The risk of colorectal cancer is not increased after a diagnosis of urothelial cancer: a population-based study.

BACKGROUND: The data about whether patients with a prior urothelial cancer (uca) are at increased risk of colorectal cancer (crc) are conflicting. We used a competing risks analysis to determine the risk of crc after uca. METHODS: Historical cohorts were assembled by record linkage of Manitoba Cancer Registry and Manitoba Health databases. The incidence of crc for individuals with uca as their first cancer between 1987 and 2009 was compared with the incidence for randomly selected age-and sex-matched individuals without a cancer diagnosis at the index date (uca diagnosis date). Three competing outcomes (crc, another primary cancer, and death) were evaluated by competing risks proportional hazards models with adjustment for relevant confounders. RESULTS: The cohorts of 4591 patients with uca and 22,312 without uca were followed for a total of 179,287 person-years (py). After uca, the rate of subsequent colon cancer in uca patients was 4.5 per 1000 py compared with 3.6 per 1000 py in the non-cancer cohort. In the multivariable analysis, no overall increase in crc risk was observed for patients first diagnosed with uca (hazard ratio: 0.88; 95% confidence interval: 0.70 to 1.1; p = 0.26). CONCLUSIONS: Because of similar crc risk, a similar crc screening strategy should be applied for individuals with and without uca.

Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 1: prophylaxis.

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy has been shown to prevent vte; however, unique clinical circumstances in patients with cancer can often complicate the decisions surrounding the administration of prophylactic anticoagulation. No national Canadian guidelines on the prevention of cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin can be used prophylactically in cancer patients at high risk of developing vte. Direct oral anticoagulants are not recommended for vte prophylaxis at this time. Specific clinical scenarios, including renal insufficiency, thrombocytopenia, liver disease, and obesity can warrant modifications in the administration of prophylactic anticoagulant therapy. There is no evidence to support the monitoring of anti-factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, factor Xa levels could be checked at baseline and periodically in patients with renal insufficiency. The use of anticoagulation therapy to prolong survival in cancer patients without the presence of risk factors for vte is not recommended.

Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 2: treatment.

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy is used to treat vte; however, patients with cancer have unique clinical circumstances that can often make decisions surrounding the administration of therapeutic anticoagulation complicated. No national Canadian guidelines on the management of established cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin is the treatment of choice for cancer patients with established vte. Direct oral anticoagulants are not recommended for the treatment of vte at this time. Specific clinical scenarios, including the presence of an indwelling venous catheter, renal insufficiency, and thrombocytopenia, warrant modifications in the therapeutic administration of anticoagulation therapy. Patients with recurrent vte should receive extended (>3 months) anticoagulant therapy. Incidental vte should generally be treated in the same manner as symptomatic vte. There is no evidence to support the monitoring of anti-factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, levels of anti-factor Xa could be checked at baseline and periodically thereafter in patients with renal insufficiency. Follow-up and education about the signs and symptoms of vte are important components of ongoing patient care.

Prostate specific antigen response to mitoxantrone and prednisone in patients with refractory prostate cancer: prognostic factors and generalizability of a multicenter trial to clinical practice.

PURPOSE: We determine prostate specific antigen (PSA) response and durability, and prognostic factors associated with response and survival in patients with symptomatic hormone refractory prostate cancer treated with mitoxantrone and prednisone at a single institution. We then compare the results with those of a randomized phase III clinical trial. MATERIALS AND METHODS: A retrospective review of all 133 patients treated with mitoxantrone and prednisone at Princess Margaret Hospital since 1994 was performed. PSA response and duration, and overall survival were determined as well as the influence of baseline factors on these outcome parameters. Results were compared to those for patients randomized to receive mitoxantrone and prednisone in the Canadian clinical trial which demonstrated palliative benefit of this regimen. RESULTS: Patients treated after trial closure had shorter survival (p = 0.003) but represented a poorer prognosis cohort. PSA response of the trial and post-trial cases was 34% and 28%, respectively (p = 0.36), and median duration of response was 118 and 175 days or greater, respectively. Factors predictive of PSA response in the non-trial cohort were longer time from diagnosis of prostate cancer (p = 0. 027) and higher baseline PSA (p = 0.013). Factors predictive of increased survival in both groups were younger age (p <0.04), better baseline Eastern Cooperative Oncology Group performance status (p <0. 02), and higher hemoglobin (p

High risk of vascular events in patients with urothelial transitional cell carcinoma treated with cisplatin based chemotherapy.

