Showing papers by "Thomas Powles published in 2007"
TL;DR: The efficacy and safety of rituximab as initial monotherapy and correlate clinical findings with immune subset, plasma cytokine, and HIV and KSHV virologic variables are investigated.
Abstract: Background: HIV-associated multicentric Castleman disease is a rare lymphoproliferative disorder with marked systemic symptoms attributed to cytokine disarray. Many therapeutic approaches in small series of patients have proved largely unsuccessful to date.
Objective: To investigate the efficacy and clinicopathologic variables associated with first-line treatment for HIV-associated multicentric Castleman disease with the anti-CD20 monoclonal antibody rituximab.
Design: Single-group, open-label, phase II trial.
Setting: 3 teaching hospitals in England.
Patients: Previously untreated patients with histologically proven HIV-associated multicentric Castleman disease.
Intervention: 4 infusions of rituximab, 375 mg per m2 of body surface area, at weekly intervals.
Measurements: Response was evaluated clinically and radiologically and by measuring plasma Kaposi sarcoma–associated herpesvirus viral load.
Results: 21 consecutive patients (18 men) with plasmablastic multicentric Castleman disease were recruited. The median follow-up was 12 months (range, 1 to 49 months). One patient died before completing therapy, 20 achieved remission of symptoms, and 14 (67%) achieved a radiologic response. The overall and disease-free survival rates at 2 years were 95% (95% CI, 86% to 100%) and 79% (CI, 49% to 100%), respectively. Plasma acute-phase proteins, immunoglobulins, and Kaposi sarcoma–associated herpesvirus viral load decreased after rituximab therapy. The main adverse effect was reactivation of Kaposi sarcoma.
Limitation: The study had no comparison group.
Conclusion: Rituximab may be clinically valuable as initial therapy for HIV-associated multicentric Castleman disease.
163 citations
TL;DR: There is consistent evidence that FDG-PET provides important diagnostic information in detecting metastatic and recurrent germ cell tumours and it might offer additional information in the staging and restaging of bladder and renal cancer.
142 citations
TL;DR: The outcome of patients with relapsed GTN is good, however, patients with primary chemo-refractory disease do poorly and novel therapies are required for this group of patients.
Abstract: The majority of women requiring chemotherapy for gestational trophoblastic disease (GTN) are cured with their initial chemotherapy treatment. However, a small percentage either become refractory to treatment, or relapse after the completion of treatment. This study investigates the characteristics and outcome of these patients. Patients were identified from the Charing Cross Hospital GTD database. The outcome of these patients with relapsed disease was compared to those with refractory disease. Between 1980 and 2004, 1708 patients were treated with chemotherapy for GTN. Sixty (3.5%) patents relapsed following completion of initial therapy. The overall 5-year survival for patients with relapsed GTN was 93% (95% CI 86-100%). The overall survival for patients with low-risk and high-risk disease at presentation, who subsequently relapsed was 100% (n=35), and 84% (n=25) (95% CI: 66-96%: P<0.05), respectively. Eleven patients were identified who failed to enter remission and had refractory disease. These patients had a worse outcome compared to patients with relapsed disease (5-year survival 43% (95% CI:12-73% P<0.01)). The outcome of patients with relapsed GTN is good. However, patients with primary chemo-refractory disease do poorly and novel therapies are required for this group of patients.
93 citations
TL;DR: Rituximab is active as initial treatment for HIV-associated multicentric Castleman disease (HMCD) and its efficacy and safety in ritUXimab pretreated, relapsed patients has not been previously described.
37 citations
TL;DR: Topoisomerase I-based IPO chemotherapy that lacks etoposide is very active in multiply relapsed GCT, and this data merit further investigation.
26 citations
TL;DR: GAMEC is a novel intensive regimen for this group of patients producing encouraging responses, although with significant toxicity, for those in whom it fails, further therapy is still possible with durable responses being seen.
