherapy for early-stage breast cancer, costs and benefits of treatment should be carefully weighed. In this process, patients' preferences are of major importance. The objectives of the present study were: (1) to determine the minimum benefits that patients need to find chemotherapy acceptable, and (2) to explore potential preference determinants, namely: positive experience of the treatment, reconciliation with the treatment decision, and demographic variables. Preferences were elicited from patients scheduled for adjuvant chemotherapy (chemotherapy group: n = 38) before (T(1)), during (T(2)), and 1 month after chemotherapy (T(3)), and were compared to responses from patients not scheduled for chemotherapy (no-chemotherapy group: n = 38). The patients were asked, for a hypothetical situation, to indicate the minimum benefit (in terms of improved 5-year disease-free survival) to find adjuvant chemotherapy acceptable. In the chemotherapy group, the median benefit was 1% at all 3 measurement points. In the no-chemotherapy group the attitude towards chemotherapy became more negative over time, although not statistically significantly so (T(1): 12%, T(2): 15%, T(3): 15%; P = 0.10). At all measurement points, the patients in the chemotherapy group indicated that they would accept chemotherapy for significantly (P< 0.01) less benefit than the patients in the no-chemotherapy group. Of the demographic variables, age was related to preferences, but only at T(2)and only in the no-chemotherapy group. The more positive attitude towards chemotherapy and the stability of preferences in the chemotherapy group indicated that reconciliation with the treatment decision was a more important determinant of patients' preferences than positive experience of the treatment., (Copyright 2001 Cancer Research Campaign.)

Objective: To investigate tumor response rate and treatment toxicity of a modified combination chemotherapy consisting of bleomycin (B), methotrexate (M), and CCNU (C) for patients with locally advanced, squamous-cell carcinoma of the vulva (not amenable to resection by standard radical vulvectomy) or recurrent disease (after incomplete resection). Tumor resectability was reassessed in patients who had responded to chemotherapy., Methods: The regimen consisted of bleomycin 5 mg intramuscular (im) days 1-5, CCNU 40 mg per os (po) days 5-7, and methotrexate 15 mg po days 1 and 4 during the first week. During weeks 2-6 the patient was administered bleomycin 5 mg im days 1 and 4, and methotrexate 15 mg po on day 1 of the week. This 6-week cycle was repeated at 49-day intervals., Results: Twenty-five eligible patients with a median age of 66 years (range, 39-82 years) were entered in this phase II trial. Twelve patients had primary locally advanced disease, 13 patients had a locoregional recurrence, and all received up to three BMC cycles. Two complete and twelve partial responses were observed (response rate, 56%; 95% confidence limits, 35-76%). The BMC regimen was associated with major hematological side effects and mild signs of bleomycin-related pulmonary toxicity. At a median follow-up of 8 months, 3 patients were alive, 18 had died due to malignant disease, 2 had died due to toxicity, and 2 had died due to intercurrent disease and unknown cause. The median progression-free survival was 4.8 months and the median survival was 7.8 months. The 1-year survival was 32% (95% confidence limits, 13-51%)., Conclusion: The present data confirm the therapeutic activity of the BMC regimen in locoregionally advanced or recurrent squamous-cell carcinoma of the vulva. Following neoadjuvant chemotherapy, the overall response rate was 56%. BMC is an outpatient treatment that may play a role in the palliative therapy of advanced or recurrent vulva cancer., (Copyright 2001 Academic Press.)

Objective: To investigate the clinical activity and toxicity of a combination chemotherapy consisting of cyclophosphamide (C), adriamycin (A) and cisplatin (P) for patients with primary adenocarcinoma of the Fallopian tube having FIGO stage III-IV disease., Methods: The CAP-regimen consisted of cyclophosphamide 600 mg/m2, adriamycin 45 mg/m2, and cisplatin 50 mg/m2 administered intravenously on day one every 28 days., Results: Twenty-four eligible patients with histologically-confirmed Fallopian tube adenocarcinoma were entered in the trial. Fourteen patients had FIGO stage III, and ten had stage IV disease. The median number of CAP cycles was six. Ten patients had a complete and six had a partial response (response rate: 67%, 95% confidence limits: 45-84%). WHO grade III-IV side-effects included haematological toxicity, nausea/vomiting and alopecia. Furthermore, mild signs of cisplatin-related peripheral neurotoxicity were observed. At a median follow-up of 40 months, nine patients were alive and 15 had died due to malignant disease. The median time to progression was 13 months for all patients. The median overall survival was 24 months and the 1-, 3- and 5-year survival and their 95% confidence limits were 73% (54-92%), 25% (4-46%) and 19% (0-38%), respectively., Conclusion: The present data confirm the therapeutic activity of the CAP-regimen in primary Fallopian tube adenocarcinoma. The response rate is moderate and the toxicity profile is acceptable.

