INTRODUCTION — The following represent additions to UpToDate since the last version that were considered by the authors and editors to be of particular interest. The new material described below represents a small subset of the updating that has been performed, since approximately 40 percent of the topic reviews are updated during each four-month cycle.

BREAST CANCER

Breast cancer prevention with raloxifene and tamoxifene — An update of the Study of Tamoxifen and Raloxifene (STAR trial), which randomly assigned postmenopausal women at increased risk of breast cancer to raloxifene or tamoxifen, was presented at the 2010 American Association for Cancer Research Meeting [1]. After 81 months of follow-up, raloxifene was significantly less effective than tamoxifen in reducing the risk of invasive breast cancer, but raloxifene maintained its toxicity advantage. Women who received raloxifene had significantly fewer uterine cancers, hysterectomies for benign disease, and thromboembolic events. (See "Selective estrogen receptor modulators for the prevention of breast cancer", section on 'STAR trial'.)

MRI in the diagnosis of breast cancer — A randomized trial in women with biopsy-prove primary breast cancer scheduled for wide local excision found that the addition of magnetic resonance imaging (MRI) to standard clinical, radiologic, and pathologic preoperative assessment of the affected breast failed to reduce reoperation rates compared to conventional assessment alone [2]. (See "Diagnostic evaluation of women with suspected breast cancer", section on 'Breast MRI'.)

CHEMOTHERAPEUTIC AGENTS

Risk assessment, monitoring, and management of hypertension in patients receiving angiogenesis inhibitors — Guidelines for risk assessment, early recognition, and management of hypertension in patients treated with vascular endothelial growth factor (VEGF) signaling pathway inhibitors (eg, bevacizumab, sunitinib, sorafenib) are available [3]. The recommendations include pretreatment risk assessment for potential cardiovascular complications, management of preexisting hypertension before initiating therapy, active monitoring of blood pressure during treatment, particularly in the first several weeks, and aggressive management of blood pressure during therapy, using prespecified goals. (See "Overview of angiogenesis inhibitors", section on 'Hypertension'.)

Preemptive oral antibiotics in patients receiving anti-EGFR targeted therapy — Up to two-thirds of patients treated with the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab and panitumumab develop a diffuse acneiform skin rash. Modest benefit from prophylactic oral antibiotics was suggested in a randomized trial that compared preemptive therapy (doxycycline 100 mg twice daily during therapy, a daily application of 1 percent hydrocortisone cream, topical emollients, and sunscreen use) versus symptomatic treatment in 95 patients receiving panitumumab for metastatic colorectal cancer [4]. At six weeks, grade 2 or worse skin toxicity occurred in significantly fewer subjects in the prophylactic group, and preemptive treatment did not adversely affect treatment response. (See "Cutaneous complications of molecularly targeted therapy and other biologic agents used for cancer therapy", section on 'Prophylactic therapy'.)

Pazopanib-induced hyperbilirubinemia — Pazopanib, an oral multitargeted tyrosine kinase agent inhibitor, causes transaminase elevation and/or hyperbilirubinemia in approximately 18 percent of patients. The United States Food and Drug Association (FDA)-approved package labeling recommends that treatment be interrupted or discontinued in the event of hepatotoxicity.

Some cases of isolated pazopanib-induced hyperbilirubinemia are associated with inheritance of polymorphisms in the uridine diphosphoglucuronosyltransferase 1A1 (UGT 1A1) enzyme that cause Gilbert's syndrome (the*28 allele) [5]. This raises the possibility that isolated hyperbilirubinemia might represent a benign manifestation of Gilbert's syndrome rather than pazopanib toxicity and that drug continuation might be reasonable in this setting. Genetic testing for the UGT 1A1*28 allele is available (the Invader UGT1A1 Molecular Assay). (See "Chemotherapy hepatotoxicity and dose modification in patients with liver disease".)

Neuroprotection with vitamin E in patients receiving cisplatin — A possible neuroprotective effect of vitamin E in patients receiving high cumulative doses of cisplatin was suggested in a small placebo-controlled randomized trial [6]. In an analysis limited to 41 patients (17 vitamin E and 24 placebo) who received at least 300 mg/m2 of cisplatin, those who received vitamin E (400 units daily) during and for three months following treatment discontinuation had significantly lower total cumulative neuropathy scores and a significantly lower incidence of grade 3 neurotoxicity (6 versus 42 percent). (See "Neurologic complications of platinum-based chemotherapy", section on 'Preventive strategies'.)