Abstract: There is no consensus as to the management of untreated poor prognosis or relapsed/refractory germ cell tumours. We have studied an intensive cisplatin-based regimen that incorporates high-dose methotrexate (HD MTX) and actinomycin-D and etoposide every 14 days (GAMEC). Sixty-two patients were enrolled in a phase 2 study including 27 who were untreated (IGCCCG, poor prognosis) and 35 with progression despite conventional platinum based chemotherapy. The pharmacokinetics of the drugs were correlated with standard outcome measures. Twenty of the untreated patients were progression free following GAMEC and appropriate surgery, as were 18 individuals in the pretreated group. None of the established prognostic factors for therapy for pretreated patients could identify a poor-prognosis group. Five out of nine late relapses to prior chemotherapy were progression free following GAMEC and appropriate surgery. All patients had at least one episode of febrile neutropenia and there were five (8%) treatment-related deaths. PK values were not predictive of efficacy or toxicity, although the dose intensity in the pretreated group of patients, especially of HD MTX, was significantly correlated with progression-free survival (PFS). GAMEC is a novel intensive regimen for this group of patients producing encouraging responses, although with significant toxicity. For those in whom it fails, further therapy is still possible with durable responses being seen.
24 citations
TL;DR: It is indicated that neoadjuvant therapy followed by prostatectomy may improve long‐term outcomes for patients with high‐risk localized disease and this approach provides a paradigm for evaluating the activity and mechanism of action of new agents as correlative studies are facilitated by the availability of tumor tissue before and after therapy.
Abstract: The results of this assessment of the literature indicated that neoadjuvant therapy followed by prostatectomy may improve long-term outcomes for patients with high-risk localized disease. In addition, this approach provides a paradigm for evaluating the activity and mechanism of action of new agents as correlative studies are facilitated by the availability of tumor tissue before and after therapy. The authors determined that a multidisciplinary approach involving oncologists, urologists, and pathologists is critical to the success of this model. Recent and ongoing studies of neoadjuvant therapy followed by prostatectomy were reviewed.
20 citations
13 citations
TL;DR: It is suggested that oxaliplatin is a potent agent in bladder cancer cell lines and is superior to carboplatin in this in vitro setting, which justifies the clinical studies using this drug that are underway.
Abstract: Background: Oxaliplatin is a 3rd generation platinum analogue, which is active in a broad spectrum of tumours. Clinical trials using this drug in bladder cancer are underway, but no
12 citations
TL;DR: The CD8 count appears to provide independent prognostic information in individuals with AIDS-associated Kaposi's sarcoma and is clinically useful in patients with KS, suggesting its effect on the overall prognostic index is small.
Abstract: Purpose A prognostic index for AIDS-associated Kaposi's sarcoma (KS) diagnosed in the era of highly active antiretroviral therapy (HAART) was based on routine clinical and laboratory characteristics. Because immune subset measurement is often performed in HIV-positive individuals, we examined whether these were predictive of mortality independently of the prognostic index, or could predict time to progression of KS. Patients and Methods We performed univariate and multivariate Cox regression analyses on a data set of 326 individuals with AIDS-associated KS to identify immune subset covariates predictive of overall survival and time to progression. Adaptive (CD8 T cell and CD19 B cell) and innate (CD16/56 natural-killer cell) immune parameters were studied by flow cytometry. Results In univariate analyses, all three immune subsets had significant effects on overall survival (P < .025). In multivariate analyses including the prognostic index, only CD8 counts remained significant (P = .026), although its eff...
9 citations
TL;DR: It is found that ritonavir-boosted atazanavir is not associated with the development of primary genotypic resistance in individuals failing this combination, without previous protease inhibitor failure.
Abstract: Few data exist regarding the resistance profile in individuals receiving atazanavir. We found that ritonavir-boosted atazanavir is not associated with the development of primary genotypic resistance in individuals failing this combination, without previous protease inhibitor failure. It is rarely associated with the acquisition of primary mutations in individuals with previous protease inhibitor exposure. This is particularly important because of the increasing use of atazanavir monotherapy, and implies that treatment failure is caused by lack of potency.
