Treatment patterns and trends in patients dying of prostate cancer in Quebec: a population-based study.

INTRODUCTION: Since just after the year 2000 in Quebec, the management of metastatic castration-resistant prostate cancer (mcrpc) has evolved considerably, with the inclusion of docetaxel-based chemotherapy, bone-targeted therapies (zoledronic acid and denosumab), and more recently, abiraterone, enzalutamide, and cabazitaxel for docetaxel-refractory patients. In the present study, we aimed to analyze contemporary mcrpc management patterns and therapy utilization trends in Quebec. METHODS: The study cohort consisted of patients dying of prostate cancer (pca) between January 2001 and December 2013, selected from Quebec public health care insurance databases. Patient selection was based on death from a pca-related cause or therapy used according to the Canadian Urological Association guidelines on mcrpc management. Treatments included chemotherapy (mitoxantrone before 2005 and docetaxel after 2005), abiraterone, bone-targeted therapy (zoledronic acid or denosumab, or both), and palliative radiation therapy (rt). During the study period, neither enzalutamide nor cabazitaxel was publicly reimbursed in Quebec, and as a result, no capture of their use was possible for this study. Multivariate logistic regression was used to identify factors associated with the probability of receiving chemotherapy, bone-targeted therapies, and palliative rt before death from pca. RESULTS: Overall, the database search identified 3106 patients who died of pca between January 2001 and December 2013. Median age of death was 78 years. Of those 3106 patients, just 2568 (83%) received mcrpc-specific treatments: chemotherapy, abiraterone, palliative rt, or bone-targeted therapy; the other 17% of the patients were managed solely with maximum androgen blockade (androgen deprivation therapy plus anti-androgens) despite a record of pca-related death. Logistic regression analyses indicate that patients dying after 2005 were more likely to have received chemotherapy [odds ratio (or): 1.51; 95% ci: 1.22 to 1.85] and bone-targeted therapy (or: 1.97; 95% ci: 1.64 to 2.37). Age was a significant predictor for the use of chemotherapy, bone-targeted therapy, and palliative rt (ors in the range 0.96-0.98, p < 0.05). CONCLUSIONS: Patient age seems to be a strong determinant in the of selection mcrpc therapy, affecting the probability of the use of chemotherapy, bone-targeted therapy, or palliative rt. Although chemotherapy is still used only in a small percentage of patients, the introduction of new therapies-such as bone-targeted therapy, docetaxel, and abiraterone-affected treatment selection over time. The availability of enzalutamide since February 2014 will likely produce additional changes in mcrpc management.

Management of Dysphagia in Esophageal Adenocarcinoma Patients Undergoing Neoadjuvant Chemotherapy: Can Invasive Tube Feeding be Avoided?

BACKGROUND: Neoadjuvant chemotherapy is an accepted standard for locally advanced esophagogastric junction adenocarcinoma. However, the dysphagia frequently associated with this condition may interfere with patient tolerance of this treatment. In many centers, invasive tube feeding, placed either endoscopically, radiographically, or surgically, is used to address this issue, but it can cause significant morbidity. We sought to determine if an approach of goal-directed dietary counseling and appropriately timed neoadjuvant chemotherapy could obviate the need for invasive tube feeding. METHODS: Patients with locally advanced (cT3 or N+) esophageal and esophagogastric junction adenocarcinoma undergoing neoadjuvant TCF [Taxotere, cisplatin 5-fluorouracil (5-FU)], ECF (epirubicin, cisplatin, 5-FU), or FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU) at the McGill University Health Center from March 2007 to September 2012 were identified from a prospective database. All received individualized goal-directed dietary counseling, were monitored for signs/symptoms of malnutrition with serial (baseline/presurgery) body mass index, albumin, and completed serial symptom scores (dysphagia), and quality-of-life questionnaires (Functional Assessment in Cancer Therapy with the esophageal subset, FACT-E). We assessed the response of dysphagia and nutritional status to neoadjuvant chemotherapy and the need for invasive tube feeding. RESULTS: Of 130 patients undergoing neoadjuvant chemotherapy, 78 had severe dysphagia (defined as dysphagia score ≥2 on a 5-point Likert scale), most of whom received TCF (91 %). Overall dysphagia scores improved in 75 (96 %) of 78 patients from a dysphagia score of 3-0, most of which improved after the first cycle of therapy. This was associated with an increase in quality of life (FACT-E scores 117 ± 23 to 140 ± 20). With maintenance of weight (70 ± 22 to 69 ± 24 kg), body mass index (24.5 ± 8 to 23.9 ± 7 kg/m(2)), and serum albumin (40 ± 5 to 37 ± 4 g/L). Only one patient required a stent, and none required jejunostomy or gastrostomy. CONCLUSIONS: Appropriately timed neoadjuvant chemotherapy with a highly effective regimen rapidly restores normal swallowing, maintains nutritional status, and obviates the need for invasive tube feeding in patients with significant dysphagia from esophageal adenocarcinoma.

Cancer-associated hypercalcaemia in squamous-cell malignancies: a survival and prognostic factor analysis.

