Preoperative chemoradiotherapy induces multiple pathways related to anti-tumour immunity in rectal cancer.

BACKGROUND: Rectal cancer treated with preoperative radiotherapy (RT) provides an interesting model to study changes induced on cancer cell immuno-phenotype that could be exploited by immunotherapy interventions to improve prognosis. MATERIALS AND METHODS: We assessed the expression of HLA-class-I, ß2-microglobulin, TAP1, PD-L1 and STING/IFNß in preoperative biopsies and respective post-RT surgical specimens from patients with rectal cancer (n = 27). The effect of radiation was further investigated in colorectal adenocarcinoma cell lines HT-29 and Caco-2. RESULTS: Rectal carcinomas exhibited extensive loss of expression of HLA-Class-I related molecules, which was restored in post-irradiation surgical specimens (P < 0.0001). RT induced the expression of IFNß and STING in cancer cells and tumour-infiltrating lymphocytes (P < 0.0001). In in vitro experiments, irradiation with 4 Gy or 10 Gy induced the expression of HLA-class-I protein (P < 0.001). PD-L1 levels were transiently induced for two days (P < 0.001). cGAS, STING, IFNß and the downstream genes (MX1, MX2, UBE2L6v2, IFI6v2 and IFI44) mRNA levels significantly increased after 3 × 8 Gy or 1 × 20 Gy irradiation (P < 0.001). TREX1 mRNA levels remained unaltered. CONCLUSIONS: RT induces the IFN-type-I pathway and the expression of HLA-class-I molecules on rectal carcinoma. The transient induction of PD-L1 expression suggests that long-course daily RT may sustain increased PD-L1 levels. Anti-PD-L1/PD-1 immunotherapy could block this immunosuppressive pathway.

Nanoparticle-Mediated Hyperthermia and Cytotoxicity Mechanisms in Cancer.

Hyperthermia has the potential to damage cancerous tissue by increasing the body temperature. However, targeting cancer cells whilst protecting the surrounding tissues is often challenging, especially when implemented in clinical practice. In this direction, there are data showing that the combination of nanotechnology and hyperthermia offers more successful penetration of nanoparticles in the tumor environment, thus allowing targeted hyperthermia in the region of interest. At the same time, unlike radiotherapy, the use of non-ionizing radiation makes hyperthermia an attractive therapeutic option. This review summarizes the existing literature regarding the use of hyperthermia and nanoparticles in cancer, with a focus on nanoparticle-induced cytotoxicity mechanisms.

Successful Treatment of a Locally Recurrent and Metastatic Malignant Phyllodes Tumor with Accelerated Radiotherapy and Nab-Paclitaxel, Cisplatin, and Liposomal Doxorubicin Chemotherapy.

Phyllodes tumors are rare breast lesions of fibroepithelial origin. Malignant transformation with metastases is linked with poor prognosis. We present a case of a 62-year-old woman with a recurrent malignant phyllodes tumor of the breast and lung metastases. The patient was originally presented with a borderline phyllodes tumor (7.4 cm) of the left breast, treated with wide local excision. A year later, the patient returned with palpable left breast masses. On PET-CT, increased uptake of 18F-FDG by large breast tumors was evident. A right lung lesion of metastatic origin was also present. A simple left breast mastectomy was performed. Histopathological report described 2 malignant phyllodes tumors (7 cm and 6.5 cm). One month later, during the CT simulation for radiotherapy planning, encysted fluid in the chest wall and 2 additional pulmonary lesions of the right lung were identified, confirming progressive lung metastatic disease. Both the chest wall and the regional lymph node area were irradiated with hypofractionated and accelerated radiotherapy. Biweekly chemotherapy with albumin-bound paclitaxel, cisplatin, and liposomal doxorubicin was also prescribed at the start of radiotherapy for 12 cycles. At the end of chemotherapy, complete regression of lung metastases was achieved, and there was no evidence of local recurrence. Within 2 years of follow-up, the patient is free of disease and treatment-related toxicities. Accelerated hypofractionated radiotherapy is effective in the locoregional control of malignant phyllodes tumors. The combination of cisplatin with nab-paclitaxel and liposomal doxorubicin chemotherapy has acceptable toxicity and is highly effective in eradicating metastatic lesions.

Quality of Life, Anxiety, and Depression in the Head-and-Neck Cancer Patients, Undergoing Intensity-Modulated Radiotherapy Treatment.