PURPOSE: We define the incidence of thromboembolic events in patients receiving multiagent chemotherapy for urothelial cancer. MATERIALS AND METHODS: A retrospective chart review of 271 consecutive patients who received multi-agent cisplatin based chemotherapy for transitional cell carcinoma at Princess Margaret Hospital between 1986 and 1996 was performed. Indications for chemotherapy included adjuvant treatment following resection of high risk disease (13%), and primary management of locally advanced and metastatic disease (87%). RESULTS: Vascular events occurred in 35 patients (12.9%) receiving chemotherapy, including 18 deep vein thromboses, 9 pulmonary emboli, 7 arterial thromboses, 3 cerebrovascular events, 1 superficial phlebitis and 1 angina pectoris (4 patients had deep vein thrombosis and pulmonary embolus). Three events were directly fatal. Overall, 3.6% of chemotherapy cycles were complicated by vascular events with 27 events (77%) occurring during the first 2 cycles. Risk factors for vascular events included a large pelvic mass and concomitant peripheral vascular or coronary artery disease. Substantial morbidity was associated with vascular events and median hospital stay of 10 days. CONCLUSIONS: There is a substantial risk of venous and arterial vascular events in patients receiving cisplatin based chemotherapy for urothelial transitional cell carcinoma. Prophylactic anticoagulation should be considered in patients with risk factors for thromboembolic disease.

Adjuvant chemotherapy for high-risk urothelial transitional cell carcinoma: the Princess Margaret Hospital experience.

OBJECTIVE: To review the outcome of adjuvant systemic chemotherapy after surgery for patients with locally advanced urothelial transitional cell carcinoma (TCC) of the bladder and upper urinary tract who were at high risk for recurrence or metastatic spread. PATIENTS AND METHODS: Thirty-five patients (27 men and eight women, median age 59 years) received adjuvant chemotherapy and were followed for a median of 31 months from surgery (range 12-109). All patients had undergone surgery (cystectomy, nephrectomy, nephrouretectomy), with removal of all evident tumour from the following primary sites: bladder (29), renal pelvis (three) and ureter (three). Thirty patients had stage pT3 or greater, 22 had node-positive disease and 16 had vascular invasion. The median interval from surgery to chemotherapy was 2 months. Patients received a median of four courses of cisplatin, methotrexate and vinblastine (n = 23) or the same drugs with doxorubicin (n = 12). RESULTS: Toxicity included nine episodes of febrile neutropenia (one fatal) and six episodes of thromboembolism (one fatal). Eighteen patients (51%) remain alive and free of apparent disease with a median follow-up of 31 months. Actuarial overall and relapse-free survival were 64% and 57% at 2 years and 47% and 53% at 5 years, respectively. For the 22 node-positive patients, the median relapse-free survival and overall survival was 22 months and 33 months, respectively. CONCLUSIONS: Patients with urothelial TCC at high risk of relapse after radical surgery can have a reasonable chance of long-term survival with systemic adjuvant chemotherapy. Treatment is associated with toxicity. The benefits of treatment should be addressed in a large randomized controlled trial.

Phase I/II study of the CAPABLE regimen for patients with poorly differentiated carcinoma of the nasopharynx.

PURPOSE: To evaluate the role of aggressive combination chemotherapy in patients with poorly differentiated carcinoma of the nasopharynx (NPC). PATIENTS AND METHODS: In a prospective phase I/II study, 90 chemotherapy-naive patients with NPC (21 with very advanced locoregional disease, 18 with locoregional persistent and/or recurrent disease postradiotherapy, and 51 with metastatic disease) were treated with cyclophosphamide, doxorubicin, cisplatin, methotrexate, and bleomycin (CAPABLE). Two schedules of this regimen were used over a 9-year period, with the second schedule being a modification of the first in an attempt to minimize treatment-related toxicity. RESULTS: Of 21 patients with very advanced local disease, one had a complete response (CR) and 17 had partial responses (PRs) (response rate, 86%). Seventeen of these 21 patients had subsequent radiotherapy. Of 17 patients with measurable locoregional disease either persistent and/or recurrent postradiotherapy, there were four CRs and three PRs (response rate, 41%). Of 44 patients with measurable metastatic disease, there were three CRs and 32 PRs (response rate, 80%). The median survival durations for these three groups of patients were 47, 16, and 14 months, respectively. The two chemotherapy schedules had similar received dose-intensities (RDIs) and produced similar response rates and survival. Toxicity was severe with frequent mucositis and myelosuppression. Overall, 37 patients required at least one hospital admission for management of toxic side effects and there were seven drug-related deaths. Three of the deaths were due to fulminant hepatitis, likely from reactivation of hepatitis B. CONCLUSION: This aggressive regimen provides a high rate of tumor response, but limited palliation for most patients with recurrent or metastatic NPC. The results with chemotherapy followed by radiotherapy for patients with very advanced local disease are encouraging, but proof of benefit would require evaluation in a randomized trial.

A durable response to cytarabine in advanced breast cancer.

Cytarabine is a useful agent in the management of acute leukaemias, but is not thought to have activity in solid tumours. We describe the case history of a woman with advanced breast cancer, presenting with superior vena cava obstruction occurring after radiotherapy and chemotherapy, who had a durable remission following inadvertent dosing with cytarabine. A review of the literature reveals that this is the first documented case of a meaningful response to cytarabine in metastatic breast cancer.