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Biomedical subjects

Ian Quirt

Publications and source records attributed to Ian Quirt.

8 recordsLinked to original sources
PubMed2006

Systematic review of systemic adjuvant therapy for patients at high risk for recurrent melanoma.

The authors examined the role of systemic adjuvant therapy in patients with high-risk, resected, primary melanoma. Outcomes of interest included overall survival, disease-free survival, adverse effects, and quality of life. A systematic review of the literature was conducted to locate randomized controlled trials, practice guidelines, meta-analyses, and reviews published between 1980 and 2004. Thirty-seven randomized controlled trials, 2 meta-analyses, and 1 systematic review were identified that investigated interferon, levamisole, vaccine, or chemotherapy as adjuvant therapy. For high-dose interferon-alpha, the results from 3 randomized trials conducted by the Eastern Cooperative Oncology Group were pooled, and a meta-analysis of 2-year death rates yielded a risk ratio of 0.85 (95% confidence interval, 0.73-0.99; P = .03). Five randomized trials comparing low-dose interferon-alpha with observation only after surgery did not detect a statistically significant improvement in overall survival. A meta-analysis of 4 levamisole trials did not demonstrate a significant survival benefit for levamisole over control; similarly, no survival benefit was demonstrated by data from randomized controlled trials with vaccines (9 trials) or with chemotherapy (10 trials). In this review of the available literature, no systemic adjuvant therapy was identified that conferred a significant overall survival benefit in patients with high-risk, resected, primary melanoma. However, high-dose interferon should be considered in the treatment of these patients, because such therapy is associated with a significant improvement in disease-free survival and a reduction in 2-year mortality. Until the results of ongoing trials are available, the authors could not state with confidence whether such therapy benefits patients with microscopically detected, sentinel lymph node-positive disease.

Adjuvants, Immunologic↗
PubMed2006

Intravenous iron and recombinant erythropoietin for the treatment of postoperative anemia.

PURPOSE: To determine if early recovery from severe post-operative anemia is accelerated by iv iron therapy alone or in combination with recombinant erythropoietin (EPO). METHODS: In this double-blinded, placebo-controlled randomized study, consenting adult patients without preoperative anemia whose hemoglobin concentration (Hb) was 70 to 90 g x L(-1) on the first day after cardiac or orthopedic surgery (POD 1) were assigned to one of three groups: control, iv iron alone (200 mg of iron sucrose on POD 1, 2, and 3) or in combination with EPO (600 U x kg(-1) on POD 1 and 3). The primary outcome was increase in Hb (adjusted for red blood cell transfusions) from POD 1 to 7. Analysis was by intention-to-treat in patients for whom the primary outcome was available. Group effect was analyzed by the ANOVA test, and between-group differences were specified with a Duncan multiple-range test. RESULTS: The primary outcome was available in 31 of 38 randomized patients. The average POD 1 Hb was 84 +/- 4 g x L(-1). There were no between-group differences in outcomes except for higher reticulocyte counts on POD-7 in the combination group. The average adjusted one-week increases in Hb were 7 +/- 8 g x L(-1) in the control group (n = 10), 9 +/- 9 g x L(-1) in the iv iron group (n = 11), and 10 +/- 14 g x L(-1) in the combination group (n = 10). The average adjusted six-week increases in Hb were 37 +/- 14 g x L(-1) in the control group, 40 +/- 7 g x L(-1) in the iv iron group, and 45 +/- 12 g x L(-1) in the combination group. CONCLUSION: Early postoperative treatment with iv iron alone or in combination with EPO does not appear to accelerate early recovery from postoperative anemia.

Analysis of Variance↗
PubMed2006

Patients previously transfused or treated with epoetin alfa at low baseline hemoglobin are at higher risk for subsequent transfusion: an integrated analysis of the Canadian experience.

