Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS).

BACKGROUND: Acute myeloid leukemia (AML) is fatal in elderly patients who are unfit for standard induction chemotherapy. The objective of this study was to evaluate the survival benefit of administering sapacitabine, an oral nucleoside analogue, in alternating cycles with decitabine, a low-intensity therapy, to elderly patients with newly diagnosed AML. METHODS: This randomized, open-label, phase 3 study (SEAMLESS) was conducted at 87 sites in 11 countries. Patients aged ≥70 years who were not candidates for or chose not to receive standard induction chemotherapy were randomized 1:1 to arm A (decitabine in alternating cycles with sapacitabine) received 1-hour intravenous infusions of decitabine 20 mg/m2 once daily for 5 consecutive days every 8 weeks (first cycle and subsequent odd cycles) and sapacitabine 300 mg twice daily on 3 consecutive days per week for 2 weeks every 8 weeks (second cycle and subsequent even cycles) or to control arm C who received 1-hour infusions of decitabine 20 mg/m2 once daily for 5 consecutive days every 4 weeks. Prior hypomethylating agent therapy for preexisting myelodysplastic syndromes or myeloproliferative neoplasms was an exclusion criterion. Randomization was stratified by antecedent myelodysplastic syndromes or myeloproliferative neoplasms, white blood cell count (<10 × 109 /L and ≥10 × 109 /L), and bone marrow blast percentage (≥50% vs <50%). The primary end point was overall survival (OS). Secondary end points were the rates of complete remission (CR), CR with incomplete platelet count recovery, partial remission, hematologic improvement, and stable disease along with the corresponding durations, transfusion requirements, number of hospitalized days, and 1-year survival. The trial is registered at ClinicalTrials.gov (NCT01303796). RESULTS: Between October 2011 and December 2014, 482 patients were enrolled and randomized to receive decitabine administered in alternating cycles with sapacitabine (study arm, n = 241) or decitabine monotherapy (control arm, n = 241). The median OS was 5.9 months on the study arm versus 5.7 months on the control arm (P = .8902). The CR rate was 16.6% on the study arm and 10.8% on the control arm (P = .1468). In patients with white blood cell counts <10 × 109 /L (n = 321), the median OS was higher on the study arm versus the control arm (8.0 vs 5.8 months; P = .145), as was the CR rate (21.5% vs 8.6%; P = .0017). CONCLUSIONS: The regimen of decitabine administered in alternating cycles with sapacitabine was active but did not significantly improve OS compared with decitabine monotherapy. Subgroup analyses suggest that patients with baseline white blood cell counts <10 × 109 /L might benefit from decitabine alternating with sapacitabine, with an improved CR rate and the convenience of an oral drug. These findings should be prospectively confirmed.

Pixantrone plus rituximab versus gemcitabine plus rituximab in patients with relapsed aggressive B-cell non-Hodgkin lymphoma not eligible for stem cell transplantation: a phase 3, randomized, multicentre trial (PIX306).

PIX306 was a phase 3, randomised, single-blind, multicentre trial conducted in adult patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) grade 3 who relapsed after ≥1 rituximab-containing regimen and were not eligible for a stem cell transplant. Patients were randomised 1:1 to pixantrone 50 mg/m2 or gemcitabine 1000 mg/m2 on days 1, 8 and 15 of a 28-day cycle, combined with rituximab 375 mg/m2 on day 1, for up to six cycles. Patients were followed for up to 96 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), complete response (CR) rate, overall response rate (ORR) and safety. Overall, 312 patients were randomised (median age 73·0 years). The study did not meet its primary endpoint. Median PFS [95% confidence interval (CI)] was 7·3 months (5·2-8·4) with pixantrone + rituximab (PIX + R) and 6·3 months (4·4-8·1) with gemcitabine + rituximab [GEM + R; hazard ratio (HR): 0·85; 95% CI 0·64-1·14; P = 0·28]. Median OS was 13·3 (10·1-19·8) months with PIX + R and 19·6 (12·4-31·9) months with GEM + R (HR: 1·13; 95% CI 0·83-1·53). ORR was 61·9% and 43·9% respectively and CR rate 35·5% and 21·7%. The incidence of adverse events, including cardiac events, was not statistically significant different between PIX + R and GEM + R.

Impact of Primary Ambulatory Thromboprophylaxis (PATP) with Low-Molecular Weight Heparins (LMWHs) on Survival in Patients with Lung Cancer Receiving Chemotherapy.

