Cancer patients with fractures are rarely assessed or treated for osteoporosis: a population-based study.

Among 4238 cancer and 16,418 cancer-free individuals with incident major non-traumatic fractures (hip, clinical vertebral, forearm, humerus), post-fracture osteoporosis care was equally poor for both groups, whether assessed from bone mineral density (BMD) testing, initiation of osteoporosis therapy or either intervention (BMD testing and/or osteoporosis therapy). INTRODUCTION: Most individuals sustaining a fracture do not undergo evaluation and/or treatment for osteoporosis. Cancer survivors are at increased risk for osteoporosis and fracture. Whether cancer survivors experience a similar post-fracture "care gap" is unclear. Using population-based databases, we assessed whether cancer patients are evaluated and/or treated for osteoporosis after a major fracture. METHODS: From the Manitoba Cancer Registry, we identified cancer cases (first cancer diagnosis between 1987 and 2013) and cancer-free controls with incident major non-traumatic fractures (from provincial physician billing claims and hospitalization databases). The outcomes were performance of BMD testing (from the BMD Registry), initiation of osteoporosis therapy (from drug dispensation database) or either intervention (BMD testing and/or osteoporosis therapy) in the 12 months post-fracture. RESULTS: There were 4238 cancer and 16,418 cancer-free individuals who sustained a fracture after the index date (cancer diagnosis) and were followed for at least 1 year post-fracture. Subsequent BMD testing was performed in 11.0% of cancer cases versus 11.5% non-cancer controls (P = 0.43), osteoporosis treatment in 22.9% cancer cases versus 21.8% non-cancer controls (P = 0.15), and either testing or treatment in 28.9% cancer cases versus 28.4% non-cancer controls (P = 0.53). Predictors of BMD testing and/or initiation of therapy were similar for non-cancer and cancer patients. Post-fracture interventions were consistently used more frequently among women, older patients (age 50 years or older), those who sustained fractures in a later calendar period, and (for treatment) after vertebral fracture. Cancer-specific variables (cancer type, years from cancer diagnosis to fracture, specialty of care provider) showed only weak and inconsistent effects. CONCLUSIONS: A large care gap exists among cancer patients who sustain a fracture, similar to the general population, whereby the evaluation or treatment for osteoporosis is seldom conducted. Care maps may need to be developed for cancer populations to improve post-fracture care.

Baseline Edmonton Symptom Assessment System and survival in metastatic renal cell carcinoma.

Background: Baseline symptom burden as measured using the Edmonton Symptom Assessment System (esas), a patient-reported, validated, and reliable tool measuring symptom severity in 9 separate domains, might yield prognostic information in patients receiving treatment for metastatic renal cell carcinoma (mrcc) and might add to the existing prognostic models. Methods: In this retrospective single-centre cohort study, we included patients receiving first-line sunitinib therapy for mrcc between 2008 and 2012. Baseline variables included information relevant to the pre-existing prognostic models and pre-treatment esas summation scores (added together across all 9 domains), with higher scores representing greater symptom burden. We used Kaplan-Meier curves and Cox regression modelling to determine if symptom burden can provide prognostic information with respect to overall survival. Results: We identified 68 patients receiving first-line therapy for mrcc. Most had intermediate- or poor-risk disease based on both the Memorial Sloan Kettering Cancer Center (mskcc) and the International Metastatic Renal Cell Carcinoma Database Consortium (imdc) models. The median baseline esas summation score was 16 (range: 6-57). In univariable analysis, the hazard ratio for overall survival was 1.270 (p = 0.0047) per 10-unit increase in summation esas. In multivariable analysis, the hazard ratio was 1.208 (p = 0.0362) when controlling for mskcc risk group and 1.240 (p = 0.019) when controlling for imdc risk group. Conclusions: Baseline symptom burden as measured by esas score appears to provide prognostic information for survival in patients with mrcc. Those results should encourage the investigation of patient-reported symptom scales as potential prognostic indicators for patients with advanced cancer.