BACKGROUND: The introduction of recombinant human erythropoietin to the management of anemia in cancer patients has resulted in significant reductions in allogeneic blood transfusions, while at the same time contributing to improvements in quality of life. A recent meta-analysis of five randomized, placebo-controlled trials with patient-level data revealed that, while epoetin alfa was very effective in reducing transfusions compared with placebo, patients who were pretransfused were twice as likely to subsequently be transfused during epoetin alfa treatment. METHODS: To further assess the validity of this rather provocative concept, another integrated analysis was conducted with patient-level data from three Canadian trials, with a combined total of 665 patients receiving epoetin alfa treatments for their cancer- and chemotherapy-induced anemia. RESULTS: Once again, pretransfusion was the most significant baseline predictor of transfusion, with patients that were pretransfused having a significantly greater likelihood of being transfused than their transfusion-naive counterparts. Furthermore, and corroborating previous findings, baseline hemoglobin (Hb) level was again found to be a significant predictor of transfusion, with patients who were treated at a baseline Hb level < 10 g/dl having a higher chance of being transfused than patients in whom epoetin alfa was initiated at baseline Hb levels of 10-11 g/dl. In addition, when the total units transfused in patients receiving epoetin alfa at different baseline Hb levels were analyzed, >85% of the units of blood transfused were received by patients with baseline Hb levels < 10 g/dl. CONCLUSION: These data strongly suggest that early treatment with epoetin alfa could significantly optimize clinical benefit in reducing the use of transfusion in cancer patients receiving chemotherapy.

Adolescent↗
PubMed2005

CCI-779 in metastatic melanoma: a phase II trial of the California Cancer Consortium.

BACKGROUND: CCI-779 is an analog of the immunosuppressive agent, rapamycin, that has demonstrated activity against melanoma in preclinical models and shown clinical benefit in patients with breast and renal carcinoma. CCI-779 is not immunosuppressive when administered on an intermittent schedule, and its toxicity is modest, consisting of nausea, diarrhea, hypertriglyceridemia, thrombocytopenia, asthenia, and follicular dermatitis. METHODS: The current trial was designed to detect a median time to disease progression of >18 weeks in patients with metastatic melanoma treated with a 250-mg weekly dose of CCI-779 administered intravenously after diphenhydramine premedication. Patients with measurable disease, no more than one previous chemotherapy regimen for metastatic disease, and normal organ function were eligible, and patients with central nervous system involvement, P450-inducing or P450-suppressing drugs, or hypertriglyceridemia were excluded. RESULTS: Thirty-three patients (21 males) were treated, 21 of whom had been treated previously with chemotherapy and/or biologic agents for advanced-stage disease. One patient had a partial response lasting 2 months. The median time to disease progression and overall survival were 10 weeks and 5 months, respectively. Toxicity was mild and predominantly mucocutaneous (stomatitis, diarrhea, and rash). Hyperlipidemia was cumulative and was managed with lipid-lowering agents. CONCLUSIONS: CCI-779 was not sufficiently active in melanoma to warrant further testing as a single agent.

Adult↗
PubMed2004

Phase II trial of flavopiridol, a cyclin dependent kinase inhibitor, in untreated metastatic malignant melanoma.

