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Justin Stebbing

Publications and source records attributed to Justin Stebbing.

At least 19 recordsLinked to original sources
PubMed2007

Efficacy and safety of first- or second-line irinotecan, cisplatin, and mitomycin in mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rapidly progressive lethal tumor. Treatment options remain limited and the outcome in recurrent disease is poor. METHODS: A Phase II open-label noncomparative study was conducted to assess the safety and efficacy of the triplet combination irinotecan, cisplatin, and mitomycin-C (IPM) chemotherapy in untreated patients and in those with previous exposure to chemotherapy. RESULTS: In 62 patients an objective response rate of 25% was observed. In the first-line setting progression-free survival measured 6.4 months (95% confidence interval [CI]: 4.5-7.3) and overall survival was 10.8 months (95% CI: 7.9-13.7). In the second-line setting progression-free survival was 7.3 months (95% CI: 3.4-11.2) and overall survival was also 7.3 months (95% CI: 4.8-9.8). Psychosocial well-being improved during chemotherapy and the main toxicity observed was neutropenia (40%). CONCLUSIONS: IPM appeared to have a reasonable response rate with an acceptable toxicity profile in the first- and second-line treatment of MPM.

Adult↗
PubMed2007

Oncology and pharmacogenetics in 2007.

Justin Stebbing is a member of the Royal College of Physicians, American Board of Internal Medicine and the Royal College of Pathologists. Originally, Justin trained in medicine at Trinity College Oxford (Oxford, UK), obtaining a triple first class degree. After completion of junior doctor posts in Oxford, he undertook a residency (junior doctor) training at The Johns Hopkins Hospital (MD, USA), before returning to London to continue his training in oncology at The Royal Marsden. Justin then undertook a PhD, funded by the medical research council, investigating the interplay between the immune system and cancer. Specifically, the role of heat shock proteins in tumorigenesis was examined, leading to the development of a cancer vaccine that is currently in clinical trials. Justin has published over 200 papers and book chapters, in journals such as the Lancet, New England Journal, Blood, the Journal of Clinical Oncology and Annals of Internal Medicine, the majority as first or last author. They mainly focus on early and late stage trials of new drugs, mechanisms of disease and prognostic indicators. He is on the editorial board of a number of journals and regularly serves as a referee. Justin's main focus is now in breast cancer, and helping patients with early and late stage disease get better.

Antineoplastic Agents↗
PubMed2006

Highly active antiretroviral therapy and human immunodeficiency virus-associated primary cerebral lymphoma.

From a cohort of 9621 human immunodeficiency virus type 1-infected individuals, we identified 61 patients with primary central nervous system lymphoma (PCL) who had a median survival of 1.3 months. We compared clinicopathologic variables of patients who were treated in the pre-highly active antiretroviral therapy (HAART) and HAART eras and investigated whether exposure to antiretroviral agents with differing cerebrospinal fluid penetrations was associated with risk for PCL. All statistical tests were two-sided. Incidence of PCL was lower in the HAART era (1.2 cases per 1000 patient-years, 95% confidence interval [CI] = 0.8 to 1.9) than in the pre-HAART era (three cases per 1000 years, 95% CI = 2.1 to 4.0; P<.001), and overall survival was longer (median survival = 32 days, range = 5-315 days, versus 48 days, range = 15-1136 days; log rank P = .03). In the HAART era, fewer patients had prior acquired immunodeficiency syndrome-defining illnesses than in the pre-HAART era (64% versus 90%; P = .013), and patients were more likely to have the diagnosis of PCL confirmed histologically or by polymerase chain reaction (77% versus 26%; P<.001). Exposure to specific antiretroviral agents was not associated with risk for PCL.

Acquired Immunodeficiency Syndrome↗
PubMed2006

A prognostic index for AIDS-associated Kaposi's sarcoma in the era of highly active antiretroviral therapy.

BACKGROUND: AIDS-associated Kaposi's sarcoma remains common in individuals with HIV-1 infection in the era of highly active antiretroviral therapy (HAART). We developed a simple model for predicting mortality on the basis of clinical characteristics present at the time of diagnosis of Kaposi's sarcoma. METHODS: Of 5873 individuals with HIV-1 infection, 326 (6%) developed Kaposi's sarcoma; for 262 (80%) this was their first AIDS-defining illness. We did univariate and multivariate Cox regression analyses to identify covariates predictive of overall survival and validated our model with an independent data set of 446 patients with Kaposi's sarcoma. RESULTS: In the primary model, we developed a prognostic score from 0 to 15 starting at 10. Having Kaposi's sarcoma as the AIDS-defining illness (-3 points) and increasing CD4 count (-1 point for every complete 100 cells per mm3) improved prognosis; age of 50 years or older (2 points) and having another AIDS-associated illness at the same time (3 points) conveyed a poorer prognosis. In individuals with prognostic scores of 0, 5, 10, and 15, probability of survival at 1-year was 0.993, 0.967, 0.834, and 0.378, and at 5 years was 0.984, 0.918, 0.631, and 0.084, respectively. Increasing prognostic score by 1 increased 1-year death hazard ratio by 40% (95% CI 28-53%; bootstrapped hazard ratio 1.39, 1.25-1.51). The index had concordance of 76.8% (71.7-82.3). INTERPRETATION: We identified four prognostic factors that can be used to obtain an accurate prognostic index at diagnosis of AIDS-associated Kaposi's sarcoma. This index is widely applicable and can be used to guide therapeutic options.

