Lisa Richards

Hepatectomy-induced metastasis.

volume 7 | sePtemBer 2010 | 482 Darbepoetin-alpha, an agent for improving liver regeneration after hepatectomy, has been reported to cause a substantial increase in hepatectomy-induced stimulation of colorectal liver metastatic growth. Data from a mouse study suggest that erythropoiesis-stimulating agents are not suitable for patients in whom hepatectomy is performed for malignant tumor resection. Liver resection is the gold standard treatment of colorectal liver metastases; however, liver insufficiency is a serious complication after major hepatectomy. Erythropoietin and its analog darbepoetin-alpha are suitable agents to improve liver function after resection, owing to their cytoprotective, antiapoptotic and anti-inflammatory effects. Despite this promise, reports on the effect of erythropoietin on overall survival in cancer patients vary and the agent may promote tumor progression. Rupertus and colleagues evaluated the effect of darbepoetin-alpha on hepatic tumor growth in a mouse model of colorectal cancer. The growth of liver metastases was notably greater in mice that underwent 50% hepatectomy in comparison with unresected mice. Furthermore, hepatectomized mice treated with darbepoetin-alpha displayed dramatically enhanced hepatectomyinduced stimulation of colorectal liver metastatic growth. Treatment with darbepoetin-alpha alone had only a slight effect on metastatic growth. The researchers associated this enhanced growth with increased neovascularization—a mechanism observed in the mice treated with hepatectomy alone but augmented by the addition of darbepoetin-alpha— reduction of tumor cell apoptosis and inhibition of leukocyte adhesion. In conclusion, erythropoietin-stimulating agents might be best avoided in patients undergoing hepatectomy.

Targeted therapies: disappointing outcomes for anti-VEGF therapy.

In a randomized, double-blind, phase III study, Hedy Kindler and co-workers investigated the effect of adding axitinib to gemcitabine for the treatment of advanced pancreatic cancer. “Axitinib is a potent and selective inhibitor of VEGF receptors 1, 2, and 3 that has demonstrated clinical efficacy in multiple solid tumors,” Kindler describes. No significant difference in overall survival was observed between patients receiving gemcitabine alone or in combination with axitinib (8.3 months versus 8.5 months). “These data do not support results from the earlier phase II study suggesting that axitinib may improve survival when combined with gemcitabine in this setting,” comments Kindler. The data do, however, support findings from other studies of bevacizumab and aflibercept suggesting that inhibition of the VEGF pathway is ineffective in patients with pancreatic cancer. “The results highlight the importance of conducting phase III evaluation only after detection of a robust TARGETED THERAPIES

Epidemiology: Human papillomavirus|[mdash]|a powerful predictor of survival in patients with oropharyngeal cancer

Epidemiology: Human papillomavirus—a powerful predictor of survival in patients with oropharyngeal cancer

Genetics: Staging and prognostic value of p16 expression in oropharyngeal cancer.

a strong independent prognostic marker for oropharyngeal squamous cell carcinoma (oPsCC) has been identified by researchers in switzerland. the report suggests that expression of p16 should be included in the official staging system for head and neck squamous cell carcinoma (HnsCC) to identify patients with oPsCC. Claude Fischer and colleagues found that p16 was a stronger and more reliable prognostic factor than conventional staging parameters. Currently, primary tumor extension, lymph-node involvement and distant metastasis are used to determine the stage of HnsCC. a step towards improved differentiation of HnsCC into distinct subgroups was achieved by the identification of human papillomavirus 16 and 18 in a subset of oPsCCs, which has a distinctive p16 expression profile. Fischer et al. retrospectively evaluated the prognostic value of p16 expression relative to the established prognostic markers in 102 patients with oPsCC. the group found that p16 expression was a strong prognostic factor in patients with genetics

Epidemiology: Human papillomavirus—a powerful predictor of survival in patients with oropharyngeal cancer

Epidemiology: Human papillomavirus—a powerful predictor of survival in patients with oropharyngeal cancer