GASTROINTESTINAL CANCER

Superiority of FOLFIRINOX over gemcitabine as initial therapy for metastatic pancreatic cancer — The superiority of short-term infusional 5-FU, leucovorin, oxaliplatin plus irinotecan (FOLFIRINOX) over gemcitabine monotherapy was shown in a randomized phase III trial conducted in 250 patients with previously untreated metastatic pancreatic cancer, a good performance status, and serum bilirubin level less than 1.5 times the upper limit of normal (ULN) [7]. In a preliminary report presented at the 2010 ASCO meeting, FOLFIRINOX was associated with significantly higher objective response rates (31 versus 9 percent), median progression-free survival, and overall survival (11.1 versus 6.8 months). However, these benefits were achieved at the cost of significantly more toxicity (including severe neutropenia, febrile neutropenia, thrombocytopenia, neuropathy, vomiting, diarrhea, and fatigue). These results establish FOLFIRINOX as the preferred initial chemotherapy regimen in patients with metastatic pancreatic cancer who have a good performance status and a serum total bilirubin level less than 1.5 times the ULN. (See "Chemotherapy for advanced exocrine pancreatic cancer", section on 'FOLFIRINOX'.)

Gemcitabine plus cisplatin for advanced biliary tract cancer — The superiority of weekly gemcitabine plus cisplatin over gemcitabine alone for treatment of advanced cholangiocarcinoma, gallbladder cancer, and ampullary cancer was shown in the multicenter ABC-02 trial [8]. Both median and progression-free survival were significantly greater with combination therapy, and this improvement did not come at a cost of greater treatment-related toxicity. Gemcitabine plus cisplatin could be considered a standard regimen for treatment of advanced biliary tract cancer. (See "Systemic therapy for advanced cholangiocarcinoma", section on 'Gemcitabine plus cisplatin'.)

GENERAL ONCOLOGIC ISSUES

Extended release hydromorphone — An extended release form of hydromorphone is now available in the US (Exalgo®) for use in opioid tolerant patients [9]. It is available in 8, 12, and 16 mg strengths, and is dosed once daily. Caution must be used to avoid medication errors when prescribing this product, as 8 mg tablets are also available as immediate-release hydromorphone tablets. (See "Cancer pain management with opioids: Optimizing analgesia".)

GENITOURINARY CANCER

Fluorescence endoscopy for bladder cancer — The United States Food and Drug Administration approved the use of 5-aminolevulinic acid (ALA) for use in conjunction with cystoscopy for the diagnosis of non-muscle invasive bladder cancer. The approval was based upon randomized trials showing that this approach can increase the sensitivity of cystoscopy compared to conventional white light cystoscopy [10]. (See "Treatment of non-muscle-invasive bladder cancer", section on 'Fluorescence endoscopy'.)

GYNECOLOGIC ONCOLOGY

First-line bevacizumab in epithelial ovarian cancer — Preliminary results of the Gynecologic Oncology Group (GOG) trial 218 presented at the 2010 meeting of the American Society of Clinical Oncology found that the addition of concurrent bevacizumab to six courses of first-line paclitaxel plus carboplatin followed by up to 11 months of maintenance bevacizumab significantly increased progression-free survival as compared to IV paclitaxel plus carboplatin alone in women with surgically cytoreduced stage III or IV epithelial ovarian, primary peritoneal, or fallopian tube cancer [11]. Benefit could not be shown for paclitaxel and carboplatin plus concurrent in the absence of maintenance bevacizumab.

Incorporation of bevacizumab into first-line chemotherapy could be considered an option for women with epithelial ovarian, primary peritoneal, or fallopian tube cancer who are candidates for bevacizumab. However, whether a bevacizumab-containing regimen should be considered the standard of care awaits maturation of these and other trial data. (See "First-line chemotherapy for epithelial ovarian cancer", section on 'Benefit of bevacizumab'.)

Adjuvant radiotherapy for endometrial cancer — The randomized PORTEC-2 trial demonstrated that postoperative adjuvant vaginal brachytherapy was as effective for locoregional control as pelvic external beam RT in women with high-intermediate-risk endometrial cancer, with fewer gastrointestinal side effects [12]. (See "Endometrial cancer: Postsurgical adjuvant therapy, primary radiotherapy for nonsurgical candidates, and prognosis", section on 'Adjuvant RT'.)

Serum assay for HE4 approved for detection of recurrent ovarian cancer — An assay to detect elevated serum levels of the Human Epididymus Protein antigen HE4 (the Architect HE4 Test) was approved by the United States Food and Drug Administration for monitoring patients with epithelial ovarian cancer for disease recurrence or progression. (See "First-line chemotherapy for epithelial ovarian cancer", section on 'Posttreatment surveillance'.)