AIMS: The aim of this study is to investigate and compare distress and quality-of-life parameters among head-and-neck cancer patients who underwent intensity-modulated radiotherapy (IMRT). SUBJECTS AND METHODS: The patients' sample consists of 55 individuals under IMRT treatment. Three questionnaires (Quality of Life Questionnaire [QLQ]-C30 and QLQ-H and N35) of the European Organization for the Research and Treatment of Cancer and the Greek Hospital Anxiety and Depression Scales were used. RESULTS: Functioning and symptoms scales measured a week before the scheduled treatment worsen significantly until the end of the treatment and at the 3-month follow-up, tend to revert to their pretreatment values. CONCLUSIONS: Our results showed that all parameters (functioning scales, symptoms scales, and G-HAD subscales) worsen from the start to the end treatment and tend to revert to their pretreatment values after a 3-month period.

Reliability and Validity of the Greek Version of Patient Generated-Subjective Global Assessment in Cancer Patients.

The authors sought to determine the reliability and validity of psychometric properties of the Greek Patient-Generated Subjective Global Assessment (PG-SGA) in cancer patients attending a palliative care unit. The scale was translated into Greek. The study took place in an outpatient palliative care unit and 238 cancer patients completed the nutrition assessment. For treatment effect, the index was administered to 164 patients, whereas for the test of the instrument's robustness to 100 patients. Both assessments took place 15 days after the baseline assessment. Ninety-three patients were well-nourished, 104 were moderately malnourished, and 41 were severely malnourished. Reliability was assessed by the internal consistency and test-retest of the instrument. Validity was assessed with construct validity using the PG-SGA items, treatment effect, and criterion validity. Weight loss, physical examination, activities and function, and symptoms were predictors to the classification. Mean values in male patients classified as severely malnourished had the lowest values in all objective parameters except serum albumin, whereas severely malnourished female patients had the lowest values in all objective parameters except serum albumin and arm muscle circumference (AMC). Values of serum transferrin, AMC, and body mass index were significantly lower in patients classified as severely malnourished. The Greek PG-SGA is a psychometrically sound assessment in Greek cancer patients.

Caregivers' attachment patterns and their interactions with cancer patients' patterns.

PURPOSE: To provide a brief review of the empirical literature regarding the attachment style of the cancer patients' caregivers as well as the link between attachment, caregiving, and care-receiving behaviors are defined. METHODS: An extensive systematic electronic review (Medline, PsycINFO, and Attachment Theory Website (ATW)) and subsequent examination of reference lists were carried out to retrieve published articles up to 2011, using attachment and cancer in combination with caregiver, spouse, dyad, and family as the key words. The titles, abstracts, or full articles, if necessary, were reviewed to determine whether the articles met the eligibility criteria. RESULTS: Eighty-seven studies have been identified, including research articles, books, and chapters in books. CONCLUSIONS: The attachment style of a caregiver can influence how they respond to a patient's needs. Studies have found that attachment anxiety or avoidance is more likely to interfere with effective and sensitive caregiving.

Splenic irradiation as palliative treatment for symptomatic splenomegaly due to secondary myelofibrosis: a multi-institutional experience.

PURPOSE: To evaluate the impact of splenic irradiation as a palliative treatment for symptomatic splenomegaly due to secondary myelofibrosis. METHODS: Seventeen patients with chronic myelogenous leukemia and 3 with idiopathic polycythaemia presented with splenomegaly, splenic pain and anemia. Due to symptomatic splenomegaly, despite first-line treatment, the patients underwent splenic irradiation. Two patients received two different schedules of external radiotherapy (580 cGy in 5 fractions and 600 cGy in 6 fractions). Eight patients received 980 cGy in 14 fractions. Ten patients received two courses of 360 cGy in 6 fractions, 3 months apart. Median follow-up was 12 months post irradiation. RESULTS: The patients showed excellent response to treatment one month post-radiotherapy, while treatment was well tolerated without severe toxicity. The dimensions of the spleen decreased significantly. Pain-related Visual Analogue Score (VAS) regressed after completion of irradiation. During 12-month follow-up all patients maintained the benefit of radiotherapy. CONCLUSION: This study indicates that splenic irradiation could be a safe and effective palliative treatment for symptomatic splenomegaly due to secondary myelofibrosis.

The impact of intermediate time between chemotherapy and hypofractionated radiotherapy to the radiation induced skin toxicity for breast adjuvant treatment.

