Gastrointestinal and genitourinary toxicity profiles of metformin versus placebo in men with prostate cancer receiving prostate radiotherapy: interim toxicity results of a double-blinded, multicenter, phase II randomized controlled trial.

Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18-36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.

Management of Hormone Deprivation Symptoms After Cancer.

Cancer survivors often experience symptoms related to hormone deprivation, including vasomotor symptoms, genitourinary symptoms, and sexual health concerns. These symptoms can occur due to natural menopause in midlife women, or they can be brought on by oncologic therapies in younger women or men. We searched PubMed for English-language studies from January 1990 through January 2016 to identify relevant articles on the management of hormone deprivation symptoms, including vasomotor, genitourinary, and sexual symptoms in patients with cancer. The search terms used included hormone deprivation, vasomotor symptoms, hot flash, vaginal dryness, sexual dysfunction, and breast cancer. This manuscript provides a comprehensive description of data supporting the treatment of symptoms associated with hormone deprivation.

Spectrum of medication-induced complications in the abdomen: role of cross-sectional imaging.

OBJECTIVE: This article provides a comprehensive review of the role of MDCT and MRI in the diagnosis of drug-induced complications in the abdomen and pelvis in adults. A systematic organ-based review of these complications is presented, including but not limited to hepatic changes after chemotherapy, renal complications such as tumor lysis syndrome and lithium nephropathy, gastrointestinal manifestations, various opportunistic infections and secondary neoplasms, mycotic aortic aneurysm from intravesical bacille Calmette-Guérin, complications of anticoagulant therapy, and oral contraceptives. CONCLUSION: Advancements in imaging have led to recognition of radiologic features of previously unsuspected diseases. Occasionally, imaging may also identify effects of treatments instituted for these diseases. Consequently, imaging plays a critical role in the accurate diagnosis of a broad spectrum of drug-induced complications in the abdomen, both in emergent and nonemergent settings. Knowledge of the natural history, clinical manifestations, and salient imaging features of these entities is crucial to facilitate accurate clinical diagnosis in a timely fashion.

[Combined external radiotherapy and hormone therapy in patients with locally advanced prostate cancer: predictive factors of genitourinary toxicity]. / Tratamiento combinado con radioterapia externa y hormonoterapia en los pacientes con cáncer de próstata localmente avanzado: factores predictivos de toxicidad genitourinaria.

INTRODUCTION: Radiotherapy and androgen deprivation are an established treatment option for locally advanced prostate cancer. We evaluate outcomes in efficacy and toxicity for patients treated with this combined therapy at our institution. METHODS: A retrospective study of 80 patients with locally advanced prostate cancer treated with radiotherapy combined with neo-adjuvant (2 months) and adjuvant (24 months) androgen deprivation. We studied the clinical variables and side effects. We evaluated treatment outcomes using PSA nadir and biochemical failure, and recorded acute and late gastrointestinal and urinary toxicity. We assessed the correlation between clinical variables and urinary toxicity by means of univariate and multivariate analyses (multiple logistic regression). RESULTS: The mean patient age was 68 ± 5.81 years; the initial PSA was 20.05 ± 16.27 ng/ ml and the mean prostate volume 43.7 ± 27.57 cc. The clinical stage was T3a in 33% and T3b in 66%. The Gleason score was <7 in 39%, 7 in 46% and ≥8 in 15%. The mean follow-up was 44.4 months and biochemical failure was observed in 3 cases. Acute urinary toxicity was recorded in 90% of the patients (chronic in 35%) and acute gastrointestinal toxicity in 75% (late in 32%). In a univariate analysis, prostate volume and urinary symptoms were statistically correlated to acute and late urinary toxicity. Both prostate volume and urinary symptoms were independently associated with an increase in urinary toxicity in the logistic regression analysis. CONCLUSIONS: Hormone-radiotherapy is a valid option to locally treat advanced prostate cancer with optimal short-term outcomes, although it is not devoid of side effects. Prostate volume and urinary symptoms before treatment can predict genitourinary toxicity.

CT findings of chemotherapy-induced toxicity: what radiologists need to know about the clinical and radiologic manifestations of chemotherapy toxicity.

