Vassilios Kouloulias

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

PurposeThe 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.MethodsA 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.ResultsThirty 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.ConclusionReview 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.

Brachytherapy for Prostate Cancer: A Systematic Review

Low-dose rate brachytherapy has become a mainstream treatment option for men diagnosed with prostate cancer because of excellent long-term treatment outcomes in low-, intermediate-, and high-risk patients. To a great extend due to patient lead advocacy for minimally invasive treatment options, high-quality prostate implants have become widely available in the US, Europe, and Japan. High-dose-rate (HDR) afterloading brachytherapy in the management of localised prostate cancer has practical, physical, and biological advantages over low-dose-rate seed brachytherapy. There are no free live sources used, no risk of source loss, and since the implant is a temporary procedure following discharge no issues with regard to radioprotection use of existing facilities exist. Patients with localized prostate cancer may benefit from high-dose-rate brachytherapy, which may be used alone in certain circumstances or in combination with external-beam radiotherapy in other settings. The purpose of this paper is to present the essentials of brachytherapies techniques along with the most important studies that support their effectiveness in the treatment of prostate cancer.

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 tumor-specific 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.

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, radiaton 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 O6-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.

LONG-TERM CANCER PAIN MANAGEMENT IN MORPHINE PRE-TREATED AND OPIOID NAIVE PATIENTS WITH TRANSDERMAL FENTANYL

There is emerging data supporting the use of TTS‐F (transdermal therapeutic system‐fentanyl) in opioid naive patients. Our study examines the safety and efficacy of TTS‐F in the long‐term control of cancer pain in opioid naive patients and those transferring from oral morphine. Pain was assessed in 589 patients (Group A: 268 opioid naive, Group B: 321 transferring from morphine) using a Visual Analogue Scale (VAS; 0–10), based on selected questions from the Greek Brief Pain Inventory (GBPI). Overall treatment satisfaction was assessed on a 4‐point scale. Quality of Life (QOL) and ECOG (0–4) status were also recorded. These were assessed in relation to TTS‐F dose, pain type (neuropathic, combined, nociceptive), concomitant use of anti‐inflammatory drugs and other demographic data. Of 589 patients, 59 (10%) withdrew as a result of inadequate pain satisfaction or for other reasons. There were no discontinuations due to side effects; no Grade 3–4 events occurred. A total of 530 continued on‐study, 211 patients died during study period and 295 departed; all (506; 89%) were satisfied with their pain relief. Analysis of patients at baseline, 28 days, 6 and 12 month time points (n = 153 Group A; n = 214 Group B) with respect to QOL and pain measures indicated a statistically significant (p < 0.001) improvement in all measures across time independent of pain type, or any other patient characteristic(s). In patients with intolerable pain, transfer to TTS‐F offers an efficient and safe long‐term analgesic option. TTS‐F offers durable long‐term maintenance of pain relief with acceptable side effects in opioid naive patients. In general, TTS‐F as a first line analgesic approach for carefully selected and monitored patients experiencing moderate to severe cancer pain should be considered.

Dermatitis during radiation for vulvar carcinoma: prevention and treatment with granulocyte-macrophage colony-stimulating factor impregnated gauze

The aim of this study was to determine the effectiveness of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) impregnated gauze in preventing or healing radiation‐induced dermatitis. Sixty‐one patients were irradiated for vulvar carcinoma. Thirty‐seven applied steroid cream at irradiated areas throughout radiotherapy (Group A) and 24 patients applied additionally GM‐CSF impregnated gauze (40μg/cm2 of skin‐irradiated area, twice per day) in addition to the steroid cream, after 20Gy of irradiation (Group B). The score of skin reactions (P=0.008, chi2 test) and the time interval of radiotherapy interruption (P=0.037, Mann‐Whitney U test) were statistically significantly reduced in Group B patients. Multivariate analysis of variance showed for this group not only a significant reduction in the Sum of Gross Dermatitis Scoring (P<0.001, adjusted for Duration of Dermatitis) but also a significant reduction of the healing time (P=0.02, adjusted for Sum of Gross Dermatitis Scoring). The pain grading was less (P=0.014, chi2 test) and pain reduction was noticed sooner after the application of GM‐CSF impregnated gauze (P=0.0017, Mann‐Whitney U test). Multivariate logistic regression analysis showed that the only significant effect on dermatitis score is due to Body Mass Index (P=0.034) and the application of GM‐CSF (P=0.008). GM‐CSF impregnated gauze can be effective in preventing and healing radiation‐induced dermatitis and in reducing the interruption intervals of radiotherapy for vulvar carcinomas.