There is an abundance of evidence that adjuvant systemic therapy with chemotherapy or endocrine therapy results in better survival for all patients with resectable breast cancer. The absolute 10-year survival advantage however varies for the different patient groups. Therefore, for each individual patient the choice of adjuvant therapy must take into account the potential benefits and the possible side effects. A group of medical oncologists from the Dutch National Breast Cancer Platform (NABON) and the Dutch Society for Medical Oncology (NVMO) prepared a guideline for the treatment of patients with early resectable breast cancer. The criterium for choosing adjuvant systemic therapy for the individual patient is an expected increase in 10-year survival of 5% or more. In the guideline a difference is made between patients with and without axillary lymph node metastasis. In patients with axillary lymph node metastasis the choice for adjuvant systemic therapy depends on the following prognostic factors: menopausal status, age, and the presence of estrogen and progesterone receptors in the tumour. In patients without axillary lymph node metastasis the choice depends also on the following prognostic factors: the size of the tumour, the mitotic activity index, or the histopathologic grade of differentiation.

In medicine, response shift refers to a change--as a result of an event such as a therapy--in the meaning of one's self-evaluation of quality of life. Due to response shift, estimates of side effects of radiotherapy may be attenuated if patients adapt to treatment toxicities. The purpose of our study was to assess to what extent two components of response shift, scale recalibration and changes in values, occur in early-stage breast cancer patients undergoing radiotherapy and to examine what the implications would be for treatment evaluation. In the week before start of post-operative radiotherapy, 46 patients filled out a questionnaire consisting of quality of life items of the SF-36 and the Rotterdam symptom checklist (RSCL) (pretest). During radiotherapy, patients were asked to fill out the questionnaire twice: a posttest (quality of life at that moment) and a thentest (quality of life before treatment, retrospectively), supposedly using the same internal standard. Changes in values were studied by asking the patients on the two occasions to rate the importance of seven attributes representing various domains of quality of life. Patients were also asked whether their quality of life with respect to the measured aspects had changed since the pretest (subjective transition scores). Significant scale recalibration effects were observed in the areas of fatigue and overall quality of life. When the groups were divided according to their subjective transition scores, significant scale recalibration effects were found in case of worsened quality of life for fatigue and overall quality of life, and in case of improved quality of life for fatigue and psychological well-being. The mean importance ratings remained fairly stable over time, except for 'skin reactions', which obtained less importance at the end of radiotherapy than before. In conclusion, effects of scale recalibration were observed that would have significantly affected quality of life evaluations, in that the impact of radiotherapy on fatigue and overall quality of life would have been underestimated. Changes in internal values were observed only for 'skin reactions'.

Objective: Many studies suggest that impaired health states are valued more positively when experienced than when hypothetical. This study investigated to what extent this discrepancy occurs and examined four possible explanations: non-corresponding description of the hypothetical health state, new understanding due to experience with the health state, valuation shift due to a new status quo, and instability of preference., Patients and Methods: Fifty-five breast cancer patients evaluated their actually experienced health state, a radiotherapy scenario, and a chemotherapy control scenario before, during, and after postoperative radiotherapy. Utilities were elicited by means of a visual analog scale (VAS), a chained time tradeoff (TTO), and a chained standard gamble (SG)., Results: The discrepancy was found for all methods and was statistically significant for the TTO (predicted utilities: 0.89, actual utilities: 0.92, p < or = 0.05). During radiotherapy, significant differences (p < or = 0.01) were found between the utilities for the radiotherapy scenario and the actual health state by means of the VAS and the SG, suggesting non-corresponding description as an explanation. The utilities of the radiotherapy scenario and the chemotherapy control scenario remained stable over time, and thus new understanding, valuation shift, and instability could be ruled out as explanations., Conclusion: Utilities obtained through hypothetical scenarios may not be valid predictors of the value judgments of actually experienced health states. The discrepancy in this study seems to have been due to differences between the situations in question (non-corresponding descriptions).

In the assessment of health-related quality of life, nonpreference-based methods usually show only moderate correlations with utility-based measures. One cause may be that patients assign different weights to the various domains of health-related quality of life, for which nonpreference-based methods usually do not allow. Utilities reflect a weighted sum of these domains. The aim of this study is to assess whether the relationship between utility-based methods and nonpreference-based measures improves through the use of individual importance weights for the various domains of health-related quality of life. For this purpose, weights were obtained from 41 early-stage breast cancer patients, both before and during treatment, for seven pre-selected health status attributes representing important domains of health-related quality of life during chemotherapy. The importance weights were combined with the level of functioning on the attributes. These scores were regressed against patients' utilities for their actually experienced health state during chemotherapy, measured by means of a visual analog scale (VAS), a time trade-off (TTO), and a standard gamble (SG). Before weighting, the seven attribute scores were more strongly related to TTO and SG utilities than the nonpreference-based questionnaires. However, when they were combined with the importance weights, only the correlation with the SG utilities improved, and only so with the importance weights obtained before chemotherapy. In this study, assigning individually assessed preference weights to self-reported level of functioning did not result in stronger relationships with utilities.

The "classical" CMF (cyclophosphamide/methotrexate/5-fluorouracil) schedule was compared with a modified 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer, as concern had arisen as to whether the classical schedule was the optimal way to give these drugs. The response rate with classical CMF was 48% compared with 29% for intravenous CMF (P = 0.003). Response duration was similar at 11 months, but survival longer for the classical schedule (17 versus 12 months, P = 0.016). We conclude that classical CMF is the superior regimen and attribute this to the higher dose intensity achieved.