Edward P. Balaban

Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update 2014

PURPOSE To provide current recommendations about the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. METHODS PubMed and the Cochrane Library were searched for randomized controlled trials, systematic reviews, meta-analyses, and clinical practice guidelines from November 2012 through July 2014. An update committee reviewed the identified abstracts. RESULTS Of the 53 publications identified and reviewed, none prompted a change in the 2013 recommendations. RECOMMENDATIONS Most hospitalized patients with active cancer require thromboprophylaxis throughout hospitalization. Routine thromboprophylaxis is not recommended for patients with cancer in the outpatient setting. It may be considered for selected high-risk patients. Patients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone should receive prophylaxis with either low-molecular weight heparin (LMWH) or low-dose aspirin. Patients undergoing major surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Extending prophylaxis up to 4 weeks should be considered in those undergoing major abdominal or pelvic surgery with high-risk features. LMWH is recommended for the initial 5 to 10 days of treatment for deep vein thrombosis and pulmonary embolism as well as for long-term secondary prophylaxis (at least 6 months). Use of novel oral anticoagulants is not currently recommended for patients with malignancy and VTE because of limited data in patients with cancer. Anticoagulation should not be used to extend survival of patients with cancer in the absence of other indications. Patients with cancer should be periodically assessed for VTE risk. Oncology professionals should educate patients about the signs and symptoms of VTE.

Appropriate Chemotherapy Dosing for Obese Adult Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline

PURPOSE To provide recommendations for appropriate cytotoxic chemotherapy dosing for obese adult patients with cancer. METHODS The American Society of Clinical Oncology convened a Panel of experts in medical and gynecologic oncology, clinical pharmacology, pharmacokinetics and pharmacogenetics, and biostatistics and a patient representative. MEDLINE searches identified studies published in English between 1996 and 2010, and a systematic review of the literature was conducted. A majority of studies involved breast, ovarian, colon, and lung cancers. This guideline does not address dosing for novel targeted agents. RESULTS Practice pattern studies demonstrate that up to 40% of obese patients receive limited chemotherapy doses that are not based on actual body weight. Concerns about toxicity or overdosing in obese patients with cancer, based on the use of actual body weight, are unfounded. RECOMMENDATIONS The Panel recommends that full weight-based cytotoxic chemotherapy doses be used to treat obese patients with cancer, particularly when the goal of treatment is cure. There is no evidence that short- or long-term toxicity is increased among obese patients receiving full weight-based doses. Most data indicate that myelosuppression is the same or less pronounced among the obese than the non-obese who are administered full weight-based doses. Clinicians should respond to all treatment-related toxicities in obese patients in the same ways they do for non-obese patients. The use of fixed-dose chemotherapy is rarely justified, but the Panel does recommend fixed dosing for a few select agents. The Panel recommends further research into the role of pharmacokinetics and pharmacogenetics to guide appropriate dosing of obese patients with cancer.

Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline

PURPOSE To provide evidence-based recommendations to oncologists and others for treatment of patients with locally advanced, unresectable pancreatic cancer. METHODS American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts and conducted a systematic review of the literature from January 2002 to June 2015. Outcomes included overall survival, disease-free survival, progression-free survival, and adverse events. RESULTS Twenty-six randomized controlled trials met the systematic review criteria. RECOMMENDATIONS A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. The goals of care, patient preferences, psychological status, support systems, and symptoms should guide decisions for treatments. A palliative care referral should occur at first visit. Initial systemic chemotherapy (6 months) with a combination regimen is recommended for most patients (for some patients radiation therapy may be offered up front) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile. There is no clear evidence to support one regimen over another. The gemcitabine-based combinations and treatments recommended in the metastatic setting (eg, fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound paclitaxel) have not been evaluated in randomized controlled trials involving locally advanced, unresectable pancreatic cancer. If there is local disease progression after induction chemotherapy, without metastasis, then radiation therapy or stereotactic body radiotherapy may be offered also with an Eastern Cooperative Oncology Group performance status ≤ 2 and an adequate comorbidity profile. If there is stable disease after 6 months of induction chemotherapy but unacceptable toxicities, radiation therapy may be offered as an alternative. Patients with disease progression should be offered treatment per the ASCO Metastatic Pancreatic Cancer Treatment Guideline. Follow-up visits every 3 to 4 months are recommended. Additional information is available at www.asco.org/guidelines/LAPC and www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki.

The frequency of anemia and iron deficiency in the runner

The current consensus is that runners commonly experience a mild anemia influenced by iron deficiency. We compared hematologic parameters of 72 (35 males and 37 females) runners with 48 (27 males and 21 females) nonrunners and assessed the impact of iron supplementation. Male runners had lower hemoglobin (Hb) values than male nonrunners (14.8 vs 15.3 g.dl-1) (P less than 0.05) regardless of iron usage. Female runners had higher (P = 0.05) Hb values than female controls (13.5 vs 12.8 g.dl-1). Female runners off iron had Hbs similar to controls off iron (P = 0.30). Iron parameters (total serum iron, TSI; total iron-binding capacity, TIBC; percent saturation of the TIBC, %sat TIBC; and serum ferritin) of runners vs controls, runners vs runners (on or off iron), and nonrunners vs nonrunners (on or off iron) were comparable except 1) male runners off iron had lower (P less than 0.05) %sat TIBC values (26%) than male runners on iron (34%) and 2) female runners taking iron had ferritin values (32 ng.ml-1) similar to those of female nonrunners taking iron (39 ng.ml-1) but higher (P less than 0.05) than their counterparts off iron (15 and 15 ng.ml-1, respectively). This study concludes that running affects Hb in a variable manner and suggests that the runners iron status is similar to that of the general population.

