Biomedical subjects

Dorothy Keefe

Publications and source records attributed to Dorothy Keefe.

10 recordsLinked to original sources

PubMed2006

Palifermin for oral mucositis in the high-dose chemotherapy and stem cell transplant setting: the Royal Adelaide Hospital Cancer Centre experience.

GOALS OF WORK: the aim of this paper was to review the initial use of Palifermin(rHu-KGF1) in a single institution, for the prevention of oral mucositis in high-dose chemotherapy and stem cell transplantation. METHODS: the case records of the first five patients treated with Palifermin at the Royal Adelaide Hospital Cancer Centre were reviewed, and incidence,severity and duration of the oral mucositis were recorded, as well as demographics and toxicities. RESULTS: two of the five patients developed grade 4 mucositis, and the remaining three patients developed grade 2 mucositis. Palifemin was well tolerated with only one patient developing a rash. CONCLUSIONS: the severity of oral mucositis was less than would be expected in these patients without anti-mucositis therapy. Palifermin was well tolerated. Obviously this single institution report is from a very small cohort of patients, but it is encouraging for the ease of use of this drug in the future.

Adult↗

PubMed2006

Growth factors and cytokines in the prevention and treatment of oral and gastrointestinal mucositis.

GOALS OF WORK: Growth factors and cytokines may be useful in preventing chemotherapy (CT)- and radiotherapy (RT)-induced oral and gastrointestinal mucositis. Two systematic reviews of the medical literature on growth factors and cytokines for the amelioration of CT- and RT-induced mucositis throughout the alimentary tract were performed by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology. The aim of these evidence-based scientific reviews was to critically evaluate the literature and create evidence-based guidelines for the use of growth factors and cytokines in the prevention or treatment of CT- and RT-induced mucositis. METHOD: The two reviews covered articles on clinical trials from January 1966 through May 2002 and preclinical studies from June 2002 through May 2005, respectively. The systematic review process was based on a well-established method for evaluating scientific literature. MAIN RESULTS: The number of articles in the first review was 29. In the second review, 23 articles were evaluated, 14 preclinical and 9 clinical studies. It was concluded from the first review that there was no sufficient evidence to provide any recommendations for clinical practice guidelines regarding growth factors and cytokines. From the second review, a guideline could be presented recommending the use of recombinant human keratinocyte growth factor-1 (palifermin) to prevent oral mucositis in patients receiving high-dose CT and total body irradiation followed by stem cell transplantation for haematological malignancies. A guideline could also be provided suggesting that granulocyte macrophage colony-stimulating factor mouthwash not be used for the prevention of oral mucositis in the transplant setting with high-dose CT and autologous or allogeneic stem cell transplantation. CONCLUSIONS: These systematic reviews have provided clarity and shown exciting new results. Further studies will provide new options for this debilitating side-effect of cancer therapy.

Animals↗

PubMed2006

Alimentary mucositis: putting the guidelines into practice.

BACKGROUND: The Mucositis Study Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology completed an evidence-based review of the literature for the management of alimentary mucositis. DISCUSSION: The present manuscript puts these guidelines into clinical practice by presenting two cases of alimentary mucositis from cancer therapy. These cases illustrate the impact of oral and gastrointestinal mucositis on patient care.

Antineoplastic Agents↗

PubMed2006

Amifostine in the management of radiation-induced and chemo-induced mucositis.

INTRODUCTION: Mucositis is a significant complication of cancer therapy, with important clinical and economic implications. In June 2005, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) conducted an evidence-based update review of the literature on mucositis. The goal of this literature review is to update previously published guidelines for the management of mucositis. RESULTS: This article reports the findings of the subgroup charged with reviewing the literature related to amifostine.

Amifostine↗

PubMed2006

Anti-inflammatory agents in the management of alimentary mucositis.

BACKGROUND: Alimentary mucositis is a significant complication of cancer therapy, with important clinical and economic implications. MATERIALS AND METHODS: In June 2005, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology conducted an evidence-based review of the literature on alimentary mucositis. The goal of this literature review was to update previously published guidelines for the management of mucositis. RESULTS: This article reports the findings of the subgroup charged with reviewing the literature related to anti-inflammatory interventions. Considerable preclinical and clinical evidence suggests that the use of anti-inflammatory agents may be a promising approach to reduce the severity of mucositis. However, there was not enough evidence to support any new guidelines advocating the use of any specific anti-inflammatory intervention. CONCLUSION: Thus, there is a need for well-designed clinical trials evaluating the use of anti-inflammatory agents in the management of mucositis.

Allopurinol↗

PubMed2006

Radiation therapy-induced mucositis: relationships between fractionated radiation, NF-kappaB, COX-1, and COX-2.

Radiation therapy is one of the three major treatment modalities used in eradicating malignant tumours. When ionising radiation is used to treat abdominal tumours, severe side effects largely due to mucosal damage in the alimentary tract are common, particularly when it is combined with chemotherapy. Radiation-induced mucositis may not only limit the therapeutic doses of combined treatment but also adversely affect the quality of life of the patient. Treatment strategies to treat and prevent radiation-induced mucositis have been reviewed and published in the Clinical Practice Guidelines, 2004. However evidence supporting an effective treatment approach is tenuous, probably because the mechanistic evolution of radiation-induced mucositis is poorly understood. Several animal models have been used to examine the various effects of radiation but no single animal model has been able to effectively capture the effects of radiation on the alimentary tract at the molecular level before symptoms begin. This review will outline the events which occur following radiation exposure; from chromosomal aberrations in the mucosal cells leading to apoptotic and mitotic death, to the evolution of mucositis involving changes in gene activations and signaling. A better understanding of the mechanisms of radiation therapy-induced mucositis is necessary as it will allow for future pharmaceutical interventions to alleviate if not eliminate the debilitating side effects.

