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

Exercise for the treatment of lymphedema — The potential benefits of upper extremity exercise on secondary lymphedema in breast cancer patients were illustrated in a randomized controlled trial of supervised weight lifting [1]. (See "Lymphedema: Prevention and treatment", section on 'Treatment'.)

CHEMOTHERAPEUTIC AGENTS

Cetuximab and panitumumab labeling revised for K-ras mutations — The United States Food and Drug Administration (USFDA) has approved revisions to the prescribing information for cetuximab and panitumumab, indicating that the use of these drugs is not recommended for treatment of advanced colorectal cancer in patients whose tumors have a K-ras mutation in codon 12 or 13. (See "Systemic chemotherapy for metastatic colorectal cancer: Completed clinical trials", section on 'Molecular determinants of response'.)

Cetuximab and hypokalemia — In a meta-analysis of 11 clinical reports, nearly one out of every ten patients receiving cetuximab for treatment of advanced cancer developed hypokalemia, often severe, during therapy [2]. Periodic monitoring of serum potassium levels is warranted in patients receiving cetuximab. (See "Chemotherapy and renal insufficiency", section on 'EGFR pathway inhibitors'.)

Bevacizumab and risk of CNS hemorrhage in patients with brain metastases — Bevacizumab is increasingly used in patients with advanced breast and non-small cell lung cancer, in whom brain metastases are common. Given that bleeding is a known complication of bevacizumab therapy, concerns have been raised as to the risk of central nervous system (CNS) hemorrhage in patients who have nonhemorrhagic brain metastases. In a prospective study of 115 patients with brain metastases who were treated with a bevacizumab-containing regimen for advanced non-small cell lung cancer (NSCLC), there were no CNS hemorrhages [3]. Thus, patients with treated nonhemorrhagic brain metastases need not be excluded from systemic therapy with bevacizumab. (See "Systemic chemotherapy for brain metastases", section on 'Risk of CNS hemorrhage with bevacizumab'.)

GASTROINTESTINAL CANCER

Aspirin improves survival in patients with resected colon cancer — A substantial body of evidence supports a protective effect of aspirin and other NSAIDs on the development of colonic adenomas and cancers. New data suggest that aspirin may also influence the biology of established colon cancers. In an observational study of patients receiving adjuvant treatment for nonmetastatic colon cancer, aspirin users had a significant 29 percent lower cancer-specific mortality and a 21 percent lower overall mortality compared to nonusers [4]. Benefit was limited to those whose resected tumors overexpressed COX-2. Prospective confirmation of the benefit of aspirin in a randomized trial is needed before routine use of aspirin can be recommended, given the potential for harm (eg, gastrointestinal bleeding). (See "Adjuvant therapy for resected colon cancer", section on 'Aspirin'.)

Vistonuridine and 5-FU overdose — Vistonuridine is an orally administered prodrug of uridine, a specific pharmacologic antidote to 5-fluorouracil (5-FU). It is a safe, effective, and potentially life-saving treatment for 5-FU overdose. In a preliminary study, recovery was reported in all 17 cases treated with vistonuridine for 5-FU overexposure, compared to 2 of 13 who did not receive it [5]. (See "Enterotoxicity of chemotherapeutic agents", section on 'Predictive markers'.)

Vistonuridine is not commercially available, but it has received orphan drug designation for treatment of 5-FU overexposure from both the United States Food and Drug Administration (USFDA) and the European Medicines Agency. In the US, it is available from its manufacturer, Wellstat Therapeutics, under an emergency-use Investigational New Drug (IND) waiver.

Adjuvant chemotherapy for pancreatic cancer — The multicenter randomized ESPAC3 trial directly compared six months of adjuvant treatment with either gemcitabine or bolus leucovorin-modulated 5-FU in patients with resected pancreatic ductal adenocarcinoma [6]. In a preliminary report, the median survival was similar in both groups; however, patients assigned to 5-FU/leucovorin had more grade 3 to 4 treatment-related toxicity and more treatment-related hospitalizations. Given this safety profile, gemcitabine is the preferred agent. (See "Adjuvant and neoadjuvant therapy for pancreatic adenocarcinoma", section on 'Gemcitabine versus 5-FU'.)

Lack of benefit for irinotecan after complete resection of colorectal cancer liver metastases — A course of systemic chemotherapy is usually recommended following resection of isolated colorectal cancer liver metastases, although whether this practice increases cure rates remains unproven. A phase III trial demonstrated no benefit from the addition of irinotecan to 5-FU and leucovorin-based chemotherapy after resection of isolated colorectal cancer liver metastases [7]. Thus, postoperative administration of irinotecan-containing chemotherapy should not be considered a standard approach following resection of liver-isolated metastatic colorectal cancer. (See "Management of potentially resectable colorectal cancer liver metastases", section on 'Systemic chemotherapy'.)