To evaluate the impact of intermediate time between chemotherapy and radiotherapy (ITCR) to skin toxicity for a hypofractionated irradiation schedule. Forty-four patients with stage I-II invasive breast cancer receiving postoperative radiotherapy (RT) after lumpectomy and axillary dissection were studied. All patients received RT with 6 MV linear accelerator (LINAC) with a total tumor dose of 53 Gy (Equivalent dose-EQD2- 60 Gy), 2.65 Gy per fraction, in 20 fractions. All patients received six cycles of cyclophosphamide methotrexate fluorouracil chemotherapy i.v. every 21 days. Acute and late effects and cosmetic results were assessed using the European Organization for Research and Treatment of Cancer and Radiation Therapy Oncology Group (EORTC/RTOG) Rating System. The mean follow-up was 7 years. The spearman rho test showed that there was a significant correlation between short ITCR and acute skin toxicity 3 months post RT, by means of acute radiation induced morbidity. None of the related late-toxicity parameters was correlated with the ITCR. However, there was significantly higher acute toxicity when the ITCR was less than 20 days (p < 0.05). We may suggest that when a hypofractionated irradiation schedule is used for breast cancer patients, then the ITCR should be more than 20 days from chemotherapy.

Radiotherapy and Testicular Function: A Comprehensive Review of the Radiation-Induced Effects with an Emphasis on Spermatogenesis.

This comprehensive review explores the existing literature on the effects of radiotherapy on testicular function, focusing mainly on spermatogenic effects, but also with a brief report on endocrine abnormalities. Data from animal experiments as well as results on humans either from clinical studies or from accidental radiation exposure are included to demonstrate a complete perspective on the level of vulnerability of the testes and their various cellular components to irradiation. Even relatively low doses of radiation, produced either from direct testicular irradiation or more commonly from scattered doses, may often lead to detrimental effects on sperm count and quality. Leydig cells are more radioresistant; however, they can still be influenced by the doses used in clinical practice. The potential resultant fertility complications of cancer radiotherapy should be always discussed with the patient before treatment initiation, and all available and appropriate fertility preservation measures should be taken to ensure the future reproductive potential of the patient. The topic of potential hereditary effects of germ cell irradiation remains a controversial field with ethical implications, requiring future research.

Lymphopenia Induced by Different Neoadjuvant Chemo-Radiotherapy Schedules in Patients with Rectal Cancer: Bone Marrow as an Organ at Risk.

Radiotherapy (RT)-induced lymphopenia may hinder the anti-tumor immune response. Preoperative RT or chemo-RT (CRT) for locally advanced rectal cancer is a standard therapeutic approach, while immunotherapy has been approved for mismatch repair-deficient rectal tumors. We retrospectively analyzed 98 rectal adenocarcinoma patients undergoing neoadjuvant CRT with VMAT (groups A, B, C) or IMRT (group D) techniques, with four different RT schemes: group A (n = 24): 25 Gy/5 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group B (n = 22): 34 Gy/3.4 Gy/fraction, with a 1-week treatment break after the first five RT fractions; group C (n = 20): 46 Gy/2 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group D (n = 32): 45 Gy/1.8 Gy/fraction followed by 5.4 Gy/1.8 Gy/fraction to the rectal tumor. We examined the effect of the time-corrected normalized total dose (NTD-T) to the BM on lymphopenia. Groups A and B (hypofractionated RT) had significantly higher lymphocyte counts (LCs) after RT than groups C and D (p < 0.03). An inverse association between the LCs after RT and NTD-T was demonstrated (p = 0.01). An NTD-T threshold of 30 Gy delivered to 30% of the BM volume emerged as a potential constraint for RT planning, which could be successfully integrated in the RT plan. Hypofractionated and accelerated RT schemes, and BM-sparing techniques may reduce lymphocytic damage and prove critical for immuno-RT clinical trials.

Fe3O4 and Fe3O4core Aushell-based Hyperthermia Reduces Expression of Proliferation Markers Ki-67, TOP2A and TPX2 in a Human Breast Cancer Cell Line.