Lung cancer (LC) is the leading cause of cancer mortality. PATP was provided in experimental trials to decrease the venous thromboembolism (VTE), with ultimate aim to improve overall survival (OS). We undertook an updated systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the impact of PATP with LMWHs on OS and VTE in patients with LC. 5443 patients with LC from nine RCTs were included. The pooled hazard ratio (HR) for OS was 1.02 (95% CI 0.83 to 1.26; P = 0.83) and for progression or metastasis-free survival was 1.03 (95% CI 0.86 to 1.24; P = 0.74). The pooled risk ratio (RR) for VTE was 0.54 (95% CI 0.43 to 0.69; P < 0.00001) and the risk difference (RD) was-0.03 (- 0.05 to - 0.02; P < 0.00001). Our analysis showed no survival advantage with the addition of PATP with LMWHs to standard chemotherapy in patients with LC, regardless of histology or stages of small cell LC.

Dasatinib-Induced T-Cell-Mediated Colitis: A Case Report and Review of the Literature.

Dasatinib is a potent inhibitor of the altered tyrosine kinase activity in disease states associated with BCR/ABL1. This agent has been shown to exhibit broad off-target kinase inhibition and immunomodulating properties. These effects may be responsible for dasatinib's unique side effects including a distinctive form of hemorrhagic colitis. We report a case of hemorrhagic colitis associated with dasatinib use in a patient with chronic myelogenous leukemia. Colon biopsies at the time of symptomatic colitis confirmed CD3+CD8+ T cell infiltration. The process rapidly resolved following drug discontinuation, but relapsed when rechallenged with a reduced dose of dasatinib. Colitis did not recur when the patient was treated with an alternative agent. A literature review of prior cases involving dasatinib-induced T-cell mediated colitis provides insight into commonalities that may facilitate the recognition and management of this entity. Most incidences occurred after a 3-month drug exposure and may be accompanied by large granular lymphocytes. The process uniformly resolves within a few days following drug discontinuation and will generally recur in a shorter period of time if the drug is reintroduced. Most patients will require an alternative agent, although select patients could be continued on dasatinib if other options are limited.

Pixantrone-rituximab versus gemcitabine-rituximab in relapsed/refractory aggressive non-Hodgkin lymphoma.

UNLABELLED: We describe the rationale and design of the ongoing randomized, active-controlled, multicenter, Phase III study evaluating the efficacy of pixantrone and rituximab versus gemcitabine and rituximab in patients with diffuse large B-cell lymphoma or follicular grade 3 lymphoma, who are ineligible for high-dose chemotherapy and stem cell transplantation, and who failed front-line regimens containing rituximab. The administration schedule is pixantrone 50 mg/m(2) intravenously (iv.) or gemcitabine 1000 mg/m(2) iv. on days 1, 8 and 15, combined with rituximab 375 mg/m(2) iv. on day 1, up to six cycles. Pixantrone has a conditional European marketing approval for monotherapy in adults with multiple relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Our trial explores the efficacy of combining pixantrone with rituximab and completes postauthorization measures. TRIAL REGISTRATION NUMBER: NCT01321541.

Results of a phase II study of bendamustine and ofatumumab in untreated indolent B cell non-Hodgkin's lymphoma.

The efficacy/tolerability of bendamustine, a unique alkylator, plus ofatumumab, a human anti-CD20 monoclonal antibody, was evaluated for previously untreated indolent B cell non-Hodgkin's lymphoma (NHL). The study investigated whether the overall response rate (ORR) for bendamustine-ofatumumab was similar to historical bendamustine-rituximab ORRs (≥90 %). In this multicenter, open-label, single-arm, phase II study, patients received six planned 28-day cycles of bendamustine (90 mg/m(2) on days 1 and 2 of each cycle) and ofatumumab (300 mg on day 1, 1000 mg on day 8 of cycle 1, and on day 1 of subsequent cycles). The primary outcome was ORR. Secondary objectives included safety and tolerability. Exploratory evaluations included percentage of patients with positive baseline [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans who converted to negative postbaseline and quality of life (QOL) scores. The treated/safety analysis population received ≥1 dose of either therapy. The bendamustine-ofatumumab ORR was 90 % (95 % confidence interval, 77.8-96.6) in 49 treated patients (67 % complete response, 22 % partial response). No patients had progressive disease. Bendamustine-ofatumumab was acceptably tolerated. All 49 patients had ≥1 adverse event, the most common being nausea (61 %), fatigue (55 %), and infusion-related reactions (45 %, all but 1 occurring during cycle 1). The proportion of patients whose FDG-PET scans converted to negative postbaseline was 88 %. Changes in QOL scores were minor. In patients with treatment-naive, indolent B cell NHL, bendamustine-ofatumumab exhibited a high degree of activity (90 % ORR), comparable with historical bendamustine-rituximab ORRs (≥90 %), and was adequately tolerated ( ClinicalTrials.gov identifier: NCT01108341).

