Biomedical subjects

David H Lawson

Publications and source records attributed to David H Lawson.

8 recordsLinked to original sources

PubMed2007

Interferon Alfa-2b or not 2b? Significant differences exist in the decision-making process between melanoma patients who accept or decline high-dose adjuvant interferon Alfa-2b treatment.

BACKGROUND: Patients with thick (Breslow>4 mm) primary melanoma and/or regional nodal metastasis have a high risk of tumor recurrence. High-dose adjuvant interferon (IFN) alfa-2b offers /=50% risk of recurrence/disease-related mortality and offered IFN. Telephone surveys delineated reasons behind patients' decisions to accept IFN. RESULTS: Acceptors, 60 of 135 (45%), decided to take IFN alfa-2b whereas 75 of 135 (55%) declined. Being female (OR, 2.4; 95% CI, 1.17-5.03; p=.017) and positive SLN status (OR, 2.2; 95% CI, 1.01-4.97; p=.048) were strongly associated with patients who chose IFN. Acceptors of IFN were younger, more influenced by physicians, and less affected by depression and side effect profile (p<.05 for all). Decliners were more concerned by strained relationships with family and social life (p<.05). CONCLUSIONS: Gender and positive SLN were predictive of high-risk melanoma patients' acceptance of IFN treatment. Physician insight into melanoma patients' therapeutic decision-making process can guide patients through this difficult disease.

Adult↗

PubMed2005

Choices in adjuvant therapy of melanoma.

BACKGROUND: High-dose interferon (IFN) is the approved agent for adjuvant treatment of melanoma in the United States. This approval is for high-risk, predominantly stage III patients with cutaneous primaries. There are still decisions to be made in the care of these patients. Also, there are questions about whether the IFN data can be extrapolated to patients with other stages of melanoma and whether adjuvant treatment should be offered to these individuals. Clearly there is room for improvement in this area. METHODS: The literature on this topic and ongoing national trials in the United States were reviewed. RESULTS: The data are insufficient to recommend other agents in the adjuvant treatment of melanoma outside a clinical trial. Extrapolation of the IFN data to patient populations other than those studied is problematic at best. National trials are available for most patient populations. CONCLUSIONS: The adjuvant treatment of choice for melanoma patients is participation in a clinical trial.

Antineoplastic Agents↗

PubMed2004

Update on the systemic treatment of malignant melanoma.

The purpose of this article is to review some of the recent advances and disappointments in the systemic treatment of melanoma and to highlight some of the ongoing trials in this area. Two major advances in the staging of melanoma are the new American Joint Committee on Cancer staging system and the use of the sentinel node biopsy. Interferon remains the standard adjuvant therapy for high-risk patients. Ongoing trials are evaluating 1 month of high-dose interferon versus observation in intermediate-risk patients and comparing standard interferon with biochemotherapy. Allogeneic and peptide vaccines and granulocyte-macrophage colony-stimulating factor are also being evaluated. Dacarbazine and high-dose IL-2 are the only US Food and Drug Administration approved systemic treatments for stage IV disease. Several new agents are being evaluated. Melanoma remains a prototype disease in which patients should be encouraged to participate in clinical trials.

Antineoplastic Agents↗

PubMed2004

Plasma homocysteine and immune activation in patients with malignant melanoma undergoing treatment with IFN-alpha.

Immune activation and cell proliferation may contribute to the development of increased homocysteine concentrations in patients with malignant diseases. In this study, we investigated the effect of interferon-alpha (IFN-alpha) on plasma homocysteine concentrations in patients being treated for malignant melanoma. In parallel, neopterin formation and tryptophan degradation were monitored to assess the capacity of IFN-alpha to activate macrophages. Plasma concentrations of homocysteine, folate, and vitamin B(12) were determined in 15 patients with malignant melanoma during 12 weeks of high-dose IFN-alpha therapy. Concurrently, concentrations of neopterin, tryptophan, and kynurenine were measured, and the kynurenine/tryptophan ratio (kyn/trp) was calculated. Homocysteine and folate concentrations during treatment with IFN-alpha did not differ from baseline. In contrast, significant increases in neopterin formation and tryptophan degradation were apparent during IFN-alpha therapy. Plasma concentrations of vitamin B(12) and cysteine also increased. These results indicate that IFN-alpha directly activates macrophages to release neopterin and to degrade tryptophan, but obviously treatment with INF-alpha did not affect homocysteine metabolism.

Adult↗

PubMed2003

Interferon-alpha-induced changes in tryptophan metabolism. relationship to depression and paroxetine treatment.

BACKGROUND: Tryptophan (TRP) degradation into kynurenine (KYN) by the enzyme, indoleamine-2,3-dioxygenase, during immune activation may contribute to development of depressive symptoms during interferon (IFN)-alpha therapy. METHODS: Twenty-six patients with malignant melanoma were randomly assigned in double-blind fashion to receive either placebo or paroxetine, beginning 2 weeks before IFN-alpha treatment and continuing for the first 12 weeks of IFN-alpha therapy. At treatment initiation and at 2, 4, and 12 weeks of IFN-alpha treatment, measurements of TRP, KYN, and neopterin (a marker of immune activation), were obtained, along with structured assessments of depression, anxiety, and neurotoxicity. RESULTS: Regardless of antidepressant treatment status, all patients exhibited significant increases in KYN, neopterin, and the KYN/TRP ratio during IFN-alpha therapy. Among antidepressant-free patients, patients who developed major depression exhibited significantly greater increases in KYN and neopterin concentrations and more prolonged decreases in TRP concentrations than did nondepressed, antidepressant-free patients. Moreover, in antidepressant-free patients, decreases in TRP correlated with depressive, anxious, and cognitive symptoms, but not neurovegetative or somatic symptoms. No correlations were found between clinical and biological variables in antidepressant-treated patients. CONCLUSIONS: The results suggest that reduced TRP availability plays a role in IFN-alpha-induced depressive symptoms, and paroxetine, although not altering the KYN or neopterin response to IFN-alpha, attenuates the behavioral consequences of IFN-alpha-mediated TRP depletion.