Journal Article•
TL;DR: In this paper, the authors investigated the utility of brain CT in determining the outcome of leptomeningeal disease, despite MR imaging being the gold standard, and they found that CT brain scan appears not to offer additional prognostic information following a lumbar puncture in patients with AIDS-related systemic non-Hodgkin lymphoma.
Abstract: BACKGROUND AND PURPOSE: AIDS-related systemic non-Hodgkin lymphoma (ARL) remains a significant cause of morbidity and mortality in patients infected with the human immunodeficiency virus (HIV-1), and leptomeningeal disease in this setting has a dismal prognosis. We investigated the utility of brain CT in determining the outcome of leptomeningeal disease, despite MR imaging being the gold standard. MATERIALS AND METHODS: From a cohort of 9621 HIV-1-seropositive individuals, we identified those diagnosed with ARL in the highly active antiretroviral therapy (HAART) era who had both a lumbar puncture and central nervous system imaging using a CT brain scan at the time of initial diagnosis, and we compared survival parameters between those with and without leptomeningeal disease. RESULTS: In a cohort of 82 individuals with ARL treated in the era of HAART, we found that the survival of individuals with leptomeningeal disease defined as the presence of cells in the CSF was worse compared with that of other patients ( P = .0026). However, when defined by the presence of abnormal enhancement or parenchymal lesions on a CT scan, the outcome was not significantly different. CONCLUSION: A CT brain scan appears not to offer additional prognostic information following a lumbar puncture in patients with ARL.
Journal Article•
TL;DR: This abstract summarises late events in these 3 cohorts of patients treated with radiotherapy for second cancer and Carboplatin with difficulties in detecting recurrence on surveillance out to 10 years.
Abstract: 5089 Background: Radiotherapy is associated with an increase of second cancer and cardiovascular disease. Because of difficulties in detecting recurrence on surveillance which can occur out to 10 y...
TL;DR: HIV associated multicentric Castlemans is a rare lympohproliferative disorder and most treatment options to date have proved largely unsuccessful, but this study investigated the possibility of using chemotherapy to treat MCD.
Abstract: 8049 Background: HIV associated multicentric Castlemans (MCD) is rare lympohproliferative disorder and most treatment options to date, have proved largely unsuccessful. This study investigated the ...
TL;DR: A prognostic index for Acquired Immunodeficiency Syndrome (AIDS)-associated Kaposi sarcoma (KS) diagnosed in the era of highly active antiretroviral therapy (HAART) based on clinical and routine laboratory characteristics and found all 3 immune subsets had significant effects on overall survival.
Abstract: 20500 Background: We recently published a prognostic index for Acquired Immunodeficiency Syndrome (AIDS)-associated Kaposi sarcoma (KS) diagnosed in the era of highly active antiretroviral therapy ...
Journal Article•
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01 Jan 2007
TL;DR: A CT brain scan appears not to offer additional prognostic information following a lumbar puncture in patients with ARL, and when defined by the presence of abnormal enhancement or parenchymal lesions on a CT scan, the outcome was not significantly different.
Abstract: BACKGROUND AND PURPOSE: AIDS-related systemic non-Hodgkin lymphoma (ARL) remains a significant cause of morbidity and mortality in patients infected with the human immunodeficiency virus (HIV-1), and leptomeningeal disease in this setting has a dismal prognosis. We investigated the utility of brain CT in determining the outcome of leptomeningeal disease, despite MR imaging being the gold standard. MATERIALS AND METHODS: From a cohort of 9621 HIV-1-seropositive individuals, we identified those diagnosed with ARL in the highly active antiretroviral therapy (HAART) era who had both a lumbar puncture and central nervous system imaging using a CT brain scan at the time of initial diagnosis, and we compared survival parameters between those with and without leptomeningeal disease. RESULTS: In a cohort of 82 individuals with ARL treated in the era of HAART, we found that the survival of individuals with leptomeningeal disease defined as the presence of cells in the CSF was worse compared with that of other patients (P .0026). However, when defined by the presence of abnormal enhancement or parenchymal lesions on a CT scan, the outcome was not significantly different. CONCLUSION: A CT brain scan appears not to offer additional prognostic information following a lumbar puncture in patients with ARL.