Georgios V. Koukourakis

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.

Granulosa Cell Tumor of the Ovary: Tumor Review

Granulosa cell tumors of the ovary are rare neoplasms that originate from sex-cord stromal cells. The long natural history of granulosa cell tumors and their tendency to recur years after the initial diagnosis are the most prominent of their characteristics. The secretion of estradiol is the reason for signs at presentation such as vaginal bleeding and precocious puberty. Abdominal pain and hemoperitoneum, which occasionally can occur, are attributable to tumor rupture. The most common finding in pelvic examination is a tumor mass, which is subsequently confirmed with imaging techniques. Surgery is the mainstay of initial management for histological diagnosis, appropriate staging, and debulking. A more conservative unilateral salpingo-oophorectomy is indicated in patients with stage I disease and patients of reproductive age. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the appropriate surgical treatment for postmenopausal women and those with more advanced disease. The stage of disease is the most important prognostic factor associated with the risk of relapse. There are no clear conclusions regarding the role of postoperative chemotherapy or radiotherapy in stage I disease and in those with completely resected tumor. The use of adjuvant chemotherapy or radiotherapy has sometimes been associated with prolonged disease-free survival and possibly overall survival. Chemotherapy is the treatment of choice for patients with advanced, recurrent, or metastatic disease, and BEP (bleomycin, etoposide, and cisplatin) is the preferred regimen. Although the overall rate of response to treatment is high, the impact of treatment on disease-free or overall survival is unknown. Prolonged surveillance is mandatory because tumors tend to recur years after the initial diagnosis.

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.

Targeted therapy with bevacizumab (Avastin) for metastatic colorectal cancer.

During the last decade, the development of new drugs known as targeted therapies was the result of a better understanding of the processes involved in the transformation of normal cells into cancer. The term targeted therapy refers to drugs that selectively target specific molecular pathways involved in tumorigenesis or tumour progression. Angiogenesis is important for tumour growth and metastasis, and is an important target for new biological agents. Bevacizumab is a humanised recombinant antibody that prevents vascular endothelial growth factor (VEGF) receptor binding, and inhibits angiogenesis and tumour growth. On February 26, 2004, the Food and Drug Administration approved bevacizumab as first-line treatment for patients with metastatic colorectal cancer (CRC). The integration of targeted therapies in the treatment of colon cancer has resulted in significant improvements in efficacy outcomes. The efficacy of bevacizumab in the treatment of metastatic CRC is presented in this review article.

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.

Comprehensive Management of Upper Tract Urothelial Carcinoma

Urothelial carcinoma of the upper urinary tract represents only 5% of all urothelial cancers. The 5-year cancer-specific survival in the United States is roughly 75% with grade and stage being the most powerful predictors of survival. Nephroureterectomy with excision of the ipsilateral ureteral orifice and bladder cuff en bloc remains the gold standard treatment of the upper urinary tract urothelial cancers, while endoscopic and laparoscopic approaches are rapidly evolving as reasonable alternatives of care depending on grade and stage of disease. Several controversies remain in their management, including a selection of endoscopic versus laparoscopic approaches, management strategies on the distal ureter, the role of lymphadenectomy, and the value of chemotherapy in upper tract disease. Aims of this paper are to critically review the management of such tumors, including endoscopic management, laparoscopic nephroureterectomy and management of the distal ureter, the role of lymphadenectomy, and the emerging role of chemotherapy in their treatment.

Capecitabine for locally advanced and metastatic colorectal cancer: A review

Capecitabine (Xeloda(®)) is an oral fluoropyrimidine which is produced as a pro-drug of fluorouracil, and shows improved tolerability and intratumor drug concentrations following its tumor-specific conversion to the active drug. We have searched the Pubmed and Cochrane databases from 1980 to 2009 with the purpose of reviewing all available information on Capecitabine, focusing on its clinical effectiveness against colorectal cancer. Special attention has been paid to trials that compared Capecitabine with standard folinic acid (leucovorin, LV)-modulated intravenous 5-fluorouracil (5-FU) bolus regimens in patients with metastatic colorectal cancer. Moreover the efficacy of Capecitabine on metastatic colorectal cancer, either alone or in various combinations with other active drugs such as Irinotecan and Oxaliplatin was also assessed. Finally, neoadjuvant therapy consisting of Capecitabine plus radiation therapy, for locally advanced rectal cancer was analysed. This combination of chemotherapy and radiotherapy has a special role in tumor down staging and in sphincter preservation for lower rectal tumors. Comparative trials have shown that Capecitabine is at least equivalent to the standard LV-5-FU combination in relation to progression-free and overall survival whilst showing a better tolerability profile with a much lower incidence of stomatitis. It is now known that Capecitabine can be combined with other active drugs such as Irinotecan and Oxaliplatin. The combination of Oxaliplatin with Capecitabine represents a new standard of care for metastatic colorectal cancer. Combinating the Capecitabine-Oxaliplatin regimen with promising new biological drugs such as Bevacizumab seems to give a realistic prospect of further improvement in time to progression of metastatic disease. Moreover, preoperative chemo-radiation using oral capecitabine is better tolerated than bolus 5-FU and is more effective in the promotion of both down-staging and sphincter preservation in patients with locally advanced rectal cancer. Finally, the outcomes of recently published trials suggest that capecitabine seems to be more cost effective than other standard treatments for the management of patients with colorectal cancer.

Ameloblastoma, a rare benign odontogenic tumour: an interesting tumour review targeting the role of radiation therapy

Ameloblastoma is known as a benign, slowgrowing, rare, odontogenic neoplasm. The solid/multicystic, the unicystic with a fibrous connective-tissue capsule and the peripheral ameloblastoma represent the three well distinguished clinical types of ameloblastoma. Surgical resection with an attempt to achieve adequate free margins constitutes a well documented and accepted treatment modality. Controversies exist, however, with regard to the extent of operative intervention. Patients with inadequate or positive surgical margins or unresectable lesions can be treated with radiation or combined radiation and chemotherapy. The authors present a review of this sparse disease focusing on the special role and efficacy of radiation therapy in its management.

Lymphoma of the testis as primary location: tumour review.

Non-Hodgkin’s lymphoma as a primary testicular neoplasm accounts approximately 9% of all testicular malignant tumours and about 1–2% of all non-Hodgkin’s lymphoma. This neoplasm is the most common malignant tumour of the testis in the elderly. The most common histotype in primary forms is the diffuse large B-cell lymphoma, whereas more aggressive histologies such as Burkitt’s lymphoma are principal founded in cases of secondary involvement of the testis. Regarding clinical presentation, the most common sign is a unilateral painless scrotal swelling, sometimes with sharp scrotal pain or hydrocele. In patients with advanced stage, the systematic B symptoms are present in 25–41% of all cases. In 35% of patients, bilateral testicular involvement is detected. In more advanced stages with para-aortic lymph-node involvement, ascites and abdominal pain is evident. Despite the fact that responses to doxorubicin-containing chemotherapy, especially in early stages, show good results, relapses are often seen, and the prognosis of this tumour is very poor. Testicular lymphoma often disseminates to other extranodal organs, such as contralateral testis, central nervous system (CNS), lung, pleura, Waldeyer’s ring and soft tissue. For patients with limited disease, the recommended first-line treatment is orchiectomy followed by rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combination chemotherapy, with central nervous system (CNS) prophylaxis and prophylactic irradiation of the contralateral testis. In more advanced or relapsed disease, management should follow the worldwide recommendations for nodal diffuse large B-cell lymphoma (DLBCL). Here we present a review of this tumour.