HEAD AND NECK CANCER

Cetuximab concurrent with radiation therapy for locoregionally advanced head and neck cancer — In an update of a multinational randomized trial of patients with locoregionally advanced head and neck cancer, concurrent cetuximab with radiation therapy (RT) continues to show significantly increased five-year overall survival compared to RT alone [13]. An underpowered subset analysis showed that the benefit of cetuximab concurrent with RT was restricted to patients UNDER the age of 65 years and with an excellent Karnofsky performance score. However, its effectiveness in patients over the age of 65 or with comorbidities or a poor performance status was not confirmed. (See "Concurrent chemoradiation for locoregionally advanced head and neck cancer", section on 'Molecularly targeted agents'.)

MELANOMA

Ipilimumab improves survival in metastatic melanoma — The CTLA4 receptor on T lymphocytes can block positive stimulatory signals mediated by other T cells. Ipilimumab binds to that receptor, thus potentiating the immune response. In a phase III trial, induction therapy with ipilimumab significantly improved overall survival in patients with unresectable metastatic melanoma [14]. (See "Experimental immunotherapy for melanoma", section on 'Ipilimumab'.)

NEUROONCOLOGY

TP53 mutations in medulloblastoma — Mutations in the TP53 gene are associated with early relapse and death in patients with medulloblastoma, even when other factors would indicate that the prognosis is relatively favorable [15]. (See "Epidemiology, treatment, and prognosis of medulloblastoma", section on 'Molecular markers'.)

NON-SMALL CELL LUNG CANCER (NSCLC)

Maintenance erlotinib in patients with metastatic non-small cell lung cancer — The United States Food and Drug Administration approved the use of erlotinib as maintenance therapy in patients who do not have progressive disease after four cycles of chemotherapy for metastatic non-small cell lung cancer (NSCLC). The approval was based upon the results of the SATURN trial, which demonstrated an increase in both progression-free and overall survival [16]. (See "Sequential non-cross-resistant therapy for patients responding to initial treatment of advanced non-small cell lung cancer", section on 'EGFR TK inhibitors'.)

PROSTATE CANCER

Sipuleucel-T (Provenge) approval — The US Food and Drug Administration approved the therapeutic dendritic cell vaccine sipuleucel-T in April 2010 for the treatment of asymptomatic or minimally symptomatic men with castrate-resistant metastatic prostate cancer. Approval was based upon the results of three randomized trials that demonstrated an improvement of four months in overall survival compared to placebo [17,18]. (See "Immunotherapy for metastatic prostate cancer", section on 'Sipuleucel-T'.)

Cabazitaxel for metastatic prostate cancer — In preliminary results from a phase III trial, the combination of the taxane derivative cabazitaxel plus prednisone significantly increased survival compared to mitoxantrone plus prednisone in men with metastatic prostate cancer that had progressed on docetaxel [19]. Cabazitaxel was approved by the US Food and Drug Administration June 17, 2010 for use in combination with prednisone for men previously treated with docetaxel. (See "Chemotherapy in castrate-resistant prostate cancer", section on Capazitaxel.)

Dutasteride for prostate cancer chemoprevention — The REDUCE randomized trial evaluated the role of dutasteride, a 5 alpha reductase inhibitor, as prophylaxis for prostate cancer in men at increased risk based upon age and serum PSA level [20]. Dutasteride, compared to placebo, reduced the incidence of low Gleason score prostate cancer. The decision of whether or not to use a 5-alpha reductase inhibitor requires an informed decision balancing the risks and potential benefits. (See "Chemoprevention strategies in prostate cancer", section on '5-Alpha reductase inhibitors'.)

RADIATION THERAPY

Cardiovascular mortality in survivors of pediatric cancer — Two large, retrospective studies found that long-term follow-up of pediatric cancer survivors who had been treated with radiation therapy had an increased risk of cardiac and cardiovascular mortality [21,22]. (See "Cardiotoxicity of radiation therapy for malignancy", section on 'Pediatric patients'.)

SOFT TISSUE AND BONE TUMORS

Denosumab for giant cell tumor of bone — Denosumab is a fully human monoclonal antibody against the receptor activator of nuclear factor kappa B ligand (RANKL), a molecule that is critical to the pathogenesis of giant cell tumor of bone (GCTB). The benefit of targeting RANKL as a therapeutic strategy in GCTB was shown in a phase II study of subcutaneous denosumab in 37 patients with recurrent or unresectable GCTB, in which 30 (86 percent) had an objective response to therapy [23]. While denosumab is not yet approved as a treatment for GCTB, it is approved in the United States as a treatment for osteoporosis in postmenopausal women. (See "Giant cell tumor of bone", section on 'RANKL inhibitors: Denosumab'.)

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