Phase I trial of intravenous fenretinide (4-HPR) plus safingol in advanced malignancies.

PURPOSE: Fenretinide (4-HPR) is a synthetic retinoid that induces cytotoxicity through dihydroceramide production. Safingol, a stereochemical-variant dihydroceramide precursor, exhibits synergistic effects when administered with fenretinide in preclinical studies. We conducted a phase 1 dose-escalation clinical trial of this combination. METHODS: Fenretinide was administered as a 600 mg/m2 24-h infusion on Day 1 of a 21-day cycle followed by 900 mg/m2/day on Days 2 and 3. Safingol was concurrently administered as a 48-h infusion on Day 1 and 2 using 3 + 3 dose escalation. Primary endpoints were safety and maximum tolerated dose (MTD). Secondary endpoints included pharmacokinetics and efficacy. RESULTS: A total of 16 patients were enrolled (mean age 63 years, 50% female, median three prior lines of therapy), including 15 patients with refractory solid tumors and one with non-Hodgkin lymphoma. The median number of treatment cycles received was 2 (range 2-6). The most common adverse event (AE) was hypertriglyceridemia (88%; 38% ≥ Grade 3), attributed to the fenretinide intralipid infusion vehicle. Other treatment-related AEs occurring in ≥ 20% of patients included anemia, hypocalcemia, hypoalbuminemia, and hyponatremia. At safingol dose 420 mg/m2, one patient had a dose-limiting toxicity of grade 3 troponinemia and grade 4 myocarditis. Due to limited safingol supply, enrollment was halted at this dose level. Fenretinide and safingol pharmacokinetic profiles resembled those observed in monotherapy trials. Best radiographic response was stable disease (n = 2). CONCLUSION: Combination fenretinide plus safingol commonly causes hypertriglyceridemia and may be associated with cardiac events at higher safingol levels. Minimal activity in refractory solid tumors was observed. TRIAL REGISTRATION NUMBER: NCT01553071 (3.13.2012).

Meta-analysis of randomized controlled trials on primary ambulatory thromboprophylaxis in patients with nonpancreatic gastrointestinal cancers receiving chemotherapy.

Primary ambulatory thromboprophylaxis (PATP) in patients with solid malignancies is not routinely indicated. We performed a meta-analysis of randomized controlled trials (RCTs) to determine the benefit and risk of PATP in patients with nonpancreatic gastrointestinal cancers receiving chemotherapy. RCTs with venous thromboembolism (VTE) reduction as primary or secondary endpoints were included. A total of 1932 patients from subgroups of 3 RCTs were eligible. The VTE incidence was 1.26% and 2.55% in PATP and control arms, respectively (risk ratio 0.49; confidence interval 0.25 to 0.96; P = 0.04), with a number needed to treat of 78 to prevent one VTE event. In gastric and gastroesophageal junction cancer patients, the VTE incidence was 1.37% and 3.40% in PATP and control arms, respectively (risk ratio 0.40; confidence interval 0.13 to 1.24; P = 0.11). PATP should not be recommended in patients with nonpancreatic gastrointestinal cancers on chemotherapy.

Pomalidomide, dexamethasone, and daratumumab immediately after lenalidomide-based treatment in patients with multiple myeloma: updated efficacy, safety, and health-related quality of life results from the phase 2 MM-014 trial.