BACKGROUND/AIM: Hyperthermia represents an adjuvant local anticancer strategy which relies on the increase of temperature beyond the physiological level. In this study, we investigated the anticancer potential of Fe3O4 and Fe3O4core Aushell nanoparticles as hyperthermic agents in terms of cytotoxicity and studied the expression of cellular markers of proliferation (changes in mRNA levels via real-time polymerase chain reaction). MATERIALS AND METHODS: The human breast cancer cell line SK-BR-1 was incubated with either Fe3O4 or Fe3O4core Aushell nanoparticles stabilized with tryptophan, prior to hyperthermia treatment. The normal HEK293 cell line was used as a control. Toxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay to estimate possible toxic effects of the tested nanoparticles. After RNA extraction and cDNA synthesis, mRNA expression of three indicators of proliferation, namely marker of proliferation Ki-67, DNA topoisomerase II alpha (TOP2A) and TPX2 microtubule nucleation factor (TPX2), was investigated. RESULTS: At each concentration tested, Fe3O4core Aushell nanoparticles showed greater toxicity compared to Fe3O4, while SK-BR-3 cells were more susceptible to their cytotoxic effects compared to the HEK293 cell line. The expression of Ki-67, TOP2A and TPX2 was reduced in SK-BR-3 cells by both Fe3O4 or Fe3O4core Aushell nanoparticles compared to untreated cells, while the only observed change in HEK293 cells was the up-regulation of TOP2A. CONCLUSION: Both Fe3O4core Aushell and Fe3O4 NPs exhibit increased cytotoxicity to the cancer cell line tested (SK-BR-3) compared to HEK293 cells. The down-regulation in SK-BR-3 cells of the three proliferative markers studied, Ki-67, TOP2A and TPX2, after incubation with NPs suggests that cells that survived thermal destruction were not actively proliferating.

Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients.

PURPOSE: The aim of this project was to review the available literature and define clinical practice guidelines for the use of anti-inflammatory agents for the prevention and treatment of oral mucositis in cancer patients. MATERIALS AND METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for use of each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible. RESULTS: Forty-one papers were reviewed. There was sufficient evidence to recommend the use of benzydamine mouthwash for the prevention of oral mucositis in head and neck cancer patients receiving moderate-dose radiation therapy (up to 50 Gy), without concomitant chemotherapy. A new suggestion was developed against the use of misoprostol mouthwash for the prevention of oral mucositis in head and neck cancer patients receiving radiation therapy. Positive results were reported for some other anti-inflammatory agents. However, no guidelines were able to be developed for any other agents due to insufficient and/or conflicting evidence. CONCLUSIONS: The use of anti-inflammatory agents continues to be a promising strategy for the prevention and treatment of oral mucositis. Additional well-designed studies are needed to examine the use of this class of agents for oral mucositis.

Systematic review of amifostine for the management of oral mucositis in cancer patients.

PURPOSE: The aim of this study was to review the available literature from 1966 until December 31, 2010 and define clinical practice guidelines for the use of amifostine for the prevention and treatment of oral mucositis in cancer patients. METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for the use of amifostine, in each cancer treatment setting was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, or no guideline possible. RESULTS: Thirty papers were reviewed for evidence on amifostine as an intervention for oral mucositis. No guideline was possible for amifostine in any cancer treatment setting due to inadequate and conflicting evidence. CONCLUSION: Review of the amifostine studies for the prevention and treatment of oral mucositis has found insufficient evidence to support its use in any cancer treatment setting for this purpose. Additional well-designed research is needed to clarify the role of amifostine as an intervention for oral mucositis.

Well-differentiated hand liposarcoma with bone metastases treated successfully with zoledronic Acid.

BACKGROUND: Well-differentiated liposarcomas of the upper extremities, such as the hand or forearm, are extremely rare and are commonly misdiagnosed and considered benign. They are frequently reported as having low metastatic potential. CASE REPORT: We report the case of a 58-year-old man with well-differentiated hand liposarcoma and diffuse bone metastases. The patient initially presented with a tumor of the thenar eminence and was treated with marginal surgical excision and external beam irradiation. 4 months after this treatment, soft tissue local recurrence and skeletal metastases were detected. Zoledronic acid treatment (4 mg per month) was initiated, and both the tumor and the metastases regressed. The patient remains cancer-free 3.5 years after diagnosis of the metastatic disease. CONCLUSION: Significant metastatic disease can develop in patients with well-differentiated liposarcomas. The beneficial effect of zoledronic acid observed in this case may be related to its anticancer properties, as described in phase III trials in various tumor types.

Is Locally Advanced Head-Neck Cancer One More Candidate for Accelerated Hypofractionation?