Adult↗

PubMed2003

Association of exaggerated HPA axis response to the initial injection of interferon-alpha with development of depression during interferon-alpha therapy.

OBJECTIVE: The authors assessed the relationship between the hypothalamic-pituitary-adrenal (HPA) axis response to interferon-alpha (IFN-alpha) and the development of major depression during IFN-alpha treatment. METHOD: Adrenocorticotropic hormone (ACTH), cortisol, and interleukin-6 (IL-6) plasma concentrations were measured in 14 patients with malignant melanoma at regular intervals during the first 12 weeks of IFN-alpha therapy, both immediately before and 1, 2, and 3 hours after IFN-alpha administration. Symptom criteria for major depression were also evaluated at each visit. RESULTS: ACTH and cortisol responses but not IL-6 responses to the initial administration of IFN-alpha were significantly higher in the seven patients who subsequently developed symptom criteria for major depression than in those who did not. No differences in hormonal or cytokine responses were found between these two groups during chronic IFN-alpha administration. CONCLUSIONS: The HPA axis response to the acute administration of IFN-alpha reveals a vulnerability to IFN-alpha-induced depression, possibly due to sensitization of corticotropin-releasing factor pathways.

Adrenocorticotropic Hormone↗

PubMed2002

Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions.

We have previously shown that the risk of major depression in patients with malignant melanoma undergoing interferon-alpha (IFN-alpha) therapy can be reduced by pretreatment with the antidepressant, paroxetine. Using dimensional analyses, the present study assessed the expression and treatment responsiveness of specific clusters of neuropsychiatric symptoms over the first three months of IFN-alpha therapy. Forty patients with malignant melanoma eligible for IFN-alpha treatment were randomly assigned to receive either paroxetine or placebo in a double-blind design. Neuropsychiatric assessments were conducted at regular intervals during the first twelve weeks of IFN-alpha therapy and included the 21-item Hamilton Depression Rating Scale, the 14-item Hamilton Anxiety Rating Scale and the Neurotoxicity Rating Scale. Neurovegetative and somatic symptoms including anorexia, fatigue and pain appeared within two weeks of IFN-alpha therapy in a large proportion of patients. In contrast, symptoms of depressed mood, anxiety and cognitive dysfunction appeared later during IFN-alpha treatment and more specifically in patients who met DSM-IV criteria for major depression. Symptoms of depression, anxiety, cognitive dysfunction and pain were more responsive, whereas symptoms of fatigue and anorexia were less responsive, to paroxetine treatment. These data demonstrate distinct phenomenology and treatment responsiveness of symptom dimensions induced by IFN-alpha, and suggest that different mechanisms mediate the various behavioral manifestations of cytokine-induced "sickness behavior."

Adult↗

PubMed2002

Melanoma growth stimulatory activity in primary malignant melanoma: prognostic significance.

Malignant melanoma (MM) cells do not require all exogenous growth factors of normal melanocytes. It is hypothesized that they make their own growth factors including melanoma growth stimulatory activity (MGSA). Cultured melanoma cells respond to MGSA with increased growth and angiogenesis suggesting a role for MGSA in MM proliferation, differentiation, and progression. We assessed the prognostic significance of MGSA expression in 37 primary MM immunostained for MGSA. Immunostains were graded for intensity (0-3+), percentage of cells immunostained, and location of immunostain (intraepidermal, junctional, or dermal). In addition, 31 melanocytic and 23 dysplastic nevi were similarly studied for MGSA expression. All MM showed the presence of immunostain, 6 (16%) 1+, 12 (32%) 2+, and 19 (51%) 3+. Six (16%) had immunostain in < or = 50% tumor cells, 31 (84%) in >50%. A significant number of MM showed >50% tumor cells staining at the dermal-epidermal junction compared with intraepidermal staining (P <.0001). Intensity and amount of immunostain did not correlate with Clark's or Breslow's level. During a mean follow-up of 60 months (range: 5-101) on 27 patients, there were 4 local recurrences, 6 distant metastases, and 10 deaths. MGSA expression was not of prognostic significance with regard to survival (overall, disease free), or local recurrence or distant metastasis in primary MM. MGSA expression was similar in benign melanocytic and dysplastic nevi. Strong diffuse expression was noted in the junctional component of all junctional and most compound nevi. The dermal component consistently expressed less or no (in 45% of intradermal nevi) MGSA. MGSA expression does not correlate with prognosis in MM. Increased expression of MGSA at the dermal-epidermal junction in nevi and MM may indicate a role for MGSA in early local growth, before development of atypia.

Adolescent↗