Chemotherapy Research and Practice

A retrospective review was performed on patients with stable melanoma brain metastases treated with HD IL-2 therapy (720,000 IU/kg per dose intravenously; 14 doses, 2 cycles per course, maximum 2 courses) from January 1999 to June 2011 at Saint Louis University. There were 5 men and 3 women; median age was 52.2 years (26.8-61.1 years). One patient started treatment with lung lesions only (after resection of melanoma brain disease) and experienced partial response. Seven patients had brain metastases at treatment initiation...

Lomustine is a nitrosourea anticancer agent shown to be effective for treatment of childhood medulloblastoma. In silico substructure searches produced 17 novel nitrosourea agents analogous to lumustine and retaining activity for DNA alkylation and cytotoxic activity. The mean values for Log P, polar surface area, formula weight, number of oxygens & nitrogens, and rotatable bonds were 2.524, 62.89 Anstroms(2), 232.8, 5, and 2, respectively. All 17 agents have formula weight less than 450 and Log P less than 5, two criteria preferred for blood-brain barrier penetration...

Despite advances in neurosurgery and aggressive treatment with temozolomide (TMZ) and radiation, the overall survival of patients with glioblastoma (GBM) remains poor. Vast evidence has indicated that the nuclear factor NF- κ B is constitutively activated in cancer cells, playing key roles in growth and survival. Recently, Dehydroxymethylepoxyquinomicin (DHMEQ) has shown to be a selective NF- κ B inhibitor with antiproliferative properties in GBM. In the present study, the ability of DHMEQ to surmount tumor's invasive nature and therapy resistance were further explored...

High-risk prostate cancer represents a pretentious clinical problem since a significant number of its patients will relapse and progress after radical prostatectomy. Neoadjuvant chemotherapy may be valuable since its efficacy in hormone-resistant prostate cancer has been established. In this paper, we report studies of neoadjuvant chemotherapies that have been used in high-risk patients prior to radical prostatectomy. Even though the results regarding the prognostic surrogates are not significant, the effects on clinical and pathological outcomes are promising, while toxicity in most of the studies is in the expected field...

Human epidermal growth factor receptor 2 (HER2) is overexpressed in around 20-30% of breast cancer tumors. It is associated with a more aggressive disease, higher recurrence rate, and increased mortality. Trastuzumab is a HER2 receptor blocker that has become the standard of care for the treatment of HER2 positive breast cancer. The effectiveness of Trastuzumab has been well validated in research as well as in clinical practice. The addition of Trastuzumab to standard of care chemotherapy in clinical trials has been shown to improve outcomes for early stage as well as metastatic HER2 positive breast cancer...

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Chemotherapy has been used for cancer treatment already for almost 70 years by targeting the proliferation potential and metastasising ability of tumour cells. Despite the progress made in the development of potent chemotherapy drugs, their toxicity to normal tissues and adverse side effects in multiple organ systems as well as drug resistance have remained the major obstacles for the successful clinical use. Cytotoxic agents decrease considerably the quality of life of cancer patients manifesting as acute complaints and impacting the life of survivors also for years after the treatment...

HER3 (ErbB3) is a unique member of the human epidermal growth factor receptor (EGFR) family (ErbB family). It functions only through dimerization with other members of the ErbB family and modulates activity and sensitivity to targeted cancer therapies. This paper briefly describes the mechanism of HER3 in signal transduction and its potential role in acquired resistance to EGFR- and HER2-targeted therapies. We also consider recent developments in HER3-targeting therapeutics and their combination with inhibitors of other ErbB members in clinical applications...

Targeting of the EGF receptor (EGFR) has become a standard of care in several tumor types. In squamous cell carcinoma of the head and neck, monoclonal antibodies directed against EGFR have become a regular component of therapy for curative as well as palliative treatment strategies. These agents have anti-tumor efficacy as a single modality and have demonstrated synergistic tumor killing when combined with radiation and/or chemotherapy. While cetuximab has been the primary anti-EGFR monoclonal antibody used in the US, variant anti-EGFR monoclonal antibodies have been used in several clinical studies and shown benefit with improved toxicity profiles...

Colorectal cancer is the second most common malignancy among men and women in the United States, and the 5-year survival rate remains poor despite recent advances in chemotherapy and targeted agents. The mainstay of therapy for advanced disease remains the cytotoxic chemotherapy including 5-FU, irinotecan, and oxaliplatin. The USFDA approval and introduction of targeted therapies, including cetuximab and panitumumab (monoclonal antibodies targeting the epidermal growth factor receptor (EGFR)) and bevacizumab (monoclonal antibody targeting the vascular epithelial growth factor (VEGF)), has improved the median survival of patients with metastatic colorectal cancer to around 24 months...

