Rearrangements in the 11q23 region, the site of the mixed lineage leukaemia (MLL) gene, are found in both childhood acute myeloid (AML) and lymphoblastic (ALL) leukaemia. We studied the in vitro drug resistance by the fluorometric microculture cytotoxicity assay (FMCA) in 132 children with AML and 178 children with ALL (aged 0-17 years). In AML, children with t(9;11) (n = 10) were significantly more sensitive to cytarabine (P
A report by The Swedish Council on Technology Assessment in Health Care (SBU) has reviewed, classified, and graded the scientific literature on cancer chemotherapy in some major tumor types, described the practice of chemotherapy in Sweden, compared practice with scientific knowledge, and analyzed the costs and cost-effectiveness of chemotherapy. This article summarizes the overall conclusions. The literature on the effects of chemotherapy is extensive. Chemotherapy has a well-documented role in the curative and palliative treatment of patients with several types of cancer. In Sweden, chemotherapy is used largely in keeping with applications documented in the scientific literature.
A systematic review of the effect of chemotherapy in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The review also included an assessment of the limited number of studies available on the health economics of chemotherapy for diagnoses included in the SBU report. The conclusions reached from this assessment can be summarized as follows: Several international studies and one Swedish study addressed the cost-effectiveness of different chemotherapeutic regimens. The quality of the studies is generally low and comparability is rather limited. Some of the studies compared cytostatic treatment with no cytostatic treatment. Most studies, however, compared two or more treatments. The costs were then compared with potential differences in treatment outcome. Outcomes are mostly measured as the cost per life-year gained. The results from these studies vary by treatment and indication. In some cases, after all relevant costs are taken into account, chemotherapy shows cost savings. In most studies, chemotherapy is associated both with higher costs and improved treatment results, often measured in terms of survival. Studies of rather high quality show that the cost per life-year gained (quality-adjusted) for most chemotherapeutic regimens with relatively limited effects ranges between 100,000 and 250,000 Swedish kronor (SEK). Estimates of cost-effectiveness for more effective chemotherapy has not been reported in the literature. The estimated costs are in parity with the costs of 'established' treatments for other diseases. There is uncertainty about what treatments can be considered cost-effective; there is no consensus concerning what costs are 'reasonable' per life-year gained in health care. The estimates of cost-effectiveness in most studies are highly uncertain and must be interpreted with caution. Improved assessment would require more studies in Sweden. For various reasons it is difficult to apply the results from the international studies to Sweden.
It is necessary to carry out randomised clinical cancer trials (RCTs) in order to evaluate new, potentially useful treatments for future cancer patients. Participation in clinical trials plays an important role in determining whether a new treatment is the best therapy or not. Therefore, it is important to understand on what basis patients decide to participate in clinical trials and to investigate the implications of this understanding for optimising the information process related to study participation. The aims of this study were to (1) describe motives associated with participation in RCTs, (2) assess if patients comprehend the information related to trial enrolment, and (3) describe patient experiences of trial participation. Questionnaires were sent to 96 cancer patients participating in one of nine ongoing clinical phase 3 trials at the Department of Oncology, Uppsala University Hospital in Sweden. Eighty-eight patients completed the questionnaire (response rate 92%); 95% of these were patients in adjuvant therapy and 5% participated in clinical trials on palliative care. Two main reasons for participation were identified: personal hope for a cure and altruism. Patients show adequate understanding of the information provided to them in the consent process and participation entails high patient satisfaction.
BACKGROUND: To determine whether the change in tumor diameters at the first follow-up computed tomography (CT) examination after baseline examination (first change) correlates with outcome in patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy. PATIENTS AND METHODS: The first change was analyzed in a multicenter randomized phase III trial (Nordic VI, N = 567) comparing first-line irinotecan with either bolus or infused 5-fluorouracil. Cox proportional hazards multiple regression model and Kaplan-Meier survival analyses after correction for guarantee-time bias were carried out to evaluate correlations between first change, objective response according to RECIST 1.0, progression-free survival (PFS), and overall survival (OS). RESULTS: The hazard ratios for PFS and OS decreased along with first change. A decrease between 10% and 20%. CONCLUSIONS: The change in tumor size at the first follow-up CT is strongly prognostic for PFS and OS in mCRC.