BACKGROUND/AIM: Hypofractionated accelerated radiotherapy (HypoAR) is widely applied for the treatment of early laryngeal cancer. Its role in locally advanced head-neck cancer (LA-HNC) is unexplored. PATIENTS AND METHODS: We present results of a prospective trial on 124 patients with LA-HNC, treated with radio-chemotherapy with three different HypoAR fractionations (3.5 Gy/day × 14-15 fractions, 2.7 Gy/day × 20-21 fractions, and 2.5 Gy/day × 21-22 fractions). RESULTS: Protraction of the overall treatment time due to oropharyngeal mucositis was enforced in 18/57 laryngeal, 6/19 nasopharyngeal, and 15/48 cancer patients with other tumors. Regarding late toxicities, laryngeal edema grade 3 was noted in 5/57 patients with laryngeal cancer, while severe dysphagia was noted in 4/124 and tracheoesophageal fistula formation in 1/124 patients. The complete response rates obtained were 73%, 84%, and 67% in patients with laryngeal, nasopharyngeal, and other tumors, respectively. The 3-year locoregional progression-free survival was 58%, 73%, and 55%, respectively. CONCLUSION: HypoAR chemoradiotherapy is feasible, with acceptable early and late radiotherapy toxicities, response rates and LPFS.

Complementary Therapies for Patients with Cancer: Reflexology and Relaxation in Integrative Palliative Care. A Randomized Controlled Comparative Study.

Objectives: Comparison of the effects of reflexology and relaxation on pain, anxiety, and depression, and quality of life (QoL) of patients with cancer. Design: A stratified random sample was selected, using an experimental design. Location: An outpatient Palliative Care Unit in Attica, Greece. Subjects: 88 patients suffering with cancer. Interventions: The sample was randomly divided into two equal groups, a reflexology and a relaxation group. The number of interventions for both groups was six 30-min weekly sessions. Outcome measures: The Greek Brief Pain Inventory (G-BPI) was used to measure pain, the Greek Hospital Anxiety and Depression Scale for screening anxiety and depression, and finally the Short Form Health Survey was used to measure QoL. Measurements of the above tools were taken three times in both groups as follows: preintervention, at fourth and at sixth week of intervention. Results: Anxiety and depression for both groups exhibited a statistically significant decrease during the observation period (p < 0.001, η2 > 0.25) but at the sixth week, there was a more significant decrease in the reflexology group compared with the relaxation group (p = 0.062, η2 = 0.044 vs. p = 0.005, η2 = 0.096 for anxiety), (p = 0.006, η2 = 0.094 vs. p = 0.001, η2 = 0.138 for depression). QoL physical and mental component measurements were significantly greater for the reflexology group (p < 0.001, η2 = 0.168 and p = 0.017, η2 = 0.071, respectively). The baseline-to-sixth week G-BPI measurements were markedly decreased for the reflexology group (p = 0.207, η2 = 0.020). Conclusions: Both interventions, relaxation and reflexology, seemed to be effective in decreasing anxiety and depression in patients with cancer. However, reflexology was found to be more effective in improving QoL (physical component) and to have a greater effect on pain management than relaxation.

In vitro effect of hyperthermic Ag and Au Fe3O4 nanoparticles in cancer cells.

PURPOSE: To investigate the anti-cancer efficacy of hyperthermic Ag and Au Fe3O4 core nanoparticles via cytotoxicity study (MTT assay) and the underlying molecular mechanism of action (changes in gene expression via quantitive real time PCR (qRT-PCR). METHODS: HEK293, HCT116, 4T1 and HUH7 human cell lines and 4T1 musculus mammary gland cell line were incubated with Fe3O4 core Ag(Au) shell nanoparticles (NPs) prior to a hyperthermia session. MTT assay was performed to estimate the cytotoxic effects of these NPs. RNA extraction and cDNA synthesis followed so as to quantify mRNA fold change of hsp-70, p53, bcl-2 and casp-3 via qRT-PCR. RESULTS: Fe3O4 core Au shell (concentrations of 400 and 600µg/mL) produced the greatest reduction of viability on HCT116 and 4T1 cells while Fe3O4 core Ag shell (200, 400 and 600µg/mL) reduce viability on HUH7 cells. Hsp-70, p53 and casp-3 were up-regulated while bcl-2 was downregulated in most cases. CONCLUSIONS: Fe3O4 core Ag (Au) shell induced apoptosis on cancer cells (HCT116 and HUH7) via the p53/bcl-2/casp-3 pathway. 4T1 cells also underwent apoptosis via a p53-independent pathway.

