Drug development in solid tumors: personal perspective of Dr. Emil J Freireich's contributions.
The development of chemotherapy for patients with the major cancers progressed from the initial success attained in the treatment of acute leukemias and choriocarcinoma. Many of the principles of therapy were based on the concepts developed in the experimental laboratories and early clinical studies done at the NIH Clinical Center and other centers around the country. The purpose of this review is to describe some of the early advances in cancer therapy and show how many are based on the efforts of Dr. Emil J Freireich. Over his career, Dr. Freireich has published more than 500 papers and worked on more than 70 different drugs and combinations. The principles defined by Dr. Freireich, namely, the use of intermittent intensive chemotherapy to induce complete remissions (CRs), intensification of therapy in remission, and the use of unmaintained remissions to assess cure, have been important in developing curative chemotherapy programs in patients with acute leukemias. These same principles were applied to combination therapy of Hodgkin's disease as the nitrogen mustard, vincristine, procarbazine, and prednisone combination was developed. This led to the high CR and cure rate for this disease. The treatment of metastatic breast cancer does not produce a high proportion of CRs, and cures of metastatic disease are unlikely with chemotherapy alone. But adjuvant chemotherapy after surgery has resulted in a significant reduction in cancer mortality. Many challenges remain in increasing the cure rate for the major solid tumors. New avenues of controlling cell growth and metastases need to be explored. One approach that is exploitable is the use of drugs or nutrients to prevent cancer. Laboratory approaches are now becoming a clinical reality. (+info)
Chronic myelogenous leukemia--progress at the M. D. Anderson Cancer Center over the past two decades and future directions: first Emil J Freireich Award Lecture.
The purpose of this study was to review the progress in clinical and translational research in chronic myelogenous leukemia (CML) over the past 20 years at M.D. Anderson Cancer Center. The CML database updating the clinical and basic research investigations was reviewed as the source of this report. Publications resulting from these investigations were summarized. The long-term results with intensive chemotherapy, IFN-alpha therapy alone or in combination, autologous stem cell transplantation, and new agents such as homoharringtonine and decitabine showed encouraging results. Biological studies related to the BCR-ABL molecular abnormality, other molecular events, and the detection of minimal residual disease were detailed. Future strategies with potential promise in CML were outlined. Significant progress in understanding CML biology and in treating patients afflicted with the disease has occurred. Several therapeutic and research tools are currently investigated, which should hopefully improve further the prognosis of patients with CML. (+info)
American Society of Clinical Oncology 1998 update of recommended breast cancer surveillance guidelines.
OBJECTIVE: To determine an effective, evidence-based, postoperative surveillance strategy for the detection and treatment of recurrent breast cancer. Tests are recommended only if they have an impact on the outcomes specified by American Society of Clinical Oncology (ASCO) for clinical practice guidelines. POTENTIAL INTERVENTION: All tests described in the literature for postoperative monitoring were considered. In addition, the data were critically evaluated to determine the optimal frequency of monitoring. OUTCOME: Outcomes of interest include overall and disease-free survival, quality of life, toxicity reduction, and secondarily cost-effectiveness. EVIDENCE: A search was performed to determine all relevant articles published over the past 20 years on the efficacy of surveillance testing for breast cancer recurrence. These publications comprised both retrospective and prospective studies. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design. BENEFITS, HARMS, AND COSTS: The possible consequences of false-positive and -negative tests were considered in evaluating a preference for one of two tests providing similar information. Cost alone was not a determining factor. RECOMMENDATIONS: The attached guidelines and text summarize the updated recommendations of the ASCO breast cancer expert panel. Data are sufficient to recommend monthly breast self-examination, annual mammography of the preserved and contralateral breast, and a careful history and physical examination every 3 to 6 months for 3 years, then every 6 to 12 months for 2 years, then annually. Data are not sufficient to recommend routine bone scans, chest radiographs, hematologic blood counts, tumor markers (carcinoembryonic antigen, cancer antigen [CA] 15-5, and CA 27.29), liver ultrasonograms, or computed tomography scans. VALIDATION: The recommendations of the breast cancer expert panel were evaluated and supported by the ASCO Health Services Research Committee reviewers and the ASCO Board of Directors. (+info)
Follow-up of breast cancer in primary care vs specialist care: results of an economic evaluation.