Patients with relapsed/refractory multiple myeloma (RRMM) need proven subsequent therapies after early-line lenalidomide treatment failure. The phase 2 MM-014 trial (NCT01946477) investigated pomalidomide, dexamethasone, and daratumumab after 1 to 2 prior treatment lines (62.5%, 1 prior line) in patients with RRMM and prior lenalidomide (75.0%, lenalidomide refractory). With a median follow-up of 28.4 months, overall response rate was 77.7% (52.7% achieved very good partial response or better) and median progression-free survival was 30.8 months. For patients with lenalidomide-refractory disease, these outcomes were 76.2%, 47.6%, and 23.7 months, respectively. No new safety signals were observed; 64.3% experienced grade 3/4 neutropenia. Health-related quality of life was preserved or trended toward improvement through 12 treatment cycles. Pomalidomide, dexamethasone, and daratumumab given immediately after early-line lenalidomide-based treatment continues to demonstrate safety and efficacy, supporting pomalidomide-dexamethasone as a foundation of combination therapy in RRMM and providing evidence that the immunomodulatory agent class delivers benefit after lenalidomide treatment failure.

Sequential Complications of Hypercalcemia, Necrotizing Granulomatous Vasculitis, and Aplastic Anemia Occurring in One Patient with Angioimmunoblastic T-cell Lymphoma.

In this case report of a patient with angioimmunoblastic T-cell lymphoma (AITL), we describe the occurrence of three sequential complications that have been reported uncommonly in this disease subtype. Firstly, the patient developed hypercalcemia due to elevated 1,25-didydroxyvitamin D. Although hypercalcemia in AITL is not rare (1-2% incidence), this case was unusual in that the complication developed when disease appeared stable and symptomatically, he was doing well otherwise. Hypercalcemia surprisingly resolved a few months later at a time when his disease appeared to be progressing. A year later, the patient presented with digital ischemia necessitating partial amputation of a finger. Pathological exam revealed granulomatous vasculitis of small and medium arterioles with infiltrating malignant T lymphocytes. Although skin manifestations are common in AITL, necrotizing granulomatous vasculitis with accompanying tumor cells leading to severe digital ischemia appears rare. Subsequently the patient developed profound pancytopenia with bone marrow confirming severe aplastic anemia. To our knowledge only one other case of aplastic anemia has been reported in a patient with AITL. We discuss the diagnostic and management considerations involved in this patient care and review similar reported cases.

Intracranial atherosclerotic disease: an update.

The consensus conference on intracranial atherosclerosis provides a comprehensive review of the existing literature relevant to the epidemiology, diagnosis, prevention, and treatment of intracranial atherosclerosis, and identifies principles of management and research priorities. Patients who have suffered a stroke or transient ischemic attack attributed to stenosis (50-99%) of a major intracranial artery face a 12 to 14% risk for subsequent stroke during the 2-year period after the initial ischemic event, despite treatment with antithrombotic medications. The annual risk for subsequent stroke may exceed 20% in high-risk groups. In patients with intracranial atherosclerotic disease, short-term and long-term anticoagulation is not superior to antiplatelet treatment. Overall, the subgroup analyses from randomized trials provide evidence about benefit of aggressive atherogenic risk factor management. Intracranial angioplasty with or without stent placement has evolved as a therapeutic option for patients with symptomatic intracranial atherosclerotic disease, particularly those with high-grade stenosis with recurrent ischemic symptoms, medication failure, or both. A multicenter randomized trial is currently under way to compare stent placement with intense medical management for patients with high-grade symptomatic intracranial atherosclerotic disease.

Pomalidomide, dexamethasone, and daratumumab in relapsed refractory multiple myeloma after lenalidomide treatment.

Patients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM) after one to two prior treatment lines in the phase 2 MM-014 study. Patients received pomalidomide 4 mg daily from days 1-21 and dexamethasone 40 mg weekly (28-day cycles). Daratumumab 16 mg/kg was administered per label. Primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. Per protocol, all patients (N = 112) had received lenalidomide in their most recent prior regimen (75.0% lenalidomide refractory). ORR was 77.7% (76.2% in lenalidomide-refractory patients); median follow-up was 17.2 months. Median PFS was not reached (1-year PFS rate 75.1%). The most common hematologic grade 3/4 treatment-emergent adverse event was neutropenia (62.5%). Grade 3/4 infections were reported in 31.3% of patients, including 13.4% with grade 3/4 pneumonia. These results demonstrate the safety and efficacy of pomalidomide-based therapy as early as second line in patients with RRMM, even immediately after lenalidomide failure, indicating that switching from the immunomodulatory agent class is not necessary.

Case report of two siblings with type 2A von Willebrand disease involving a novel mutation within the calcium-binding site of the A2 domain of von Willebrand factor.