Since May 1996 all Nordic countries have been participating in a study of childhood acute myeloid leukemia (AML). The aim is to correlate the in vitro sensitivity of leukemic cells and individual plasma concentrations of cytotoxic drugs with clinical effect. Blast cells from bone marrow and/or peripheral blood are tested against a panel of cytotoxic agents using the fluorometric microculture cytotoxicity assay (FMCA). Plasma concentrations of cytotoxic drugs are analysed during induction therapy. Bone marrow samples from the participating centres generally reached the analysing laboratory within 24 hours. 61 out of 71 (86%) samples were successfully analysed, 47 de novo AML and 14 relapses. Relapsing patients tended to have a more resistant test profile than newly diagnosed patients. Steady state plasma levels of doxorubicin, etoposide and 6-thioguanine nucleotide varied about 10-fold between patients. The intra-individual variation was much less, suggesting that dose adjustment based on pharmacokinetic data might be useful in the future.
Our aim is to study whether or not in vitro sensitivity of leukemic cells correlates with clinical effect; if so, in vitro testing might used for stratification of treatment. During 1995-1997 bone marrow samples from 145 Swedish children with newly diagnosed acute lymphoblastic leukemia were analysed by the automated fluorometric microculture cytotoxicity assay. Therapeutic effect was evaluated by bone marrow morphology day 15 and 29. Preliminary results indicate that marrow samples from patients with poor response to induction therapy show a higher degree of in vitro resistance to several cytotoxic drugs at diagnosis than good responders.
The aim of this study was to compare debulking surgery and cytoreductive surgery (CRS) in patients with Pseudomyxoma peritonei (PMP) regarding efficacy and safety.
Data were extracted from medical records and treatment outcomes were analyzed for all 152 patients with PMP who were scheduled for debulking surgery and intraperitoneal chemotherapy (IPC) or CRS and IPC at Uppsala University Hospital, Uppsala, Sweden, between September 1993 and December 2008.
One hundred and ten patients (73%) were treated with CRS and IPC and 40 (27%) with debulking surgery and IPC. In two patients (1%), surgery was defined as open and close. Patients with CRS and IPC had a 74% 5-year overall survival (OS) rate compared with 40% for those treated with debulking surgery (P
A prospective study on total utilisation of cytotoxic drugs for selected cancers was carried out in two Swedish health service regions, during four weeks in the autumn of 1997. The study included 1,590 patients; 1,169 with solid tumours and 421 with haematological malignancies. The majority of patients (75% to 80%) were treated at university/regional hospitals, often at oncology or haematology departments, and most received treatment as outpatients. Furthermore, most were treated according to recommendations in regional or national clinical guidelines, so-called care programmes, although the percentage varied by diagnosis. Only 10% were participants in a clinical trial. In approximately 40% of the patients, treatment was aimed at cure. However, this percentage varied between 0% and 94% depending on tumour type. At the population level, a comparison of the scientific evidence according to a literature review (Acta Oncol, this issue) with the survey showed that treatment with cytotoxic drugs in Sweden was largely evidence-based. A high percentage of patients received cytotoxic drugs for diseases where recommendations to treat were strong, i.e. outcomes were well-documented in the literature. A low percentage of patients received chemotherapy in disease settings with little or no scientific documentation. The percentage of patients treated was also limited in cases where the effects of chemotherapy are relatively small, although scientifically well-documented. For methodological reasons, one cannot exclude the possibility that cytotoxic drugs may be overutilised at the individual level for palliative purposes, e.g. by not discontinuing treatment despite the absence of clinical benefits. Likewise, one cannot exclude the possibility of underutilisation, e.g. by patients declining treatment because they were not informed about the potential benefits.