PURPOSE: To test the activity of the cyclin dependent kinase (cdk) inhibitor flavopiridol in malignant melanoma, a disease with frequent abnormalities of the cyclin dependent kinase system. PATIENTS AND METHODS: Patients had histologically proven, unidimensionally measurable malignant melanoma, incurable by standard therapy. Prior adjuvant immunotherapy was allowed, but patients were otherwise untreated for advanced disease. Flavopiridol was administered at a dose of 50 mg/m(2) IV over 1 hour daily x 3 days every 3 weeks. Patients were assessed for response every 2 cycles. RESULTS: 17 patients were accrued over 5 months. No objective responses were documented in the 16 patients evaluable for response. Seven patients (44%) had stable disease after 2 cycles, with a median of 2.8 months (range 1.8-9.2). The most common treatment-related non-hematologic toxicities were diarrhea (82%), nausea (47%), fatigue (41%), anorexia (35%) and vomiting (29%). Most treatment-related toxicities were mild, except for diarrhea (grade 3 in 3 patients, grade 4 in 1 patient), nausea (grade 3 in 1 patient) and tumor pain (grade 3 in 1 patient). Hematologic toxicities were minimal, none worse than grade 2. Eighty-eight percent of patients received >/=90% planned dose intensity; 2 patients had dose reductions for gastrointestinal (GI) toxicity. CONCLUSIONS: Flavopiridol is well tolerated at the dose regimen used in this study, with an acceptable (primarily GI) toxicity profile. Although 7 of the 16 patients had stable disease ranging from 1.8 to 9.2 months in duration, there was no evidence of significant clinical activity in malignant melanoma by objective response criteria.

Adult↗
PubMed2002

Phase II study of marimastat (BB-2516) in malignant melanoma: a clinical and tumor biopsy study of the National Cancer Institute of Canada Clinical Trials Group.

OBJECTIVES: To determine the tolerability and efficacy of daily oral marimastat (BB-2516 in patients with metastatic melanoma and to determine the matrix metalloproteinase (MMP) activity, tumour necrosis, peri- and intra-tumoral fibrosis and tumor inflammation in pre- and post-treatment tumor biopsies. PATIENTS AND METHODS: Patients with measurable metastatic melanoma who had received no more than one prior chemotherapy regimen and lesions accessible for biopsy were eligible. The first 18 were treated with 100 mg p.o. twice daily and the next 11 received a reduced dose of 10 mg p.o. twice daily because of musculoskeletal toxicity. Response was assessed according to standard criteria. RESULTS: Twenty-nine patients were entered and 28 were eligible. Five had early progression (< 4 weeks of therapy), 2 experienced a partial responses persisting for 3.2 months and 3.6 months, 5 had stable disease and 16 progressive disease. Eleven patients had both pre- and post-treatment biopsies. In 3, no tumor tissue was present in one or the other biopsy. Two patients showed a clear increase in peri-tumoral fibrosis and two others showed an increase in tumor necrosis, but no consistent pattern in histologic changes was seen. In one patient, who later developed a PR, apoptosis was increased. CONCLUSION: Marimastat has only limited activity in patients with metastatic malignant melanoma. However, the observation of two partial responses was interesting given that this agent might have been expected to cause tumor stasis rather than regression. Additional studies will be required to determine if the development of peri-tumoral fibrosis or tumor necrosis antedates a clinical response to marimastat.

Adult↗
PubMed2002

Epoetin alfa in patients not on chemotherapy - Canadian data.

A prospective open-label study was designed to evaluate the safety, efficacy, and impact on quality of life of recombinant human erythropoietin (rHuEPO, epoetin alfa) therapy for cancer-related anemia. Of the 401 patients enrolled at 34 centers from across Canada, a cohort of 183 patients did not receive chemotherapy during the 16-week study period. All patients received epoetin alfa 150 IU/kg subcutaneously 3 times per week. The dose was increased to 300 IU/kg if the hemoglobin level did not increase by at least 1.0 g/dL after 4 weeks. Epoetin alfa therapy significantly increased hemoglobin levels and reduced transfusion requirements. Moreover, epoetin alfa provided statistically significant and clinically meaningful improvements in quality of life as measured by the Functional Assessment of Cancer Therapy-Anemia and Linear Analog Scale Assessment (also known as Cancer Linear Analog Scale). Increases in hemoglobin were correlated significantly with improvements in quality of life as well as Eastern Cooperative Oncology Group performance status. Treatment with epoetin alfa was well tolerated. These results demonstrate that epoetin alfa therapy is effective and safe in cancer patients with anemia, regardless of whether they are or are not receiving chemotherapy.

Aged↗