Male breast carcinoma: epidemiology, risk factors and current therapeutic approaches.

Male breast cancer is a very rare disease with an incidence of about 0.5-1% comparing with the one of female breast cancer but relatively little is known about its cause. Treatment strategies for breast cancer in males are derived from studies performed among females. The probable reasons behind the frequent, late diagnoses presented at stages III or IV might be the lack of awareness. The rarity of the disease precludes large prospective randomized clinical trials. This study reviews male breast cancer and its risk factors, recommendations for diagnosis and the management of patients with male breast cancer.

Quality assurance in radiotherapy

In 1999, the European Organisation for Research and Treatment of Cancer (EORTC), being a European pioneer in the field of cancer research as well as in quality assurance (QA), launched an Emmanuel van der Schueren fellowship for QA in radiotherapy. In this paper, the work that has been done during the first E. van der Schueren fellowship is reported, focusing on four phase III EORTC clinical trials: 22921 for rectal cancer, 22961 and 22991 for prostate cancer and 22922 for breast cancer. A historical review of the QA programme of the EORTC Radiotherapy group during the past 20 years is included.

Therapeutics Interventions with Anti-Inflammatory Creams in Post Radiation Acute Skin Reactions: A Systematic Review of Most Important Clinical Trials

The majority of cancer patients will receive radiation therapy treatment at some stage during their malignancy. An acute skin reaction represents a common post radiation side effect with different grade of severity. In order to investigate the optimal methods to prevent and manage acute skin reactions related to radiation therapy we have conducted a systematic review on this topic. It seems that skin washing, including gentle washing with water alone with or without mild soap, should be permitted in patients receiving radiation therapy, to prevent acute skin reaction. In addition, a low dose (i.e., 1%) corticosteroid cream may be beneficial in the reduction of itching and irritation. We have concluded that there is insufficient evidence to support or refute specific topical or oral agents for the prevention or management of acute skin reaction. There is a need for further research to review treatments that have produced promising results in the reviewed research studies and to evaluate other commonly recommended topical treatments. The purpose of this patent and literature review is to advocate the current management of acute skin reaction.

The Effect of Dietary Habits and Socioeconomic Status on the Prevalence of Iron Deficiency in Children of Northern Greece

Backround: Despite encouraging reports concerning the declining prevalence of iron deficiency, this easily preventable disorder is still an existing problem in presumably developed regions. Objective: To evaluate the prevalence of iron deficiency and relevant anemia in children residing in Northern Greece and to study possible associations. Design: 3,100 children aged 8 months to 15 years were evaluated. Socioeconomic status was determined based on the parents’ profession and place of residence. Nutrition habits were also evaluated. Results: The incidence of iron deficiency was found to be 14% and that of iron deficiency anemia was 2.9%, with a higher prevalence in children younger than 2 years of age. The place of residence was the most significant factor in relation to the development of iron depletion in the children studied. Additional independent factors were revealed to be breast-feeding, meat-containing meal consumption and the consumption of non-home-cooked meals. Conclusion: Iron deficiency remains prevalent in Northern Greece, mainly affecting the vulnerable toddler group. Nutritional iron deficiency is still a severe public health problem even in what are considered to be developed regions. An improvement of dietary habits and an upgrading of semiurban areas should contribute substantially to decreasing the prevalence of iron depletion in Greek children.