Angelo J. Cambio

The AKT inhibitor perifosine in biochemically recurrent prostate cancer: a phase II California/Pittsburgh cancer consortium trial.

BACKGROUND Perifosine is an oral alkylphospholipid that inhibits cancer cell growth through decreased Akt phosphorylation. We conducted a phase II trial of perifosine in patients with biochemically recurrent, hormone-sensitive prostate cancer. PATIENTS AND METHODS Eligible patients had histologically confirmed prostate cancer, previous prostatectomy and/or radiation therapy, and rising prostate-specific antigen (PSA) without radiographic evidence of metastasis. Previous androgen deprivation therapy < 9 months in duration (completed >or= 1 year before registration) was allowed. The primary endpoint was PSA response, defined as a decrease by >or= 50% from the pretreatment value. Treatment was composed of a loading dose of perifosine 900 mg orally on day 1, then 100 mg daily starting 24 hours later. RESULTS Of 25 patients, 24 were evaluable for response. After a median follow-up of 8 months, 5 patients (20%) had a reduction in serum PSA levels, but none met criteria for PSA response. Three patients immediately progressed with no response to therapy. Median progression-free survival was 6.64 months (range, 4.53-12.81 months). No change in the PSA doubling time (7 months) was observed before and after treatment initiation. Dose-limiting toxicities (all grade 3) included hyponatremia, arthritis, hyperuricemia, and photophobia. CONCLUSION Although well tolerated, perifosine did not meet prespecified PSA criteria for response as a single agent in biochemically recurrent prostate cancer. However, 20% of patients had evidence of PSA reduction, suggesting modest single-agent clinical activity. The role of perifosine in combination with androgen deprivation or chemotherapy is currently under investigation.

Clinical implications of neuroendocrine differentiation in prostate cancer.

The cellular signaling pathways of the prostate play a central role in the induction, maintenance, and progression of prostate cancer (CaP). Neuroendocrine (NE) cells demonstrate attributes that suggest they are an integral part of these signaling cascades. We summarize what is known regarding NE cells in CaP focusing on NE cellular transdifferentiation. This significant event in CaP progression appears to be accelerated by androgen deprivation (AD) treatment. We examine biochemical pathways that may impact NE differentiation in a chronological manner focusing on AD therapy (ADT) as a central event in inducing androgen-independent CaP. Our analysis is limited to the common adenocarcinoma pattern of CaP and excludes small-cell and carcinoid prostatic variants. In conclusion, we speculate on the future of treatment and research in this area.

Development and Validation of the Fecal Incontinence and Constipation Quality of Life Measure in Children With Spina Bifida

PURPOSE Fecal incontinence and constipation in children with spina bifida are recognized to impact quality of life. Most disease specific quality of life instruments on fecal incontinence target adults and/or children without neuropathic bowel. We developed an instrument to evaluate bowel function and its impact on quality of life in children with spina bifida and their caregivers. MATERIALS AND METHODS A 51-item questionnaire termed the FIC QOL (Fecal Incontinence and Constipation Quality of Life) survey was developed from expert opinion, patient interviews, and modification of previously published adult and pediatric studies for nonneuropathic bowel dysfunction. The items are divided into 7 quality of life factor groupings, including bowel program, dietary management, symptoms, travel and socialization, family relationships, caregiver emotional impact and financial impact. The questionnaire was given to caregivers of children with and without spina bifida. Discriminant validity was evaluated by comparing the spina bifida and control groups. Test-retest reliability was evaluated by having 41 patients complete 2 surveys within 4 to 6 weeks. RESULTS Comparing questionnaires from 92 index patients and 52 controls showed a statistically significant difference for all 7 quality of life factor groupings. The FIC QOL instrument objectively demonstrated the negative impact of fecal incontinence and constipation on quality of life in these families. Comparing 82 questionnaires at 2 time points demonstrated the reliability of all FIC QOL questions. CONCLUSIONS The FIC QOL instrument provides a valid and reliable measure of the effect of fecal incontinence and constipation on the quality of life of caregivers and their children with spina bifida.

Non-surgical management of multicystic dysplastic kidney.

To better define the outcome and association of multicystic dysplastic kidney (MCDK) with hypertension, vesico‐ureteric reflux (VUR), infection and cancer, as there is no consensus on the management of patients born with MCDK. The risk of cancer has dictated the surgical management of the disease in the past.

Management approaches to small renal tumours

Currently NSS is an established approach for patients with localized RCC whether or not there is a clinical indication to preserve renal function. OPN is the ‘gold standard’ for NSS; the wave of new minimally invasive technologies and techniques are compared to the standard created by OPN. The standard accepted indication for elective NSS is a single, localized RCC of < 4 cm in diameter on imaging [4]. OPN offers efficacy, morbidity and mortality on a par with radical nephrectomy. The long-term cancer-specific survival of OPN is comparable with that of radical nephrectomy. In a review of nine studies, Novick [4] reported results of open NSS for RCC in 1262 patients; the mean cancer-specific survival for all patients undergoing OPN for localized RCC was 88– 97.5%, with a mean follow-up of 5–6 years.

Recent developments in advanced urothelial cancer

Purpose of review Metastatic or unresectable urothelial cancer of the urinary bladder has traditionally been treated with systemic chemotherapy, which is most often platinum-based. The long-term survival data and the associated toxicities from this form of therapy have spurred continuing interest in finding novel treatment options for this malignancy. Recent findings Recently, trials of new chemotherapy combinations, many incorporating platinum analogs or deleting platinum entirely, have been reported. None has yet been shown to be superior to cisplatin-based regimens. In addition, recent advances in imaging and laboratory technologies have provided new avenues to understand urothelial cancer behavior and prognosis. These advances provide optimism for improvements in the diagnosis, staging, and ultimately, selection of therapy for patients with urothelial cancer. Summary This review will summarize recent developments (circa 2004) in the diagnosis and management of advanced bladder cancer.

Is the use of anything but MVAC justified in the evidence-based medicine era?

For the physician, external evidence is commonly in the form of published literature, for which there are various types: systematic reviews and meta-analyses of randomized controlled trials (RCTs), non-randomized controlled trials, case reports, clinical examples and consensus meetings [4]. The type of trial contributes to the quality of data. Generally, RCTs provide the most reliable data by limiting potential biases and confounding factors. Combining the data from multiple RCTs, as is done in meta-analyses, can potentially yield greater statistical power to find differences in outcomes between therapeutic choices. The evidence in the published literature can be ranked or assigned a level of importance using a system of criteria such as that described by the American Society of Clinical Oncology (Table 1) [5]. The type of evidence determines the reliability of the data, but all types of evidence can play a role in patient management. For example, case studies of individual patients may be the only source of evidence for rare conditions. The physician practising EBM would appraise a case study and decide whether or not the information affects the management of a particular patient. Advanced bladder cancer is one tumor type in which EBM principles can be applied to determine the best treatment option.