Treatment of Cutaneous Sclerosis and Aplastic Anemia with Antithymocyte Globulin

We administered antithymocyte globulin to a 52-year-old man with cutaneous sclerosis (scleroderma) and severe aplastic anemia for treatment of the aplastic lesion. The use of this therapy resulted not only in marrow recovery but also in resolution of the sclerosis. This observation indicates that T lymphocytes, their products, or both, are important factors in the pathogenesis of cutaneous sclerosis. Furthermore, the success of this treatment could play a role in future investigations involving the treatment of scleroderma and scleroderma-like conditions.

The impact of dose intensity of standard chemotherapy regimens in extensive stage small cell lung cancer

Oncologists often attenuate the doses of chemotherapy drugs in published standard regimens to avoid toxicity. The impact on survival of this practice in patients with extensive stage small cell lung cancer (SCLC) is uncertain. We have compared the outcome of 85 patients treated with a program of cyclophosphamide, doxorubicin, and vincristine to a group of 37 patients treated with conventional regimens of higher dose intensity. The two groups of patients were shown to be equivalent in terms of staging evaluation, response and survival criteria, and pretreatment prognostic factors. The latter was confirmed by applying a published prognostic algorithm. Complete response rates (38% vs 14%) were significantly better with the higher intensity regimens (p = .003). The median survival (39 vs 26 weeks), 1 year survival (32% vs 12%), and overall survival (p = .002) were superior with the full-dose intensity protocols. Myelotoxicity was also greater with the contemporary treatments. Cox proportional hazards analysis, correcting for pretreatment prognostic variables, confirmed the improved survival with conventional doses of therapy (p = .0055). These results support the concept that full-dose intensity chemotherapy provides survival benefit in patients with extensive stage SCLC.

The relative value of conventional staging procedures for developing prognostic models in extensive-stage small-cell lung cancer.

Published prognostic models for small-cell lung cancer (SCLC) have either combined limited- and extensive-stage patients or have not included standard anatomic staging information to assess the relative value of the knowledge of specific sites and number of sites of metastases in predicting survival in extensive-stage disease. We studied 136 extensive-stage patients in whom traditional staging procedures were performed and in whom other previously demonstrated significant pretreatment variables were determined. Using the Cox proportional hazards model, when all data were included, three variables were significant: performance status (PS) (P = .0001), number of sites of metastases (P = .0010), and age (P = .0029). A prognostic algorithm was developed using these variables, which divided the patients into three distinct groups. When the anatomic staging data were omitted, the serum albumin (P = .0313) was the only variable in addition to PS (P = .0001) and age (P = .0064) that was significant. An alternative algorithm using these three variables was nearly as predictive as the original. Therefore, in extensive-stage patients, reasonable pretreatment prognostic information can be obtained without using the number or specific sites of metastases as variables once the presence of distant metastases has been demonstrated.

Radionuclide imaging of bone marrow metastases with a Tc-99m labeled monoclonal antibody to small cell lung carcinoma

The detection of metastatic disease confined to the bone marrow compartment has in the past been technically limited. We have identified excellent imaging of bone marrow metastases during the evaluation of a Tc-99m labeled monoclonal antibody (NR-LU-10 Fab) (NeoRx Corp., Seattle, WA). This occurred during a study to assess the monoclonal antibodys ability to detect sites of small cell cancer (primary and metastatic). The study by design compares areas seen by the monoclonal antibody scan with those found by standard staging methods in patients with small cell lung cancer. Standard staging included chest x-rays, bone scans, CT studies of the abdomen, and histologic examination of the bone marrow. Fifteen patients have been evaluated, four on two occasions, for a total of 19 monoclonal imaging studies. Metastasis to the marrow compartment was identified by the monoclonal imaging in all patients whose bone marrow biopsies were positive for small cell carcinoma, and it was primarily responsible for the eventual detection of extensive disease (marrow involvement) in one patient. Thus it appears that compartmental bone marrow imaging for metastatic disease is possible with immunoscintigraphy.

Double modulation of 5-fluorouracil in the treatment of advanced colorectal carcinoma: report of a trial with sequential methotrexate, intravenous (loading dose) folinic acid, 5-fluorouracil, and a literature review.

5-Fluorouracil (5-FU) modulation with either folinic acid (FA) or methotrexate (MTX) has improved 5-FUs potential cytoreductivity. We combined MTX and FA with 5-FU to further augment 5-FUs cytoreductivity. Patients (n = 34) with advanced colorectal carcinoma were first given intravenous MTX (escalated from 30 mg/m2 to 70 mg/m2). FA (100 mg/m2) was infused 17-24 hr later, followed by 5-FU (600 mg/m2). Oral rescue doses of FA were begun 24 hr after MTX. Patients were treated every 2 weeks. No previously treated patient (n = 6) responded. Eight of the remaining 28 (29%) (95% confidence interval, 15-47%) patients achieved a PR. Median survival was 9.3 months. Toxicity (primarily gastrointestinal) necessitated dosage modification in 10 patients (29%). These results, in addition to a literature review, reveal that the manipulation of 5-FU by two modulating agents does not improve the response rate seen with single-agent modulation.