Treatment of early uterine sarcomas: disentangling adjuvant modalities.

Uterine sarcomas are a rare group of neoplasms with aggressive clinical course and poor prognosis. They are classified into four main histological subtypes in order of decreasing incidence: carcinosarcomas, leiomyosarcomas, endometrial stromal sarcomas and "other" sarcomas. The pathological subtype demands a tailored approach. Surgical resection is regarded as the mainstay of treatment. Total abdominal hysterectomy and bilateral salpingo-oophorectomy represents the standard treatment of uterine sarcomas. Pelvic and para-aortic lymph node dissection in carcinosarcomas is recommended, given their high incidence of lymph node metastases, and may have a role in endometrial stromal sarcomas. Adjuvant radiation therapy has historically been of little survival value, but it appears to improve local control and may delay recurrence. Regarding adjuvant chemotherapy, there is little evidence in the literature supporting its use except for carcinosarcomas. However, more trials are needed to address these issues, especially, their sequential application. Patients with uterine sarcomas should be referred to large academic centers for participation in clinical trials.

Temozolomide with radiation therapy in high grade brain gliomas: pharmaceuticals considerations and efficacy; a review article.

Malignant gliomas (glioblastoma multiforme and anaplastic astrocytoma) which have a combined incidence of 5-8/100,000 population, represent the most common primary central nervous system tumors. The treatment outcomes even with aggressive approach including surgery, radiation therapy and chemotherapy are dismal with median reported survival is less than 1 year. Temozolomide is a new drug which has shown promise in treating malignant gliomas and other difficult-to-treat tumors. This drug is a per os (p.o) imidazotetrazine second-generation alkylating agent which represents the leading compound in a new class of chemotherapeutic agents that enter the cerebrospinal fluid and do not require hepatic metabolism for activation. The efficacy of temozolomide was tested in vitro studies and has demonstrated schedule-dependent antitumor activity against highly resistant malignancies, including high-grade glioma (HGG). In addition, in clinical studies, temozolomide consistently demonstrates reproducible linear pharmacokinetics with approximately 100% p.o. bioavailability, noncumulative minimal myelosuppression that is rapidly reversible, and activity against a variety of solid tumors in both children and adults. Moreover, preclinical studies have evaluated the combination of temozolomide with other alkylating agents and inhibitors of the DNA repair protein O(6)-alkylguanine alkyltransferase to overcome resistance to chemotherapy in malignant glioma and malignant metastatic melanoma. At the present time temozolomide is approved in the United States for the treatment of adult patients with refractory anaplastic astrocytoma and, in the European Union, for treatment of glioblastoma multiforme showing progression or recurrence after standard therapy. Temozolomide's characteristics which make it a candidate for a wide range of clinical testing to evaluate the potential of combination treatments in different tumor types are its predictable bioavailability and minimal toxicity. An overview of the mechanism of action of temozolomide and a summary of results from more important randomized controlled clinical trials in high grade gliomas are presented here.

Efficacy of the oral fluorouracil pro-drug capecitabine in cancer treatment: a review.

Capecitabine (Xeloda) was developed as a pro-drug of fluorouracil (FU), with the aim of improving tolerability and intratumor drug concentrations through its tumorspecific conversion to the active drug. The purpose of this paper is to review the available information on capecitabine, focusing on its clinical effectiveness against various carcinomas. Identification of all eligible English trails was made by searching the PubMed and Cochrane databases from 1980 to 2007. Search terms included capecitabine, Xeloda and cancer treatment. Nowadays, FDA has approved the use of capecitabine as a first line therapy in patients with metastatic colorectal cancer when single-agent fluoropyrimidine is preferred. The drug is also approved for use as a single agent in metastatic breast cancer patients who are resistant to both anthracycline and paclitaxel-based regimens or when further anthracycline treatment is contraindicated. It is also approved in combination with docetaxel after failure of prior anthracycline-based chemotherapy. In patients with prostate, pancreatic, renal cell and ovarian carcinomas, capecitabine as a single-agent or in combination with other drugs has also shown benefits. Improved tolerability and comparable efficacy, compared with the intravenous FU/LV combination, in addition to its oral administration, make capecitabine an attractive option for the treatment of several types of carcinomas.