Intermittent versus continuous chemotherapy in patients receiving oxaliplatin for metastatic colorectal cancer — For patients receiving oxaliplatin-based regimens (eg, FOLFOX) for treatment of metastatic colorectal cancer, dose-limiting sensory neuropathy can by mitigated by intermittent oxaliplatin-free intervals. Results from the OPTIMOX2 trial suggest that patients may have a worse outcome if courses of oxaliplatin-based chemotherapy are interspersed with entirely chemotherapy-free intervals [8]. Thus, for patients who develop neuropathy while receiving an oxaliplatin-based regimen (or who have received a cumulative oxaliplatin-dose of ≥680 mg/m2), it is reasonable to discontinue oxaliplatin temporarily while maintaining infusional 5-FU and leucovorin. (See "Systemic chemotherapy for metastatic colorectal cancer: Completed clinical trials", section on 'Intermittent versus continuous oxaliplatin'.)

GENERAL ONCOLOGIC ISSUES

Ginger to prevent chemotherapy-induced nausea — Conventional antiemetics are less effective for the prevention of chemotherapy-induced nausea compared to prevention of vomiting. A randomized placebo-controlled trial conducted in patients receiving a variety of chemotherapy regimens concluded that the addition of ginger (0.5 or 1 g twice daily for six days, starting three days prior to the first day of each chemotherapy cycle) to conventional antiemetics significantly aids in reduction of day 1 nausea [9]. (See "Prevention and treatment of chemotherapy-induced nausea and vomiting", section on Ginger and nonpharmacologic therapies.)

GENITOURINARY CANCER

Bevacizumab approved for renal cell carcinoma — Bevacizumab was approved by the United States FDA for use in combination with interferon alfa for the treatment of patients with metastatic renal cell carcinoma [10]. The approval was based upon two phase III trials that compared bevacizumab plus interferon to interferon alone [11,12]. (See "Molecularly targeted therapy for advanced renal cell carcinoma", section on 'Bevacizumab'.)

Adjuvant chemotherapy for urothelial carcinoma — Two major studies failed to demonstrate a survival benefit from adjuvant chemotherapy in patients with urothelial cancer.

• In a randomized trial presented at the 2009 ASCO meeting, there were no differences in time to recurrence or overall survival in 114 patients with p53 positive tumors who were randomized to observation or adjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) following cystectomy [13]. (See "Adjuvant chemotherapy for urothelial (transitional cell) carcinoma of the bladder", section on 'Randomized trials'.)

• In a retrospective study of 1390 patients who underwent nephrouterectomy for urothelial cancer of the ureter or renal pelvis, adjuvant therapy did not improve survival compared to observation [14]. (See "Neoplasms of the renal pelvis and ureter", section on 'Adjuvant chemotherapy'.)

GYNECOLOGIC ONCOLOGY

Dose-dense paclitaxel for first-line chemotherapy of epithelial ovarian cancer — The optimal schedule and dose of paclitaxel when used in combination with carboplatin for treatment of advanced epithelial ovarian cancer (EOC) is uncertain. A Japanese trial of weekly ("dose dense") versus every three week paclitaxel in combination with every three week carboplatin in women receiving first-line therapy for EOC concluded that dose-dense therapy was associated with a statistically significant improvement in both progression-free and overall survival [15]. However, these benefits were achieved at the cost of more pronounced treatment-related toxicity in the dose-dense arm. Thus, this approach is not necessarily favored over every three week paclitaxel in conjunction with carboplatin. (See "First-line chemotherapy for epithelial ovarian cancer", section on Dose, schedule, and duration of paclitaxel infusion.)

Posttreatment surveillance for cervical cancer — An analysis of the available evidence by the Cancer Care Ontario's Program in Evidence-based Care concluded that there was at best only modest low-quality evidence to inform the most appropriate follow-up strategy for patients who are disease-free after receiving primary treatment for cervical cancer [16]. Only 6 percent of asymptomatic recurrences were diagnosed based upon vaginal vault cytology, leading this group to recommend that cytology be obtained no more than once yearly. (See "Invasive cervical cancer: Patterns of recurrence and posttreatment surveillance".)

MELANOMA AND SKIN CANCER

Adjuvant radiation therapy does not improve melanoma survival — In a report of a phase III trial presented at the 2009 ASCO meeting, adjuvant radiation therapy did NOT improve overall survival in patients with melanoma and positive regional lymph nodes [17]. (See "Role of radiation therapy in the management of melanoma", section on 'Adjuvant RT'.)

Targeted therapy for metastatic melanoma — Two studies presented at the 2009 ASCO meeting reported clinically significant responses using molecularly targeted agents in patients with metastatic melanoma and specific mutations:

• An inhibitor of the BRAF oncogene (PLX4032) induced a partial response in 9 of 16 patients (56 percent) with metastatic melanoma and activating mutations of this gene [18].
• Imatinib induced two complete and two partial responses in 12 patients with activating mutations in the c-kit oncogene [4].

Expanded studies with each of these agents in patients selected based upon the molecular characteristics of their tumor are in progress. (See "Cytotoxic chemotherapy and biochemotherapy for metastatic melanoma", section on 'Novel approaches'.)