Patients with metastatic colorectal cancer have a poor prognosis and present a challenge to clinicians. The role of the antiepidermal growth factor receptor (EGFR) pathway in tumorogenesis and tumor progression has been well defined. This paper will review the use of anti-EGFR monoclonal antibodies in the treatment of operable, as well as metastatic colorectal cancer both in the setting of KRAS mutation unselected patients and later in KRAS wild-type patients. Active investigations designed to further identify predictive biomarkers that may be potentially druggable are reviewed as well...

Squamous cell carcinoma of the head and neck (SCCHN) is a prevalent disease both in the United States and worldwide with an overall poor prognosis, in part due to limited activity of existing therapy. Primary therapy is largely dictated by the anatomical origin of the cancer and whether distant disease is present. Many patients with localized disease are treated with chemoradiotherapy, either in the definitive or adjuvant setting, and those with metastatic disease are treated with palliative chemotherapy. The chemotherapy used in SCCHN can be toxic, whether given with radiation or alone...

Background. The aim of our study was to evaluate the effects of neoadjuvant platinum-based radiochemotherapy (RCT) in patients with maxillary sinus squamous cell carcinoma and to compare the results with other multimodality treatment concepts for advanced-stage maxillary sinus carcinoma in the literature. Methods. In total, 53 patients with squamous cell carcinoma of the maxillary sinus were reviewed retrospectively. All patients received a neoadjuvant RCT containing either cisplatin or carboplatin followed by radical surgery...

Epidermal growth factor receptor (EGFR) inhibition has now been well established as an effective treatment for various cancers. The EGFR belongs to the ErbB family of tyrosine kinase receptors which regulate tumor cell differentiation, survival and proliferation. Activation of EGFR drives tumorigenesis in lung, head and neck, colorectal and pancreatic cancers. Irrespective of the type of cancer being treated and the mechanism by which tumor EGFR drives tumorigenesis, the major side effect of EGFR inhibition is a papulopustular (also described as maculopapular or acneiform) rash which occurs in about two thirds of treated patients...

"Mucositis" is the clinical term used to describe ulceration and damage of the mucous membranes of the entire gastrointestinal tract (GIT) following cytotoxic cancer chemotherapy and radiation therapy common symptoms include abdominal pain, bloating, diarrhoea, vomiting, and constipation resulting in both a significant clinical and financial burden. Chemotherapeutic drugs cause upregulation of stress response genes including NFκB, that in turn upregulate the production of proinflammatory cytokines such as interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α)...

The epidermal growth factor receptor (EGFR) is a well-characterized oncogene that is frequently activated by somatic kinase domain mutations in non-small cell lung cancer (NSCLC). EGFR TKIs are effective therapies for NSCLC patients whose tumors harbor an EGFR activating mutation. However, EGFR TKI treatment is not curative in patients because of both primary and secondary treatment resistance. Studies over the last decade have identified mechanisms that drive primary and secondary resistance to EGFR TKI treatment...

Background. The standard initial management of patients with locally advanced pharyngolaryngeal presenting with stridor is tracheostomy. Tracheostomy has been shown to negatively impact cancer-related outcomes. Methods. Retrospective analysis of prospectively collected data of 9 patients, who underwent induction chemotherapy with the aim of prevention of tracheostomy. Presenting features, time to resolution of stridor, and further management are reported. Results. Eight out of 9 patient received chemotherapy within 12 hours of presentation with stridor...

The therapeutic performance of oxaliplatin can be improved by incorporating the central cis-dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt) motif into the core cross-linked block copolymer micelles. We describe here the preparation, cellular uptake, and in vivo evaluation of core cross-linked micelles loaded with DACHPt. Stable drug-loaded micelles were prepared at high drug loading (~25 w/w%) and displayed a considerably increased in vitro cytotoxicity compared to free oxaliplatin against A2780 ovarian cancer cells...

Resistance to the HER2-targeted antibody trastuzumab is a major clinical concern in the treatment of HER2-overexpressing metastatic breast cancer. Increased expression or signaling of the insulin-like growth factor-I receptor (IGF-IR) has been reported in a subset of cell lines and clinical samples derived from trastuzumab-resistant breast cancers. Genetic and pharmacologic inhibition of IGF-IR signaling has been shown to improve response to trastuzumab in trastuzumab-naïve and trastuzumab-resistant models...

Anticancer drug resistance is a multifactorial process that includes acquired and de novo drug resistances. Acquired resistance develops during treatment, while de novo resistance is the primary way for tumor cells to escape chemotherapy. Tumor microenvironment has been recently shown to be one of the important factors contributing to de novo resistance and called environment-mediated drug resistance (EMDR). Two forms of EMDR have been described: soluble factor-mediated drug resistance (SFM-DR) and cell adhesion-mediated drug resistance (CAM-DR)...