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Richard Kefford

Publications and source records attributed to Richard Kefford.

6 recordsLinked to original sources
PubMed2006

A phase II study of bosentan, a dual endothelin receptor antagonist, as monotherapy in patients with stage IV metastatic melanoma.

There is no effective systemic therapy for disseminated metastatic melanoma. Data suggest that endothelin may play a role in pathophysiology of melanoma and that the dual endothelin receptor antagonist bosentan may have anti-tumor activity. This multicenter, open-label, single-arm, prospective, proof-of-concept study assessed the effects of bosentan monotherapy (500 mg oral tablets, bid) on tumor response in patients with stage IV metastatic melanoma. Patients were treated until disease progression, death or serious adverse event leading to premature study drug discontinuation. Tumor response was assessed at 6-weekly intervals using the Response Evaluation Criteria in Solid Tumors (RECIST). Among the 35 patients included in this study with stage IV metastatic melanoma, 21 (60%) were stage M1C, 10 (29%) stage M1B and 4 (11%) stage M1A (American Joint Committee on Cancer [AJCC] classification). Nine patients (26%) had received prior therapy for stage IV melanoma. Disease stabilization was observed in 6 of the 32 patients analyzed per protocol at week 6 with confirmatory evaluation at week 12, 5 of whom were still stable at > or =24 weeks. Of the 6 patients with disease stabilization, 2 were stage M1A, 1 was stage M1B and the remaining 3 were stage M1C. Partial or complete response was not observed. Progressive disease was observed in 17 (49%) patients at week 12 and in 25 (71%) patients at the end of the study (data base closure). The most frequent adverse events were typical for the underlying disease or known to be associated with bosentan: headache (43%), fatigue (34%), nausea (31%), back pain (23%) and abnormal hepatic function (23%). Bosentan might have benefit in disease stabilization in certain patients with metastatic melanoma and deserves further investigation in combination with other anticancer drugs.

Administration, Oral↗
PubMed2006

Association between circulating white blood cell count and cancer mortality: a population-based cohort study.

BACKGROUND: Inflammatory processes are implicated in the development and progression of cancer. However, it is not clear whether systemic markers of inflammation predict cancer. We examined the prospective relationship between circulating white blood cell (WBC) count and cancer mortality. METHODS: Population-based cohort study of 3189 individuals, aged 49 to 84 years and free of cancer at the baseline examination (January 1, 1992, to December 31, 1994), in the Blue Mountains region, west of Sydney, Australia. The main outcome of interest was all cancer mortality ascertained from vital status as of December 31, 2001. RESULTS: Higher WBC count was found to be associated with all cancer mortality. In proportional hazards models adjusting for age, sex, education, body mass index, hematocrit level, alcohol consumption, physical inactivity, smoking, weekly aspirin use, diabetes mellitus or fasting hyperglycemia status, and fasting glucose levels, the multivariable relative risk of all cancer mortality comparing quartile 4 of WBC count ( > or = 7400 cells/microL) with quartile 1 (< or = 5300 cells/microL) was 1.73 (95% confidence interval [CI], 1.18-2.55). In subgroup analyses, the relative risk of cancer mortality comparing quartile 4 of WBC count with quartile 1 was higher among those with diabetes or fasting hyperglycemia (3.03 [95% CI, 1.01-9.15]) than among those with normoglycemia (1.68 [95% CI, 1.12-2.52]). Also, the relative risk of cancer mortality associated with joint exposure to quartile 4 of WBC count and aspirin nonuse was 2.42 (95% CI, 1.46-4.01) compared with their absence. CONCLUSION: These data provide new epidemiological evidence of an association between circulating WBC count, a widely available marker of inflammation, and subsequent cancer mortality.

Aged↗
PubMed2005

Locally advanced and inflammatory breast cancer.

This tenth article in our series on breast disease focuses on locally advanced breast cancer and inflammatory breast cancer -- both associated with a high risk of subsequent distant metastases.

Antineoplastic Agents↗
PubMed2003

Patterns of metastases in familial and non-familial melanoma.

Family history is a strong risk factor for the development of primary melanoma and is associated in a subset with inherited mutations in melanoma susceptibility genes. This study sought to determine whether differences in metastatic pattern exist between patients with a positive family history (FH+) and those with a negative family history (FH-). Such differences could have importance for clinical management and in the determination of the function of both known and putative melanoma susceptibility genes. A retrospective, nested case-controlled study was performed. Of the FH+ cohort (n = 38), 26 were from kindreds with two histologically verified affected first-degree relatives and 12 were from kindreds with three or more affected members, at least two of whom were first-degree relatives. Three FH- controls from the Sydney Melanoma Unit database were matched to each case for age, sex, stage at diagnosis, number of primary melanomas and year of diagnosis (n = 114). There were no statistically significant differences between the two groups with regard to overall survival from initial diagnosis (FH+, 57.4 months; FH-, 50.0 months; P = 0.99), median survival from time of first metastasis (FH+, 15.4 months; FH-, 15.9 months; P = 0.94), or median disease-free interval (FH+, 26.4 months; FH-, 29.7 months; P = 0.73). On multivariate conditional logistic regression analysis, there was no statistically significant difference between the two groups in the probability of developing initial metastases or of ever developing metastases at specific sites. Survival, disease-free interval and distribution of metastatic sites are similar in both familial and non-familial melanoma. Genetic susceptibility for melanoma may lower the threshold for entering an otherwise common molecular pathway for tumour development and evolution.

Adolescent↗