Cyclooxygenase 1↗

PubMed2005

A phase I study of prolonged ambulatory infusion of Ifosfamide with oral mesna.

BACKGROUND: Oral mesna allows investigation of ifosfamide as a prolonged ambulatory infusion for dose-intense out-patient use. METHODS: Cohorts of 3 patients received escalating doses of ifosfamide from 200 to 1,000 mg/m2/day as continuous ambulatory infusion with oral mesna at 30% of the ifosfamide dose every 6 h commencing 2 h prior to ifosfamide infusion as uroprotection on a 14-day schedule with cycles repeated every 28 days. RESULTS: Fifteen patients received a median of three cycles. Dose-limiting toxicities with cycle 1 were lethargy and hepatotoxicity at 1,000 mg/m2/14 days. Transient transaminase elevation was seen at all dose levels. The other grade 3 toxicities were single episodes of anaemia, granulocytopenia, nausea and hypotension. The best response was stable disease in a patient with thyroid cancer. CONCLUSION: Ambulatory infusion of 600 mg/m2 ifosfamide with 180 mg/m2 oral mesna was considered suitable for phase II trials and delivers dose-intense out-patient therapy without urotoxicity.

Administration, Oral↗

PubMed2004

Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients.

BACKGROUND: A frequent complication of anticancer treatment, oral and gastrointestinal (GI) mucositis, threatens the effectiveness of therapy because it leads to dose reductions, increases healthcare costs, and impairs patients' quality of life. The Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an international multidisciplinary panel of experts to create clinical practice guidelines for the prevention, evaluation, and treatment of mucositis. METHODS: The panelists examined medical literature published from January 1966 through May 2002, presented their findings at two separate conferences, and then created a writing committee that produced two articles: the current study and another that codifies the clinical implications of the panel's findings in practice guidelines. RESULTS: New evidence supports the view that oral mucositis is a complex process involving all the tissues and cellular elements of the mucosa. Other findings suggest that some aspects of mucositis risk may be determined genetically. GI proapoptotic and antiapoptotic gene levels change along the GI tract, perhaps explaining differences in the frequency with which mucositis occurs at different sites. Studies of mucositis incidence in clinical trials by quality and using meta-analysis techniques produced estimates of incidence that are presented herein for what to our knowledge may be a broader range of cancers than ever presented before. CONCLUSIONS: Understanding the pathobiology of mucositis, its incidence, and scoring are essential for progress in research and care directed at this common side-effect of anticancer therapies.

Antineoplastic Agents↗

PubMed2004

Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis.

BACKGROUND: Oral and gastrointestinal (GI) mucositis can affect up to 100% of patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation, 80% of patients with malignancies of the head and neck receiving radiotherapy, and a wide range of patients receiving chemotherapy. Alimentary track mucositis increases mortality and morbidity and contributes to rising health care costs. Consequently, the Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an expert panel to evaluate the literature and to create evidence-based guidelines for preventing, evaluating, and treating mucositis. METHODS: Thirty-six panelists reviewed literature published between January 1966 and May 2002. An initial meeting in January 2002 produced a preliminary draft of guidelines that was reviewed at a second meeting the same year. Thereafter, a writing committee produced a report on mucositis pathogenesis, epidemiology, and scoring (also included in this issue), as well as clinical practice guidelines. RESULTS: Panelists created recommendations from higher levels of evidence and suggestions when evidence was of a lower level and there was a consensus regarding the interpretation of the evidence by the panel. Panelists identified gaps in evidence that made it impossible to recommend or not recommend use of specific agents. CONCLUSIONS: Oral/GI mucositis is a common side effect of many anticancer therapies. Evidence-based clinical practice guidelines are presented as a benchmark for clinicians to use for routine care of appropriate patients and as a springboard to challenge clinical investigators to conduct high-quality trials geared toward areas in which data are either lacking or conflicting.

Antineoplastic Agents↗

PubMed2002

A phase I study of the GM-CSF antagonist E21R.

PURPOSE: E21R is a competitive inhibitor of GM-CSF. This is the initial clinical study to investigate the safety, toxicity and pharmacokinetics of escalating doses of E21R. PATIENTS AND METHODS: Cohorts of three patients received doses of 10, 30, 100, 300, 600 and 1000 micro g/kg per day given subcutaneously daily for 10 days. Eligible patients had solid tumours known to express GM-CSF receptors (breast, prostate, colon and lung cancer, and melanoma). No bone marrow involvement or concomitant steroids were permitted. A total of 22 patients received doses ranging from 10 to 1000 micro g/kg per day. There were 18 males and 4 females with a median age of 60 years (range 33 to 81 years). Eight patients had an ECOG performance status of 0, seven a performance status of 1, and seven a performance status of 2. There were ten patients with colon cancer, four with prostate cancer, three with lung cancer, three with melanoma and two with breast cancer. RESULTS: E21R was in general well tolerated and the maximum tolerated dose was not reached. The most severe toxicities were WHO grade 3 injection site erythema in one patient and grade 2 in two patients, grade 2 lethargy in three patients and grade 2 muscle aches and soreness, grade 2 joint pains and grade 2 thirst in one patient each. The primary pharmacokinetic parameters were dose-independent. Dose-dependent transient eosinophilia was noted from day 3. A fall in PSA levels was recorded in two patients with prostate cancer during their initial cycles of E21R, but they subsequently rose again. Serum from patients treated at 600 and 1000 micro g/kg per day antagonized GM-CSF-mediated TF-1 cell proliferation in vitro. CONCLUSION: E21R can be safely given at doses up to 1000 micro g/kg per day.

Adult↗