: Calcium-binding at the A2 domain protects von Willebrand factor (VWF) from cleavage by a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS13) and is coordinated by five important residues (p.Asp1596, p.Arg1597, p.Ala1600, p.Asn1602, and p.Asp1498). Only variants of p.Arg1597 resulting in type 2A von Willebrand disease have been reported. We report a novel VWF variant, a heterozygous single nucleotide change, c.4493A>G, occurring at the p.Asp1498 residue of the calcium-binding site of the A2 domain in two sisters with type 2A von Willebrand disease. Modest increase in the VWF propeptide/VWF:Ag ratio (2.4 and 2.7) supports increased clearance of VWF. A literature review provided insight into the integral role of p.Asp1498 residue in calcium-binding and its role in the stabilization of other residues including p.Arg1597 and p.Asn1602. Studies done by other groups on engineered mutations involving p.Asp1498 reported increased susceptibility to ADAMTS13 proteolysis. Cellular studies are needed to confirm these mechanisms.

Safety analysis of repeated high doses of samarium-153 lexidronam in men with hormone-naive prostate cancer metastatic to bone.

PURPOSE: The safety and tolerability of repetitive doses of the boneseeking radiopharmaceutical samarium-153 lexidronam (153Sm- EDTMP) were investigated in men with hormone-naive prostate cancer metastatic to bone. PATIENTS AND METHODS: Within 30 days of initiating androgen deprivation, the first of 4 planned doses of 153Sm- EDTMP given every 12 weeks was administered. Growth factors were not permitted. The first cohort of 6 patients received 153Sm-EDTMP at 2 mCi/kg per dose; 3 patients completed all 4 doses and 3 received 3 doses. RESULTS: There were 7 episodes of grade 3 neutropenia and 1 each of grade 3 and 4 thrombocytopenia. Of 6 patients in the second cohort who received 153Sm-EDTMP 2.5 mCi/kg per dose, only 1 received all 4 doses. Four events of grade 3 neutropenia and 2 events of grade 3 thrombocytopenia were reported. The 12-week dose schedule resulted in persistent low-grade thrombocytopenia and/or leukopenia, which prevented administration of all 4 planned doses. As a result, the dose of 153Sm-EDTMP was decreased to 2 mCi/kg for a total of 3 doses administered every 16 weeks. Five of 6 patients in this cohort received all 3 doses of 153Sm-EDTMP. There were 7 episodes of reversible grade 3 neutropenia. For all 18 patients on the study, there were no drug-related serious adverse events or grade 4 nonhemmatologic toxicities. CONCLUSION: In men with hormone-naive prostate cancer metastatic to bone, the feasible dose and schedule for repeated doses of 153Sm-EDTMP is 2 mCi/kg given every 16 weeks for 3 doses.

Consensus conference on intracranial atherosclerotic disease: rationale, methodology, and results.

The consensus conference on intracranial atherosclerotic disease (ICAD) identifies principles of management, and research priorities in various aspects upon which leading experts can agree (using "Delphi" method). ICAD is more prevalent in Asian, Hispanic, and African-American populations. Patients who have had a stroke or transient ischemic attack (TIA) attributed to stenosis (50-99%) of a major intracranial artery face a 12-14% risk of subsequent stroke during the 2-year period after the initial ischemic event, despite treatment with antithrombotic medications. The annual risk of subsequent stroke may exceed 20% in high-risk groups. The medical treatment of patients with symptomatic ICAD is directed toward: 1. Prevention of intraluminal thrombo-embolism, 2. plaque stabilization and regression, and 3. management of atherogenic risk factors. In patients with ICAD, short-term and long-term anticoagulation (compared with aspirin) have not shown to be beneficial. The current guidelines recommend that aspirin monotherapy, the combination of aspirin and extended release dipyridamole, and clopidogrel monotherapy (rather than oral anticoagulants) are all acceptable options in patients with non-cardioembolic ischemic stroke and TIA. Overall, the subgroup analysis from randomized trials provides evidence about benefit of aggressive atherogenic risk factor management among patients with ICAD. Intracranial angioplasty with or without stent placement has evolved as a therapeutic option for patients with symptomatic ICAD, particularly those with high-grade stenosis with recurrent ischemic symptoms and/or medication failure. A matched comparison between medical-treated patients in the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) study and stent-treated patients in the National Institutes of Health intracranial stent registry concluded that stent placement may offer benefit in patients with 70-99% stenosis. The 5-year, multicenter, prospective, randomized Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis study supported by the National Institutes of Health is currently comparing stent placement with intense medical management with intense medical management alone in patients with high-grade symptomatic intracranial stenosis. The proceedings of the consensus conference provide a template for standardizing management of patients with ICAD and determining research priorities.