Cancer chemotherapy has evolved from cytotoxic agents and now includes several new agents that target specific molecules responsible for the regulation of cell growth, nutrient supply, and differentiation. These molecularly targeted therapies have a different mechanism of action than do classic cytotoxic agents, which predominantly attack rapidly proliferating cells. Not surprisingly, therefore, the toxicity of targeted and cytotoxic agents may differ in both clinical and radiologic presentation. Many of the toxicities of targeted therapies are not cumulative or dose dependent, some are asymptomatic, and others may first manifest radiologically. It is imperative that radiologists be aware of these toxicities and that they learn to recognize the relevant findings so that they can provide a complete differential diagnosis and thus play an important role in patient care.

Urogenital history in veterans exposed to high-dose sulfur mustard: a preliminary study of self-reported data.

INTRODUCTION: To date, little information exists regarding urogenital diseases in those who have been exposed to sulfur mustard (SM). We report the self-reported history of urologic conditions and findings on physical examination in a group of male veterans 19 to 26 years after exposed to high-dose sulfur mustard. MATERIALS AND METHODS: Data on urologic health conditions of a nationwide health survey were used in this study. This survey included all 289 Iranian male veterans who had been exposed to high doses of SM between 1983 and 1989. Demographic data, exposure-related data, health status, and also self-reported lifetime history of urologic conditions were analyzed. History of benign prostatic hyperplasia, recurrent urinary tract infections, pyelonephritis, urinary calculi, kidney failure, and urogenital neoplasms were specifically concerned. RESULTS: The mean age of the veterans was 45.0 ? 7.5 years (range, 30 to 75 years). An interval of 19 to 26 years had passed from exposure to SM. Fifty veterans (17.3%) had a positive history of urinary calculi, 25 (8.7%) had recurrent urinary tract infections, 5 (1.7%) had BPH, and 2 (0.7%) had kidney failure. None of them had experienced urogenital malignancies. Neither recurrent urinary tract infections nor urinary calculi were significantly associated with age, medications and their doses, or SM-induced late complications in other organs. CONCLUSION: This study adds the prevalence of self-reported urologic conditions to our limited knowledge on SM-exposed veterans' health condition, without finding any link neither to demographic, nor to the severity of health complications related to the SM exposure.

High dose zinc increases hospital admissions due to genitourinary complications.

PURPOSE: Zinc is a common dietary supplement that is widely believed to have beneficial health effects. To assess the impact of high dose supplemental zinc on genitourinary diseases we analyzed a recent randomized trial comparing zinc, antioxidants and their combination to placebo for complications related to the genitourinary tract. MATERIALS AND METHODS: In a further analysis of the recent Age-related Eye Disease Study we examined the data pool for primary International Classification of Diseases, 9th revision codes given for hospital admissions related to urological problems. The Age-Related Eye Disease Study randomized 3,640 patients with age related macular degeneration to 1 of 4 study arms, including placebo, antioxidants (500 mg vitamin C, 400 IU vitamin E and 15 mg beta-carotene), 80 mg zinc and antioxidant plus zinc. Statistical analyses using Fisher's exact test were performed. RESULTS: We found a significant increase in hospital admissions due to genitourinary causes in patients on zinc vs nonzinc formulations (11.1% vs 7.6%, p = 0.0003). The risk was greatest in male patients (RR 1.26, 95% CI 1.07-1.50, p = 0.008). In the study group of 343 patients requiring hospital admission the most common primary International Classification of Diseases, 9th revision codes included benign prostatic hyperplasia/urinary retention (benign prostatic hyperplasia), urinary tract infection, urinary lithiasis and renal failure. When comparing zinc to placebo, significant increases in urinary tract infections were found (p = 0.004), especially in females (2.3% vs 0.4%, RR 5.77, 95% CI 1.30-25.66, p = 0.013). Admissions for urinary lithiasis approached significance in men on zinc compared to placebo (2.0% vs 0.5%, RR = 4.08, 95% CI 0.87-19.10). There was no increase in prostate or other cancers with zinc supplementation. A significant decrease in prostate cancer diagnoses was seen in patients receiving antioxidants vs placebo (RR = 0.6, 95% CI 0.49-0.86, p = 0.049). Subgroup analysis revealed that this finding was significant in men who smoked but not in nonsmokers. CONCLUSIONS: Zinc supplementation at high levels results in increased hospitalizations for urinary complications compared to placebo. These data support the hypothesis that high dose zinc supplementation has a negative effect on select aspects of urinary physiology.