AIDS-Related Opportunistic Infections↗
PubMed2006

Comparative pharmacogenomics of antiretroviral and cytotoxic treatments.

Few genetic markers are used routinely to predict clinical effectiveness and toxic effects despite the fact that physicians and their patients are consistently confronted with this balance. Because one of the goals of pharmacogenomics is to identify individuals and target populations that might have adverse outcomes, pharmaceutical companies have been reluctant to use a strategy that might identify patients who are not eligible for a particular treatment. This view is changing because drug-discovery programmes and treatments that target specific pathways, are showing improvements in surrogate and survival endpoints. HIV and cancer are now regarded as chronic diseases, which commonly need life-long systemic treatment from the time of diagnosis. HIV and cancer medicine have used pharmacogenomics to some extent in clinical care. Common and classic features of pharmacogenomics that are related to both antiretroviral treatment and to cytotoxic treatment are discussed in this review, providing a framework for individual treatment of these diseases.

Anti-Retroviral Agents↗
PubMed2006

Significance of variation within HIV, EBV, and KSHV subtypes.

Since their initial transmission to humans, viruses have diversified extensively through recombination and mutation. The presence of intra- and inter-individual viral diversity influences disease progression, drug resistance, and therapy and presumably explains the conflicting results in many studies, including the failure of peptide-based vaccination strategies. Although HIV is a small RNA virus, coinfection with large DNA viruses, notably the oncogenic gamma-herpesviridae human herpesvirus-8 and Epstein Barr virus, is common. This coinfection occurs secondary to immunosuppression and shared transmission routes with high-risk predisposing behavior. In addition, all 3 of these viruses can lead to chronic infections, long periods of latency, and reactivation characterized by pain and suffering. The efficient targeting of their genetic diversity represents one of the major challenges in their control, both in prophylactic and therapeutic strategies. An understanding of diversity will help delineate whether population-specific vaccine strategies are necessary.

Animals↗
PubMed2006

Hepatocellular cancer in HIV-infected individuals: tomorrow's problem?

A number of cancers occur with increased frequency in individuals with HIV infection. There is a debate as to whether or not hepatocellular cancer is one of these tumors. This article reviews the current data regarding incidence etiology, treatment and outcome for HIV-related hepatocellular cancer. It also attempts to predict future areas of importance in the management of these patients in the era of highly active antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Non-Hodgkin's lymphoma and the CNS: prophylaxis and therapy in immunocompetent and HIV-positive individuals.

The involvement of the CNS in individuals with non-Hodgkin's lymphoma is a well-recognised complication. Despite the progress that has been made in controlling cancer at most sites in the body, the outcome of individuals affected by meningeal infiltration is dismal and few patients survive for more than a few months. There are few studies that have addressed the management of CNS disease in AIDS-associated non-Hodgkin's lymphoma, and treatment algorithms have been formulated secondary to protocols in immunocompetent individuals. The prevention and treatment of CNS disease is an important aspect of lymphoma management, and new medications, such as a sustained-release formulation of intrathecal cytarabine, will have an increasingly relevant role.

Algorithms↗
PubMed2006

Epigenetics: an emerging technology in the diagnosis and treatment of cancer.

Transcriptional silencing resulting from changes in epigenetic regulation of gene expression is the most frequent mechanism by which tumor suppressor genes are inactivated in human cancer. Genes participating in numerous functional groups and pathways leading to malignancy are subject to aberrant CpG methylation, with associated downregulation of expression, in human carcinogenesis. Methylation profiling can identify distinct subtypes of common human cancers and may have utility in predicting clinical phenotypes in individual patients, including sensitivity to chemotherapeutic agents. Hypomethylating agents have clinical activity in some hematological malignancies, and there is accumulating evidence correlating clinical response with demethylation and concomitant reactivation of expression of specific target genes. Epigenetic analysis is likely to have an increasingly important part to play in the diagnosis, prognostic assessment and treatment of malignant disease.

Animals↗
PubMed2006

The genomics of new drugs in sickle cell disease.

The quality of life of patients with sickle cell disease in developed countries has improved significantly over the past two decades. Currently available measures to prevent the painful crises and the complications of the disease include the use of penicillin prophylaxis, antipneumonococcal vaccine, folate administration, chronic red cell transfusions in patients with cerebrovascular disease, iron chelating agents, fetal hemoglobin-enhancing agents, such as hydroxyurea, decitabine and butyrate, drugs that augment the endogenous nitric oxide levels and agents that restore red cell dehydration. Sickle cell patients show a broad phenotypic expression and a great variability in treatment response. Genetic association studies, which attempt to link polymorphisms with certain disease phenotypes and drug response, are taking the first steps in aiding individualized therapy in sickle cell patients in order to enhance efficacy and reduce toxicity.

Anemia, Sickle Cell↗