A randomized controlled trial (RCT) comparing primary-care-centred follow-up of breast cancer patients with the current standard practice of specialist-centred follow-up showed no increase in delay in diagnosing recurrence, and no increase in anxiety or deterioration in health-related quality of life. An economic evaluation of the two schemes of follow-up was conducted concurrent with the RCT Because the RCT found no difference in the primary clinical outcomes, a cost minimization analysis was conducted. Process measures of the quality of care such as frequency and length of visits were superior in primary care. Costs to patients and to the health service were lower in primary care. There was no difference in total costs of diagnostic tests, with particular tests being performed more frequently in primary care than in specialist care. Data are provided on the average frequency and length of visits, and frequency of diagnostic testing for breast cancer patients during the follow-up period. (+info)
Cancer carve outs, specialty networks, and disease management: a review of their evolution, effectiveness, and prognosis.
Specialty care programs for patients with cancer were among the first to be developed, yet they have been some of the slowest to grow or to demonstrate success. This paper reviews the evolution of cancer carve outs, disease management, and specialty networks by distinguishing purchasers from sellers on key attributes. It also describes financing and operational impediments to their growth and summarizes what little published data there is documenting the success of these programs. The paper analyzes the critical factors impeding the development of these cancer programs, and discusses the public policy changes and health services research that will need to be conducted before the performance and market influence of cancer carve outs will reach their full potential. (+info)
Audiotapes and letters to patients: the practice and views of oncologists, surgeons and general practitioners.
A range of measures have been proposed to enhance the provision of information to cancer patients and randomized controlled trials have demonstrated their impact on patient satisfaction and recall. The current study explored the practice and views of oncologists, surgeons and general practitioners (GPs) with regards to providing patients with consultation audiotapes and summary letters. In stage 1, 28 semi-structured interviews with doctors were conducted to provide qualitative data on which to base a questionnaire. In stage 2, 113 medical oncologists, 43 radiation oncologists, 55 surgeons and 108 GPs completed questionnaires. Only one-third of doctors had ever provided patients with a copy of the letter written to the oncologist or referring doctor, and one-quarter had provided a summary letter or tape. The majority of doctors were opposed to such measures; however, a substantial minority were in favour of providing a letter or tape under certain conditions. More surgeons and GPs (> two-thirds) were opposed to specialists providing a consultation audiotape than oncologists (one-third). Gender, years of experience and attitude to patient involvement in decision-making were predictive of doctors' attitudes. The majority of doctors remain opposed to offering patients personalized information aids. However, practice and perspectives appear to be changing. (+info)
Systematic review of cancer treatment programmes in remote and rural areas.
In an attempt to ensure high quality cancer treatment for all patients in the UK, care is being centralized in specialist centres and units. For patients in outlying areas, however, access problems may adversely affect treatment. In an attempt to assess alternative methods of delivering cancer care, this paper reviews published evidence about programmes that have set out to provide oncology services in remote and rural areas in order to identify evidence of effectiveness and problems. Keyword and textword searches of on-line databases (MEDLINE, EMBASE, HEALTHSTAR and CINAHL) from 1978 to 1997 and manual searches of references were conducted. Fifteen papers reported evaluations of oncology outreach programmes, tele-oncology programmes and rural hospital initiatives. All studies were small and only two were controlled, so evidence was suggestive rather than conclusive. There were some indications that shared outreach care was safe and could make specialist care more accessible to outlying patients. Tele-oncology, by which some consultations are conducted using televideo, may be an acceptable adjunct. Larger and more methodologically robust studies are justified and should be conducted. (+info)
Improving the letters we write: an exploration of doctor-doctor communication in cancer care.
Referral and reply letters are common means by which doctors exchange information pertinent to patient care. Twenty-eight semi-structured interviews were conducted exploring the views of oncologists, referring surgeons and general practitioners. Twenty-seven categories of information in referral letters and 32 in reply letters after a consultation were defined. The letters to and from six medical oncologists relating to 20 consecutive new patients were copied, and their content analysed. Oncologists, surgeons and general practitioners Australia wide were surveyed using questionnaires developed on data obtained above. Only four of 27 categories of referral information appear regularly (in > 50%) in referral letters. Oncologists want most to receive information regarding the patient's medical status, the involvement of other doctors, and any special considerations. Referring surgeons and family doctors identified delay in receiving the consultant's reply letter as of greatest concern, and insufficient detail as relatively common problems. Reply letters include more information regarding patient history/background than the recipients would like. Referring surgeons and family doctors want information regarding the proposed treatment, expected outcomes, and any psychosocial concerns, yet these items are often omitted. Consultants and referring doctors need to review, and modify their letter writing practices. (+info)