Satraplatin: an orally available platinum analog for the treatment of cancer

Satraplatin is a novel, orally bioavailable, platinum anticancer drug. Platinum analogs form the mainstay of treatment for a number of cancers, including lung, ovarian, colorectal and head and neck cancer. A disadvantage of the currently marketed platinum analogs is that they must all be administered via intravenous infusion. In addition, their utility is often limited by toxicity, particularly neurotoxicity, ototoxicity and renal toxicity. Satraplatin has preclinical antitumor activity comparable with that of cisplatin and, clinically, has a more manageable side-effect profile. Satraplatin is active in lung, ovarian and prostate cancer, and appears to have good efficacy in combination with radiation for lung and head and neck cancer. Preclinical data suggest it may also be effective for the treatment of certain cisplatin-refractory tumors. A large, randomized Phase III trial is currently evaluating satraplatin in combination with prednisone for the treatment of patients with hormone-refractory prostate cancer whose disease has progressed following prior systemic therapy. Positive results from this trial would support regulatory approval for satraplatin for this indication. The availability of an active oral platinum agent, such as satraplatin, with few of the serious toxicities associated with traditional intravenous platinum compounds makes satraplatin an alternative to other platinum agents and a new treatment option in the oncologist’s armamentarium.     

Can patients with head and neck cancers invading carotid artery gain survival benefit from surgery?

Conclusion. Surgical treatment of carotid invasion may give an improved 2-year survival in selected patients without significant morbidity. Objective. To evaluate survival outcomes in patients with head and neck squamous cell carcinomas invading the carotid artery. Patients and methods. At the time of carotid invasion, 23 patients underwent surgery (n=11), chemoradiotherapy (n=6), or palliation (n=6). Surgical methods included carotid resection and ligation (n=5), carotid resection and reconstruction with saphenous vein (n=4), and peeling (n=2). Survival outcomes among different treatments were compared. Results. None of the 11 surgical patients experienced perioperative mortality or major neurologic complications. Three of these patients survived, but two had recurrent disease at last follow-up; their 2-year overall survival and disease-free survival rates were 24.5% and 18.2%, respectively. In contrast, all patients treated with chemoradiation or palliation died within 15 months. Median survival time was 16.5 months in the surgery group, 11.5 months in the chemoradiation group, and 3 months in the palliation group (p=0.025).     

Molecular biomarkers in HNSCC: prognostic and therapeutic implications

The prognosis of squamous cell carcinoma of head and neck (HNSCC) is influenced by many factors, such as performance status, TNM staging and pathological grading of differentiation. However, these factors are not sufficient for predicting outcome. Therefore, recent research has focused on the identification of molecular biomarkers. These markers help to stage patients in more meaningful prognostic groups and identify high-risk patients who may benefit from a more aggressive treatment approach. They also identify patients who are resistant to radiotherapy or chemotherapy, potentially avoiding the morbidity and cost of ineffective therapies. They can also identify patients with a high risk of recurrence who may benefit from chemoprevention. Finally, these markers may serve as targets for novel therapies, which would eventually change the outcome of HNSCC.     

Targeting epidermal growth factor receptor signaling in the treatment of head and neck cancer

In this review, key aspects of epidermal growth factor receptor (EGFR) biology and the fruitful translation of these fundamental findings into recent treatment advances in head and neck squamous cell cancer (HNSCC) are highlighted. In contrast to a number of contemporary reviews of the EGFR, many of which focus on colorectal and nonsmall cell lung cancer, this review discusses the EGFR as a validated therapeutic target in HNSCC. Recent data confirm a survival advantage for the addition of the anti-EGFR monoclonal antibody cetuximab to definitive radiation therapy in locoregionally advanced HNSCC patients, as well as palliative benefits for patients with incurable recurrent and metastatic HNSCC. Small-molecule EGFR tyrosine kinase inhibitors also show considerable promise in this disease, both alone and in combination with radiation and chemotherapy. Both classes of anti-EGFR agent are generally well tolerated, with side effects (notably skin rash) that are distinct from the toxicities of conventional chemotherapy. Ongoing clinical trials will more clearly define the role for EGFR inhibitors in all treatment phases of HNSCC.     

Predictive value of sentinel node biopsy in head and neck cancer

Conclusions. The negative predictive value (NPV) of sentinel lymph node biopsy (SNB) in this study was 95%. The accuracy of SNB compared to histopathologic evaluation of surgical specimen of subsequent neck dissection (ND) was 96%. Objective. To evaluate NPV of SNB in head and neck cancer. Patients and methods. This was a prospective clinical study comprising 35 patients (50 necks) with squamous cell carcinoma (SCC) of head and neck with clinically (cN0) and radiologically negative necks, without previous treatment, who underwent SNB with gamma probe and subsequent ND. The NPV, accuracy, sensitivity, and specificity of SNB were compared to histopathologic assessment of surgical specimens from NDs. Negative sentinel lymph nodes (SLNs) on histopathology were evaluated with step serial section (SSS) and immunohistochemistry (IHC). When a neck had a positive SLN, all lymph nodes of subsequent NDs were studied with SSS and IHC. Results. There were primaries of the oral cavity (n=24), lip (n=3), oropharynx (n=3), and larynx (n=5). All patients had detected SLNs. In all, 41 necks were SLN-negative on histopathologic evaluation but 2 (5%) had metastases in non-SLNs after ND. Of these 41 necks, SLNs were level Ib (26%), IIa (45%), III (21%), and IV (8%). Nine necks presented positive SLN on histopathologic evaluation, level Ib (n=3), IIa (n=5), and III (n=2), and subsequent NDs were negative on conventional histopathologic analysis, but after SSS and IHC, two presented micrometastases.     

Risk factors of avascular necrosis of the femoral head and fixation failure in patients with valgus angulated femoral neck fractures over the age of 50 years

IntroductionThe aim of our study was to identify the risk factors for avascular necrosis of the femoral head (AVN) and fixation failure (FF) after screw osteosynthesis in patients with valgus angulated femoral neck fractures.Patients and methodsWe conducted a retrospective study of 308 patients (mean age, 72.5 years, range, 50–97 years), with a mean follow-up of 21.4 months (range, 12–64 months). The risk for failure in treatment (FIT) associated with patient- and fracture-related factors was evaluated by logistic regression analyses.ResultsFIT was identified in 32 cases (10.3%): 22 cases (7.1%) of AVN and 10 cases (3.2%) of FF. Initial valgus tilt > 15° (p = 0.023), posterior tilt > 15° (p = 0.012), and screw sliding distance (p = 0.037) were significantly associated with FIT. FIT occurred in 7 patients (5.2%) with B1.2.1 fractures and 17 patients (48.6%) with B1.1.2 fractures (p < 0.001). The odds of FIT were 17-fold higher in patients with initial valgus and posterior tilts > 15° (B1.1.2) compared to patients with <15° of tilt in both planes (B1.2.1).ConclusionThe severity of initial deformity predicts AVN and FF in patients with valgus angulated femoral neck fractures. Patients with an initial valgus and posterior tilt > 15° are reasonable candidates for primary arthroplasty due to high risk of FIT.