Adolescent and young adult cancer: principles of care.

Adolescents and young adults (ayas) with cancer in active treatment face a number of barriers to optimal care. In the present article, we focus on the 3 critical domains of care for ayas-medical, psychosocial, and research-and how changes to the system could overcome barriers. We summarize the current literature, outline recommended principles of care, raise awareness of barriers to optimal care, and suggest specific changes to the system to overcome those barriers in the Canadian context. Many of the recommendations can nevertheless be applied universally. These recommendations are endorsed by the Canadian Task Force on Adolescents and Young Adults with Cancer and build on outcomes from two international workshops held by that group.

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.

Assessment and management of febrile neutropenia in emergency departments within a regional health authority-a benchmark analysis.

OBJECTIVES: Febrile neutropenia is considered an oncologic emergency, for which prompt initiation of antibiotics is essential. METHODS: We conducted a retrospective cohort study for the 2006 calendar year involving all adult oncology patients presenting with febrile neutropenia to a regional health authority's emergency departments. The objective was to determine the time from triage to antibiotic administration and its impact on patient outcomes. RESULTS: We identified 68 patients presenting with febrile neutropenia, most of whom (76%) were seen in tertiary care centers. Of those patients, 65% were triaged to be seen within 15 minutes of arrival in the emergency room; however, the median time to reassessment was 57 minutes. The median time from triage to antibiotic administration was 5 hours (range: 1.23-22.8 hours). No increased risk of death or increased length of hospital stay was associated with delayed antibiotic administration. Older patients and patients without caregiver support were more likely to experience delayed antibiotic administration (odds ratio: 3.8 and 12.7 respectively). CONCLUSIONS: We were not able to show a deleterious effect of delay in antibiotic administration, but our analysis identified several points at which patient flow through the emergency room could be improved.

A comprehensive bone-health management approach for men with prostate cancer receiving androgen deprivation therapy.

For advanced and metastatic prostate cancer, androgen deprivation therapy (adt) is the mainstay of treatment. Awareness of the potential bone-health complications consequent to adt use is increasing. Many studies have shown that prolonged adt leads to significant bone loss and increased fracture risk that negatively affect quality of life. Clinical practice guidelines for preserving bone health in men with prostate cancer on adt vary across Canada. This paper reviews recent studies on bone health in men with prostate cancer receiving adt and the current evidence regarding bone-health monitoring and management in reference to Canadian provincial guidelines. Based on this narrative review, we provide general bone-health management recommendations for men with prostate cancer receiving adt.

Preclinical and clinical activity of sunitinib in patients with cisplatin-refractory or multiply relapsed germ cell tumors: a Canadian Urologic Oncology Group/German Testicular Cancer Study Group cooperative study.

BACKGROUND: The objective of the study was to investigate the activity of sunitinib in a cell line model and subsequently in patients with cisplatin-refractory or multiply relapsed germ cell tumors (GCT). METHODS: The effect of sunitinib on cell proliferation in cisplatin-sensitive and cisplatin-refractory GCT cell lines was evaluated after 48-h sunitinib exposure by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, and IC(50) (concentration that causes 50% inhibition of growth) doses were determined. Sunitinib was subsequently administered at a dose of 50 mg/day for 4 weeks followed by a 2-week break to 33 patients using a Simon two-stage design. RESULTS: Sunitinib demonstrated comparable dose-dependent growth inhibition in cisplatin-sensitive and cisplatin-resistant cell lines, with IC(50) between 3.0 and 3.8 µM. Patient characteristics were as follows: median of 2 (1-6) cisplatin-containing regimens; high-dose chemotherapy 67%; late relapse 33%; and cisplatin refractory or absolute cisplatin refractory 54%. Toxic effects included fatigue (39%), anorexia (21%), diarrhea (27%), mucositis (45%), nausea (33%), hand-foot syndrome (12%), dyspepsia (27%), and skin rash (18%). No unexpected side-effects were observed. Thirty -two of 33 patients were assessable for response. Three confirmed partial responses (PRs) and one unconfirmed PR were seen for a total response rate of 13%. Median progression-free survival (PFS) was 2 months, with a 6-month PFS rate of 11%. CONCLUSIONS: Sunitinib shows in vitro activity in cisplatin-resistant GCT cell lines. Modest clinical activity in heavily pretreated GCT patients was observed.