Results of a phase II study using estramustine phosphate and vinblastine in combination with high-dose three-dimensional conformal radiotherapy for patients with locally advanced prostate cancer.

PURPOSE: To assess the feasibility and tolerance of neoadjuvant and concomitant estramustine phosphate and vinblastine (EV) with high-dose three-dimensional conformal radiotherapy (3D-CRT) for patients with unfavorable-risk prostate cancer. PATIENTS AND METHODS: Twenty-seven patients with unfavorable-risk prostate cancer were enrolled onto a prospective study to determine the feasibility of combining EV with 3D-CRT. Patients were eligible if any of the following requirements were satisfied: (1) Gleason score > or =8 and prostate-specific antigen (PSA) > 10 ng/mL; (2) Gleason score of 7 and PSA > 20 ng/mL; (3) clinical stage T3N0M0 disease with PSA > 20 ng/mL; (4) any patient with T4N0M0 disease; or (5) patients with TXN1MO disease. Therapy consisted of three 8-week cycles of EV and 8 weeks of 3D-CRT. Estramustine phosphate was given orally beginning on week 1 and continued until the completion of 3D-CRT. Each 8-week cycle of vinblastine consisted of 6 weekly intravenous injections followed by a 2-week rest period. Radiation therapy was administered using a three-dimensional conformal approach to a prescription dose of 75.6 Gy. The median follow-up was 26 months (range, 6 to 40 months). RESULTS: Twenty-three (85%) of 27 patients completed the entire course of therapy and were assessable for toxicities and biochemical outcome. Two patients (7%) developed grade 3 hematologic toxicity that resolved, and two patients (7%) developed grade 3 hepatoxicity, manifesting as persistent elevation of serum transaminase levels, necessitating discontinuation of the chemotherapy and withdrawal from the treatment program. The most prominent adverse effects from this regimen were mild to moderate (grade 1 to 2) nausea and fatigue related to estramustine. Mild peripheral edema was seen in 15% of patients and was treated with diuresis. 3D-CRT was tolerated well in these patients. Medications were required for relief of acute grade 2 rectal (gastrointestinal [GI]) and urinary (genitourinary [GU]) symptoms in 35% and 48% of patients, respectively. Three patients developed acute grade 3 GU toxicities. The 2-year actuarial likelihood of late grade 2 GI toxicity was 20%. No late grade 3 or 4 GI toxicities were observed. The 2-year actuarial likelihoods of late grade 2 and 3 GU toxicities were 25% and 12%, respectively. No grade 4 GU toxicity was observed. CONCLUSION: Neoadjuvant and concomitant EV with high-dose 3D-CRT is well tolerated in patients with unfavorable-risk prostate cancer. Although the incidence of modest (grade 2) late GI and GU toxicities seem to be increased compared with 3D-CRT alone or in combination with androgen ablation therapy, no severe toxicities were encountered with this regimen.

[Acute myelitis after vaccination against hepatitis B]. / Myélite aiguë après vaccination contre l'hépatite B.

A 56-year old man was hospitalized for spasmodic paraparesis with sphincter disorders. After exclusion of spinal cord compression and all other inflammatory, infectious or neoplastic causes, the possibility of a connexion with an hepatitis B vaccination performed with a recumbent vaccine three weeks before the neurological disorders appeared was considered. The pathogenesis of such a myelitis remains uncertain. It is based on the possible reactivation of a dormant virus or a crossed antigenic reaction between a protein of the vaccine and the nervous system. The course of the disease is usually favourable. The frequency of this complication would be more accurately determined if all neurological manifestations occurring after hepatitis B vaccination were reported.