The Canadian journal of oncology最新文献

High-dose chemotherapy (HDC) with stem cell autografting produces complete remission (CR) rates far in excess of those reported for lower-dose chemotherapy, or for any form of endocrine manipulation in patients with metastatic breast cancer. In early studies involving patients with resistant disease, HDC produced CR rates of as high as 25%. Most contemporary HDC trials accrue patients who are responding to "conventional" chemotherapy, and hence, few untreated patients have been studied in phase II evaluations. In one case, a CR rate of 54% (25% of which remained durable) was reported. In a randomized trial of high-dose versus conventionally dosed therapy, investigators in South Africa reported complete response rates of 50% and 6% respectively. In trials in which HDC is applied as a form of consolidation therapy following "conventional" chemotherapy, complete remission rates as high as 70% are reported.

Trial designs traditionally used in the development of new anti-cancer agents are usually categorized as phase I, phase II, phase III and phase IV. Such trials are often performed in patients with metastatic cancer. Phase I trials are conducted in small numbers of patients to determine a drug's maximally tolerated dose (MTD) and toxicity profile. In phase II studies, the anti-tumor activity of the new agent is tested in different tumor types. If a drug is found to be promising in phase II studies, it is then compared to standard therapy through a randomized trial design in phase III studies. In phase IV studies, the efficacy and safety profile of the drug are evaluated in a standard clinical setting. In the field of oncology, studies have been conducted in which agents already approved by the regulatory agency are combined with other anti-cancer drugs and evaluated for anti-tumor efficacy. These have also been termed phase II studies.

"Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility." This particular definition of osteoporosis was proposed at the Fourth International Symposium on Osteoporosis (Consensus Conference) in Hong Kong in April 1993; it attempts to combine the description of low bone mass with the risk for consequent fractures.

In incurable breast cancer all therapy is palliative, i.e. intended primarily to relieve symptoms, preserve health-related quality of life (HQL) and, if possible, prolong life without undue toxicity and loss of HQL. In this situation the measure of success if the extent to which palliative therapy achieves these goals. Unless the effects of therapy on symptoms and HQL are measured, it will never be certain whether the goals of palliation are being achieved. Recent studies in metastatic breast cancer have begun to focus on these goals, and the results are encouraging. It is becoming clear that HQL is improved by using appropriately aggressive chemotherapy, with the benefits outweighing the deleterious effects of treatment toxicity. In addition, there are some unexpected results indicating that pre-treatment HQL may be a better predictor of response, on-treatment HQL and length of survival than other known prognostic variables. These advances in our understanding of HQL in metastatic breast cancer will aid in the development of rational treatment policies for the management of this disease.

The number of deaths due to breast cancer in Ontario in 1990 has been over 1700. Although hormone treatment and polychemotherapy in advanced breast cancer have been introduced many years ago for patients with metastatic breast cancer, the median survival time for this patient subpopulation, who either have hormone receptor negative tumors or have failed hormone therapy, remains between 15-18 months. Fewer than 20% of all patients are alive three years after the diagnosis of metastatic disease. Some other studies have demonstrated that dose-escalation with growth factor and/or stem cell support (from the bone marrow or peripheral blood) has shown a higher response rate including complete remissions.

High-dose chemotherapy (HDCT) and autotransplantation of hematopoietic cell is being investigated as a therapy for either metastatic or localized high-risk breast cancer. Breast cancer has a tendency to metastasize to the bones and the bone marrow (BM) and therefore the probability of harvesting malignant cells when collecting stem cells for autotransplantation appears high. Thus, the elimination or decrease of this contamination in the transplanted product appears mandatory. Autologous peripheral blood stem cell transplantation (PBSCT) has shown significant advantages over autologous bone marrow transplantation (ABMT) in improving the feasibility of HDCT, while possibly limiting the BM contamination. The transplantation of only CD34+ products may even be a further advance. The role of ex vivo purging of cancer cells has not been established in ABMT or PBSCT. The question remains if the positive selection of CD34+ products is sufficient for controlling cancer cell contamination or if this product should be purged as well. The review of the literature suggests that contamination of the bone marrow could have an impact in terms or risk of relapse and could thus play a role as a pejorative prognostic factor. These data, although not totally adequate for the autotransplantation setting, are raising concerns over the probability of reinfusing malignant cells at time of autotransplantation following HDCT. There is a tremendous need to address these concerns in the laboratory along with prospective clinical trials. Until further data is available, this risk must be taken into consideration when patients with breast cancer are treated with curative intent.