Long-term follow-up of patients undergoing auto-SCT for advanced germ cell tumour: a multicentre cohort study.

Failure of cisplatin-based chemotherapy in advanced germ cell tumour (GCT) is associated with a poor outcome. High-dose chemotherapy and auto-SCT is one therapeutic option, although the long-term outcome after this procedure is unclear. We conducted a multicentre cohort study of consecutive patients undergoing a single auto-SCT for GCT between January 1986 and December 2004. Of 71 subjects, median follow-up is 10.1 years. OS at 5 years is 44.7% (95% confidence interval (CI) 32.9-56.5%) and EFS is 43.5% (95% CI 31.4-55.1%). There were seven (10%) treatment-related deaths within 100 days of auto-SCT. Three (4.2%) patients developed secondary malignancies. Of 33 relapses, 31 occurred within 2 years of auto-SCT. Two very late relapses were noted 13 and 11 years after auto-SCT. In multivariate analysis, favourable outcome was associated with IGCCC (International Germ Cell Consensus Classification) good prognosis disease at diagnosis, primary gonadal disease and response to salvage chemotherapy. We conclude that auto-SCT results in successful outcome for a relatively large subgroup of patients with high-risk GCT. Late relapses may occur, a finding not previously reported.

A phase II study of sorafenib in patients with chemo-naive castration-resistant prostate cancer.

BACKGROUND: The purpose of this trial was to evaluate the antitumor activity of sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, in patients with castration-resistant prostate cancer. PATIENTS AND METHODS: This was a multicenter, two-stage, phase II study. Sorafenib 400 mg was administered orally twice daily continuously. Primary end point was prostate-specific antigen (PSA) 'response' defined as a > or =50% decrease for > or =4 weeks. RESULTS: In all, 28 patients were enrolled. Eastern Cooperative Oncology Group performance status was zero or one in 19 and 9 patients. Two patients had no metastases, and 26 had bone and/or lymph node disease. A median of two cycles (range 1-8) was delivered. Adverse events were typical for sorafenib. The PSA response rate was 3.6% [95% confidence interval (CI) 0.1% to 18.3%] with response occurring in one patient (baseline = 10 000 and nadir = 1643 microg/l). No measurable disease responses occurred in eight patients. Time to PSA progression was 2.3 months (95% CI 1.8-6.4). Of 16 patients who discontinued sorafenib and then did not receive any immediate therapy, 10 had postdiscontinuation PSA declines of 7%-52%. CONCLUSIONS: Sorafenib has limited activity using current PSA criteria. The declines in PSA observed on treatment discontinuation indicate an effect on PSA production/secretion. Further study may be warranted but needs to consider the limitations of PSA as an indicator of progression and response.

Chemotherapy in small bowel adenocarcinoma: 10-year experience of the British Columbia Cancer Agency.

AIMS: Small bowel adenocarcinoma (SBA) is a rare, frequently lethal, malignancy. Little is known about the use and value of chemotherapy in patients with SBA. We assessed this issue in a consecutive cohort of patients from British Columbia, Canada. MATERIALS AND METHODS: Consecutive patients with SBA seen at the British Columbia Cancer Agency from January 1990 to September 2000 were identified. A retrospective systematic chart review was undertaken and a survival analysis conducted. RESULTS: Forty-eight SBA were identified in 47 subjects. Chemotherapy was given to 21 of the 47 subjects (45%). Of 19 patients treated initially with curative intent, the median overall survival was 38.6 months. Five received adjuvant chemotherapy, with two subsequently recurring. Thirty-seven patients initially or eventually had advanced disease: 16 received 22 palliative intent fluoropyrimidine-based regimens. Only one partial response was seen in the first line (objective response rate 6%). The median overall survival for those who received palliative chemotherapy was 15.6 months compared with 7.7 months for those who did not. CONCLUSIONS: Chemotherapy use is common in SBA. Our data and available published studies suggest that chemotherapy may provide benefit, but the optimal chemotherapy regimen and the degree of benefit remain to be defined. A sound approach to investigate the management of rare malignancies is desperately needed.