Fertility: The importance of early referral to fertility preservation

with breast cancer undergoing ovarian stimulation for fertility preservation (by embryo or oocyte cryopreservation). 35 were referred for fertility preservation before surgery and 58 were referred after surgery. women who were referred to a fertility preservation specialist before breast surgery started chemotherapy, on average, 24 days earlier than women referred after surgery. moreover, “...they were able to freeze a larger number of eggs and embryos because a larger proportion could undergo a second embryo or egg freezing cycle,” oktay reports. indeed, nine patients in the presugery group (25.7%) versus one patient in the post-surgery group (1.7%) were able to have a second cycle of freezing. this FERTiliTy

Surgery: Laparoscopy versus laparotomy in early-stage endometrial cancer

the standard treatment for early-stage endometrial cancer is total abdominal hysterectomy (taH), generally carried out through laparotomy, with bilateral salpingo-oophorectomy. although this method is effective, the surgical procedure can be associated with considerable morbidity, because of a high incidence of obesity and other comorbidities seen in patients with endometrial cancer. Compared with taH, total laparoscopic hysterectomy (tlH) offers a less-invasive treatment approach and has been associated with a reduction in complications. Few randomized studies have compared the two techniques in patients with earlystage endometrial cancer and none has investigated morbidity. now, two studies report improved quality-of-life and health outcomes and reduced complications in this population of patients treated with tlH compared with taH. mourits and colleagues randomly assigned patients with stage i endometrial cancer to treatment with either taH (n = 96) or tlH (n = 187) in 21 medical centers in the netherlands. the team assessed the occurrence of major complications (intraoperatively and postoperatively) and minor complications, the treatment-related outcomes, and the quality-of-life in both groups. no marked difference in the incidence of major complications or minor complications was reported between the reasons why complications were so low in the tlH group is because all surgeons underwent an accreditation process and all patients had surgery with one of those highly-trained gynecological surgeons,” comments obermair. survival results from these two trials have not yet been published. these data, when available, together with the results of the present studies, will hopefully assist decision making about the introduction of a new surgical technique for the treatment of endometrial cancer.

Genetics: HER3 overexpression in breast cancer conveys a poor prognosis

a highly promising and clinically applicable candidate.” tumor samples from 4,046 patients with invasive breast carcinoma were assessed for expression of t1GFr family members Her1, Her2, Her3 and Her4. in 10% of these tumors, Her3 overexpression was identified and was significantly associated with decreased disease-specific survival. Furthermore, in tumors with normal Her1 and Her2 expression, Her3 conveyed a negative prognostic effect on breast cancer-specific survival. “Her3 may represent a target for anticancer therapy in this patient subset that otherwise do not express molecules targeted by current molecular treatments,” sam wiseman concludes.

Chemotherapy: Biomarkers of chemotherapy response in breast cancer

Profiling tumors for two important target-based biomarkers can help to accurately predict the response to anthracycline-containing chemotherapy in patients with breast cancer, according to a recent study. lead investigator Bent ejlertsen commented that by combining the biomarkers topoisomerase ii alpha (TOP2A) and tissue inhibitor of matrix metalloproteinases 1 (timP-1), “we were able to construct a profile identifying a larger proportion of patients as anthracycline-responsive than these markers did individually.” Human eGFr2 (Her2), TOP2A and timP-1 have all been identified as biomarkers that can predict the treatment outcome associated with anthracycline-containing chemotherapy. in the present study, ejlertsen and colleagues compared the predictive value of these biomarkers individually and in combination (Her2 with timP-1 or TOP2A with timP-1) in patients enrolled cHEMoTHERaPy Biomarkers of chemotherapy response in breast cancer

Genetics: N-cadherin—a target for prostate cancer therapy

the major cause of death in patients with prostate cancer is progression from androgen-dependent disease to castrationresistant disease. a new study has shown that this resistance is associated the expression of n-cadherin. therapeutic targeting of n-cadherin might delay the progression of prostate cancer, tanaka and colleagues report. in a gene-expression analysis of xenografts and tumor samples, n-cadherin expression was notably higher in castration-resistant prostate cancer than in androgen-dependant disease. moreover, the researchers found that n-cadherin expression in androgen-dependent cell lines seemed to encourage invasion, metastasis and progression to castration-resistant prostate cancer. the investigators treated castrationresistant cell lines in vitro with monoclonal antibodies against n-cadherin to determine whether this factor might be a potential genetics