The aim of this study is to analyse survival and prognostic factors in patients diagnosed with squamous cell carcinoma (SCC) presenting a first episode of cancer-associated hypercalcaemia (CAH). Retrospectively, the authors reviewed data from 220 patients with biopsy proven SCC who presented a first episode of CAH. They were treated in a single centre between 1995 and 2007. The survival analyses were done using the Kaplan-Meier method and Cox analysis. The primary endpoint was the overall survival from the date of hypercalcaemia episode. Median age was 55 years. Median survival was 64 days (1-197). Three independent prognostic factors were identified: brain metastasis (hazard ratio (HR)=2.58 CI (1.03-6.45)), corrected calcaemia>3 mmol/l (HR=1.45 CI (1.05-2.01)) and hypoalbuminaemia (HR=1.48 CI (1.07-2.04)). Using these factors, the authors performed a bedside prognostic score. In conclusion, median survival in patients diagnosed with SCC and CAH is extremely poor. The bedside prognostic score that the authors developed can help to anticipate patients' prognosis and adapt the treatment. This score needs to be validated on an independent cohort.

[Treatment of adult patients with metastatic sarcoma: current shift in concepts]. / Traitement des sarcomes des tissus mous de l'adulte métastatiques: évolution actuelle des concepts.

We describe herein the current concepts tested in clinical trials dedicated to patients with metastatic soft tissue sarcomas: identify predictive factors under anthracyclin-based regimens, identify patients beneficing from polychemotherapy, benefit of maintenance treatment, use of non-progression rate rather than response rate for selecting new drugs, histology-tailored or biological target-tailored second-line treatment.

Megestrol acetate versus metronomic cyclophosphamide in patients having exhausted all effective therapies under standard care.

BACKGROUND: To evaluate the antitumour activity and safety of metronomic cyclophosphamide vs megestrol acetate in progressive and advanced cancer patients having exhausted all effective therapies under standard care. METHODS: Patients were randomly assigned to receive orally metronomic cyclophosphamide (50 mg b.i.d) or megestrol acetate (160 mg only daily) until intolerance or progression (RECIST 1.0). The primary efficacy end point was a 2-month progression-free rate (PFR(2m)). According to Optimal Simon's design and the following assumptions, namely, P0=5%, P1=20%, alpha=beta=10%, the treatment is considered as effective if atleast 5 out of 44 patients achieved PFR(2m). RESULTS: Between September 2006 and January 2009, 88 patients were enrolled. Two patients experienced grade 3-4 toxicities in each arm (4%). One toxic death occurred in the megestrol acetate arm as a consequence of thrombosis. The metronomic cyclophosphamide arm reached the predefined level of efficacy with a PFR(2m) rate of 9 out of 44 and a PFR(4m) rate of 5 out of 44. The MA arm failed to achieve the level of efficacy with a PFR(2m) of 4 out of 44 and a PFR(4m) of 1 out of 44. The median overall survival was 195 and 144 days in the metronomic cyclophosphamide arm and megestrol acetate arm, respectively. CONCLUSION: Metronomic cyclophosphamide is well tolerated and provides stable disease in such vulnerable and poor-prognosis cancer patients. This regimen warrants further evaluations.

Transfer of follow-up care to family physicians for early-stage breast cancer.

AIMS: As a result of the rising prevalence of breast cancer and improved adjuvant treatment strategies, oncologists are faced with an ever-increasing workload of providing long-term follow-up care for early-stage breast cancer patients. In order to cope with these growing demands, innovative follow-up strategies are urgently required. MATERIALS AND METHODS: To explore if patient transfer back to the family physician for follow-up was a potential option, a prospective programme of planned discharge was established for all patients who had completed adjuvant chemo/radiotherapy or had started adjuvant endocrine therapy. Patient and family physician information packages were also provided. RESULTS: Between April and August 2005, of the 193 patients assessed for transfer back to the family physician for follow-up care, transfer was possible in 43%. Fifty-seven per cent (or 110 patients) were unsuitable for transfer back to the family physician. The reasons cited among those deemed unsuitable for transfer were as follows: clinical trial enrollment (50.9%), ongoing endocrine treatment (31.8%), new symptoms (6.3%), and patient refusal (0.9%). In both discharged and non-discharged groups, patients were also frequently being followed by other oncologists (surgical and/or radiation). CONCLUSION: Transfer of care back to family physicians for follow-up may offer a strategy to control workload volumes, and thus enable oncologists to focus their efforts on newly diagnosed and advanced-stage patients with more complex patient care needs.

Chemotherapy-induced amenorrhea: influence on disease-free survival and overall survival in receptor-positive premenopausal early breast cancer patients.

BACKGROUND: The aim of this study was to evaluate the influence of early chemotherapy-induced amenorrhea (CIA) on disease-free survival and overall survival in premenopausal patients with receptor-positive early breast cancer treated with adjuvant chemotherapy without any hormonotherapy. PATIENTS AND METHODS: Retrospectively, we reviewed data from 130 premenopausal patients with localized hormone-sensitive breast cancer. These patients were treated between 1985 and 1995 at the same institution. They all underwent a loco-regional treatment and adjuvant chemotherapy. Early CIA was defined as an amenorrhea arising during the first year following the beginning of chemotherapy. Predictors of early CIA were examined. The survival analyses were done using the Kaplan-Meier method and Cox analysis. RESULTS: Median follow-up was 9 years. Mean age was 42.9 +/- 5 years. Ninety-two per cent of patients had histologically-proven positive axillary nodes. Adjuvant chemotherapy contained no anthracycline in 63%. Early CIA occurred during or after adjuvant chemotherapy in 57% of the patients. It was definitive in 91%. In our study, age was the only CIA predictor in univariate analysis. Women who experienced early CIA tend to have a longer disease-free survival, but the difference was not significant. This trend was lost in multivariate analysis, most probably due to the small sample size. The overall survival was not different. CONCLUSION: Although not statistically significant, our results on a very selected population of patients suggest that a chemotherapy-induced amenorrhea might have its own therapeutic effect besides the cytotoxic action of chemotherapy.