Because lung cancer is a major health care problem in Canada, it would be useful to identify the direct health care costs of diagnosing and treating this disease and to create an analytic framework within which diagnostic and therapeutic options can be assessed. This paper describes a method of modelling the costs of care for lung cancer. The perspective of the costing model is that of the government as payer in a universal health care system. Clinical algorithms were developed to describe the management of non-small cell (NSCLC) and small cell (SCLC) lung cancer. Patients were allocated to the treatment algorithms in the model, based on a knowledge of the stage distribution of cases within provincial cancer registries and an estimate of the use of therapeutic modalities, according to lung cancer experts. A microsimulation model (POHEM) developed at Statistics Canada was used to integrate data on risk factors, disease onset and progression, health care resource utilization and direct medical care costs. The model incorporates survival data on patients, according to cell type and stage, based on published studies. Relapse and terminal care costs were assigned during the year of death, in order to determine the cost of continuing care and the cumulative cost of lung cancer management over time. Patients surviving five years were assumed to be cured. The model estimates that the total five year cost to provide care to the 15,624 cases of lung cancer diagnosed in Canada in 1988 was in excess of $328 million. Over 82% of this total was spent in the first year for diagnostic tests, therapy (surgery, chemotherapy, radiation therapy, or combinations of these), hospitalization and follow-up costs. The average five year cost per case was $21,000, and ranged from a high of $29,860 for limited disease SCLC, to a low of $16,500 for Stage IV NSCLC. The actual cost of providing care, including the management of complications, is unknown and our estimates should be regarded as an idealized estimate of the cost of lung cancer management. However, the POHEM model has a level of sophistication which, we believe, reasonably reflects the cost per case and total costs of treating lung cancer by stage and therapeutic modality in Canada.

The anti-tumor effect and toxicity of chemotherapeutic agents are dose-related. The dose-response curve for these agents is sigmoidal with a threshold, a lag phase, a linear phase and a plateau phase. The aim of cancer chemotherapy is to exploit the difference between the response curves for the tumor and normal tissues. In the laboratory and in some animal models, the dose-response curve for many agents demonstrates a log-linear relationship between dose and cell kill so that a doubling of the drug dose may increase cell kill by ten-fold. The more effective a drug is, the steeper the dose-response curve. Dose may be an important variable in the outcome of therapy, however, this dose-response relationship has been difficult to demonstrate because a dose-response effect may not be evident for most human tumors in the dose ranges used in clinical trials.

The phase I trial in breast cancer conducted by Peters et al. defined a regimen of high-dose chemotherapy consisting of cyclophosphamide, cisplatinum and BCNU (CPA/cDDP/BCNU). In chemotherapy-resistant metastatic disease, 23% of patients achieved complete remission followed by early relapse. In a phase II study, 53% of stage IV patients with no prior treatment achieved complete response (CR) with 16% progression-free at five to nine years post-transplant. Chemically debulking with an Adriamycin, 5FU, and Methotrexate regimen (AFM) to minimal tumor burden achieved 68% CR, with approximately 20% disease-free patients at 36 months. Other high dose chemotherapy regimens have been developed, again demonstrating in stage IV patients complete remissions in excess of 65% and progression-free survival rates of 20-30%.

Bone metastases present major clinical challenges to oncologists. They are common, require a variety of palliative treatments and are associated with a decline in quality of life. Diagnosis and assessment currently rely principally on the structural consequences of metastatic bone involvement. In this review, imaging techniques, biochemical markers bone metabolism. Subjective and quality of life assessments and marrow markers are discussed and their place in diagnosis and monitoring of response to treatment considered.