Targeted therapy in metastatic basal cell carcinoma — In a phase I study in 33 patients with metastatic or locally advanced basal cell carcinoma, targeted inhibition of the hedgehog pathway induced objective responses in more than one-half of patients [19]. (See "Systemic treatment of advanced cutaneous squamous and basal cell carcinomas", section on 'Hedgehog signaling pathway'.)

NON-SMALL CELL LUNG CANCER (NSCLC)

Revised TNM staging system — A major revision of the tumor node metastasis (TNM) staging system was approved by the International Association for the Study of Lung Cancer (IASLC) in August 2009 [20]. The seventh edition of the TNM system and changes from the sixth edition are shown in Tables 1 and 2 (table 1 and table 2). (See "TNM staging system for non-small cell lung cancer".)

Sequential non-cross resistant therapy for advanced NSCLC — Two phase III trials provided evidence that sequential non-cross-resistant therapy improves progression-free survival and may improve overall survival in patients with metastatic NSCLC who responded to an initial chemotherapy regimen:

Pemetrexed approved for maintenance therapy — The United States FDA approved pemetrexed for maintenance treatment of patients with locally advanced or metastatic nonsquamous NSCLC [21]. The approval was based upon a trial in which maintenance therapy with pemetrexed significantly increased both progression-free and overall survival [22]. (See "Sequential non-cross-resistant therapy for patients responding to initial treatment of advanced non-small cell lung cancer", section on 'Contemporary regimens'.)

Erlotinib — In a phase III trial, erlotinib significantly prolonged progression-free survival (PFS) compared to placebo after initial chemotherapy in patients with metastatic NSCLC [23]. (See "Sequential non-cross-resistant therapy for patients responding to initial treatment of advanced non-small cell lung cancer", section on 'EGFR TK inhibitors'.)

Gefitinib approved for initial therapy of metastatic NSCLC — The European Medicines Agency (EMEA) approved gefitinib for the initial treatment of patients with metastatic NSCLC who have activating mutations of the epidermal growth factor receptor (EGFR) tyrosine kinase (TK) [24]. In the phase III IPASS trial, the EGFR TK inhibitor gefitinib was more effective than carboplatin plus paclitaxel in previously untreated patients who were enrolled based upon an increased likelihood of response (adenocarcinoma, never or former light smokers) [25]. (See "Targeted agents in the initial systemic treatment of advanced non-small cell lung cancer", section on 'EGFR TK inhibitors'.)

Long-term results of adjuvant chemotherapy — Results of the JBR 10 adjuvant chemotherapy trial were updated at the 2009 ASCO meeting at a median follow-up of over nine years [26]. There was a continuing survival advantage for patients with stage II disease. Although adjuvant therapy improved survival for patients with stage I disease and a primary tumor >4 cm, survival was longer with observation for those with a primary tumor <4 cm. (See "Adjuvant systemic therapy in resectable non-small cell lung cancer", section on 'JBR 10'.)

Prophylactic cranial irradiation — In a phase III RTOG trial presented at the 2009 ASCO meeting, prophylactic cranial irradiation in patients with stage III NSCLC significantly decreased the incidence of brain metastases but did NOT prolong survival [27]. (See "Management of stage III non-small cell lung cancer", section on 'Prophylactic cranial irradiation'.)

EML4-ALK fusion oncogene — The presence of the EML4-ALK fusion oncogene identifies a subset of patients with metastatic NSCLC who respond to targeted therapy. In results presented at the 2009 ASCO meeting, a specific inhibitor of this target (PF-02341066) induced responses in over 50 percent of patients carrying this fusion oncogene [28]. (See "Molecular markers in non-small cell lung cancer", section on 'EML4-ALK fusion gene'.)

PROSTATE CANCER

Denosumab to prevent bone loss from androgen deprivation therapy — In a phase III trial in men treated with androgen deprivation therapy (ADT) for advanced prostate cancer without bone metastases, denosumab, a monoclonal antibody that binds RANKL, significantly decreased the incidence of new vertebral fractures [29]. (See "Managing the side effects of androgen deprivation therapy", section on 'Denosumab'.)

Increased mortality after neoadjuvant ADT in men with heart disease — There was a significant increase in all-cause mortality in men with preexisting heart failure or a history of myocardial infarction who received neoadjuvant ADT prior to brachytherapy for localized, node negative prostate cancer [30]. (See "Managing the side effects of androgen deprivation therapy", section on 'Cardiovascular disease' and "Brachytherapy for localized prostate cancer", section on 'Prostate gland size'.)

Active surveillance — In the Health Professionals Follow-up Study one-half of men with localized prostate cancer who were not treated during the first year after diagnosis remained untreated at a median follow-up of seven years [31]. Multivariate analysis incorporating stage of disease, Gleason score, and serum PSA found no significant difference in the risk of developing metastases or dying of prostate cancer for men with localized prostate cancer observed for at least one year compared to those receiving immediate treatment. (See "Active surveillance for men with early prostate cancer", section on 'Observational studies'.)