Safety and efficacy of repeat administration of samarium Sm-153 lexidronam to patients with metastatic bone pain.

BACKGROUND: Samarium Sm 153 lexidronam (Sm-153) is an effective and well-tolerated treatment for painful bone metastases. The purpose of the analysis was to assess the safety and efficacy of repeated doses of Sm-153 in patients with metastatic bone pain. METHODS: Data were collected prospectively for 202 patients administered 1.0 mCi/kg of Sm-153. Particular emphasis was placed on analysis of data from 55 patients receiving > or = 2 doses. Pain scores, adverse events, and hematologic parameters were assessed after each dose. RESULTS: Mild, transient suppression of platelets and white blood cell counts was the most common adverse event after treatment. Nadirs were approximately half of baseline at 4 weeks after dosing with recovery by Week 8 in 90% of patients. Temporary grade 3 thrombocytopenia occurred in 11%, 12%, and 17% of patients after the first, second, and third drug administration, respectively. Grade 3 leukopenia occurred in less than 7% of patients independent of the number of administrations. Significant decreases in pain scores (P < .001) were observed at Week 4 after each of the first 3 doses and maintained at Week 8 after the first 2 doses (P < .003) but not the third. Decreases in pain scores were observed in 70%, 63%, and 80% of patients, respectively, at Week 4 after the first 3 administrations. CONCLUSIONS: Repeated dosing of 1.0 mCi/kg of Sm-153 was both safe and effective and is a reasonable treatment option in patients whose bone pain responds and then recurs after an initial dose provided that adequate hematologic function is present at the time of drug administration.

Locally advanced prostate cancer treated with concomitant radiation and 5-fluorouracil: Southwest Oncology Group Study 9024.

PURPOSE: Radiation is considered the standard treatment for locally advanced (T3 and T4) prostate cancer but cure with radiation alone is infrequent. Studies have shown that adding androgen ablation improves the results but there is still much room for improvement. We performed a phase II multi-institutional study to explore the feasibility of concomitant chemoradiotherapy. MATERIALS AND METHODS: Eligible patients had prostate cancer with clinical evidence of invasion through the prostatic capsule or into the seminal vesicles without evidence of nodal or distant metastasis. Prior prostatectomy was not allowed and patients could not be candidates for surgical resection due to medical reasons or refusal of surgery. Radiation consisted of 7,020 cGy in 39 fractions. Continuous infusion 5-fluorouracil at a dose of 200 mg/m2 daily was started on day 1 and continued 7 days weekly until the last day of radiation. RESULTS: All 30 eligible patients were evaluated for toxicity. Diarrhea was the most common toxicity with grade 3 and 4 diarrhea in 2 and 1 patients, respectively. The only other grade 4 toxicity was hemorrhagic cystitis in 1 patient. There was 1 incident each of grade 3 stomatitis, congestive heart failure, edema, proctitis and hematuria. No patient with grade 3 or 4 toxicity required treatment delay. Ten patients (33%) achieved a negative biopsy and 13 (43%) achieved prostate specific antigen less than 1.0 ng/ml. Six patients (20%) achieved a complete response, defined as negative biopsy and prostate specific antigen less than 1.0 (95% CI 8 to 39). Patients without any biopsies or without prostate specific antigen followup were assumed to be nonresponders. CONCLUSIONS: Toxicity was acceptable. The modest response rate indicates that better chemotherapy that improves local and systemic failure is necessary to improve the results. This study confirms the feasibility of a combined chemoradiotherapy approach.

Evaluation of an anesthetic pump for postoperative care after shoulder surgery.

In theory, a prolonged, local infusion of anesthetic into a surgical field should reduce postoperative pain. Recently, disposable products have become available to implement this, but the balance between cost and benefit is controversial. This study evaluated such a device in two specific types of arthroscopic surgery of the shoulder: decompression of the subacromial space and repair of a torn labrum in the glenohumeral joint. Placement of the catheter into the glenohumeral joint resulted in problems in removing the device from some cases so that application is not recommended. When the catheter was placed in the subacromial space, the infusion pump was associated with significantly shorter stays in the recovery room, but there was no benefit over placebo with regard to pain, demand for rescue narcotic, or recovery of motion. Furthermore, use of the device presented some inconveniences to the surgical staff and the patient. It was concluded that use of this particular device in these particular applications is not justified.