Liposomal encapsulated doxorubicin (Caelyx) in the treatment of relapsed aggressive non-Hodgkin's lymphoma: a phase II study.

Aggressive non-Hodgkin's lymphoma (NHL), such as diffuse large B-cell lymphoma, can be cured in approximately 50% of cases, but those cases that recur and are not amenable to high-dose chemotherapy rely on palliative chemotherapy to improve symptoms and prolong life. Anthracyclines are associated with a high response rate in aggressive NHL but extended treatment results in cardiotoxicity. Liposomal encapsulated doxorubicin has been shown in other tumor types to allow for extended treatment with doxorubicin, but is associated with a low cardiac risk. The present study aimed to assess the response rate, survival and cardiac risk of patients with relapsed aggressive NHL treated with liposomal encapsulated doxorubicin. Eighteen patients with relapsed aggressive NHL were treated with liposomal encapsulated doxorubicin (40 - 50 mg/m2) for a planned six cycles. Some 83% of patients had diffuse large B-cell or mantle cell NHL. Four patients had a partial response (23%), whereas five patients had stable disease. None had a complete response. Eight patients progressed when receiving the liposomal encapsulated doxorubicin therapy. The median survival time was 34 weeks, and the median progression-free survival was 15.7 weeks. Overall survival was 50% at 6 months and 39% at 12 months. Progression-free survival was 33% at 6 months and was 28% at 12 months. The mean ejection fraction pre- and post-liposomal encapsulated doxorubicin treatment remained the same. Only one patient had a drop in ejection fraction to <50%. Liposomal encapsulated doxorubicin offers another choice to patients seeking palliation from their lymphoma recurrence with a response rate of 23% that was well tolerated and had a minimal cardiotoxic risk.

CT slice index and thickness: impact on organ contouring in radiation treatment planning for prostate cancer.

OBJECTIVE: To assess the impact of CT slice index and thickness (3 mm versus 5 mm) on (i) prostate volume, dimensions, and isocenter coordinates, (ii) bladder and rectal volumes, and (iii) DRR quality, in the treatment of prostate cancer. METHODS: 16 patients with prostate cancer underwent two planning CT-scans using 3 and 5 mm slice index/thickness. Prostate, bladder, and rectum were outlined on all scans. Prostate isocenter coordinates, maximum dimensions, and volumes were compared along with bladder and rectal volumes. Bladder volumes and maximum diameters were further investigated using a second observer. A comparative analysis of DRR quality was conducted as well as a dosimetric analysis using DVH. RESULTS: The differences in measurements of prostate volume, isocenter coordinates and maximum dimensions between the 3 and 5 mm scans, were small and not statistically significant. Similar finding was seen for rectal volume. However, bladder volume was always larger on the 3 mm scan (mean difference=27.9 cc; SE=4.8 cc; 95% CI: 17.7-38.2 cc; p<0.001) and the findings were reproduced with the second observer (mean difference=31.9 cc; SE=4.7 cc; 95% CI: 21.9-41.9 cc; p<0.001). The differences in volume are caused by a slight increase in (1) the measurement of the longitudinal dimensions on the 3 mm scans, and (2) the slice by slice measured bladder area on the 3 mm scans. The latter is due to partial volume effect. The 3 mm DRR were slightly better than the 5 mm DRR. The bladder DVH differed significantly in some patients. CONCLUSION: Bladder volume is significantly larger on the 3 mm scans. Differences in contoured areas may be accounted for, in part, by the partial volume effect.

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.