Metastatic Testicular Germ Cell Cancer Research Articles

785P Thromboembolic events (TE) during treatment with cisplatin-based chemotherapy (CBCT) in metastatic testicular germ-cell cancer (TC)

785P Thromboembolic events (TE) during treatment with cisplatin-based chemotherapy (CBCT) in metastatic testicular germ-cell cancer (TC)

Evaluation of Chemotherapeutic Drugs for Treatment of (Cisplatin-Resistant) Germ Cell Cancer Cell Lines.

Cisplatin resistance still remains a major obstacle in the standard chemotherapeutic approach in late-stage and metastatic testicular germ cell cancer (GCC) patients. This multifactorial and complex phenomenon arises (concomitantly) on several levels due to impaired transport, decreased adduct formation, increased DNA-repair, decreased apoptosis, or compensating pathways. Evaluation of novel therapeutic approaches and pharmacological inhibitors still remains necessary to treat cisplatin-resistant GCCs. In this chapter, we present in vitro techniques to measure cytotoxic impacts of chemotherapeutic drugs on GCC cell lines. Specifically, we will discuss the measurement of relative cell viability by XTT assay, as well as cell cycle distribution and apoptosis assay by Nicoletti- and Annexin V/PI apoptosis assay with subsequent flow cytometry, respectively, to evaluate the effects of cytotoxic treatment in GCC cell lines.

High dose chemotherapy with stem cell support in the treatment of testicular cancer.

Testicular germ cell cancer (TGCC) is rare form of malignant disease that occurs mostly in young man between age 15 and 40. The worldwide incidence of TGCC is 1.5 per 100000 man with the highest rates in North Europe. After discovery of cisplatin cure rates of TGCC are very favorable between 90%-95% and unlike most solid tumors, cure rate for metastatic TGCC is around 80%. Metastatic TGCC is usually treated with 3-4 cycles of bleomycin, etoposide, cisplatinum chemotherapy with or without retroperitoneal surgery and cure rates with this approach are between 41% in poor risk group and 92% in good risk group of patients. Cure rates are lower in relapsed and refractory patients and many of them will die from the disease if not cured with first line chemotherapy. High dose chemotherapy (HDCT) approach was used for the first time during the 1980s. Progress in hematology allowed the possibility to keep autologous haematopoietic stem cells alive ex-vivo at very low temperatures and use them to repopulate the bone marrow after sub-lethal dose of intesive myeloablative chemotherapy. Despite the fact that there is no positive randomized study to prove HDCT concept, cure rates in relapsed TGCC are higher after high dose therapy then in historical controls in studies with conventional treatment. Here we review clinical studies in HDCT for TGCC, possibilities of mobilising sufficient number of stem cells and future directions in the treatment of this disease.

Current status of chemotherapy in risk‐adapted management for metastatic testicular germ cell cancer

Today, approximately 80% of men with metastatic testicular cancer can be cured with chemotherapy combined with the appropriate surgery. The improved treatment outcome has led to the stratification of patients with metastatic disease by the consensus prognostic index; the International Germ Cell Cancer Consensus Group classification. Currently, the first-line chemotherapy with bleomycin, etoposide, and cisplatin (BEP) remains the standard management of metastatic testicular cancer. Three cycles of BEP for good-prognosis patients and four cycles of BEP for intermediate- and poor-prognosis patients are the standard first-line chemotherapy. To achieve the optimal outcome, BEP should be given with appropriate supportive care and risk assessment for toxicity. Although no universal prognostic criteria have been defined for the recurrent or refractory disease, the risk-adapted approach may clarify the role of ifosfamide- and paclitaxel-containing conventional-dose chemotherapy or high-dose chemotherapy in the second-line setting. Several investigators reported recent improvement of treatment outcome of testicular cancer patients, especially those with poor prognosis. Along with the progress in chemotherapy, the risk-adapted management at experienced hospitals seems to be responsible for the recent progress in treatment outcome.

Small bowel obstruction caused by secondary tumors

Small bowel obstruction in an oncology patient is a common and serious medical problem which is associated with diagnostic as well as therapeutic dilemmas. While the condition is most commonly caused by postoperative adhesions and peritoneal carcinomatosis, other causes have been reported [Cormier WJ, Gaffey TA, Welch JM, et al. Linitis plastica caused by metastatic lobular carcinoma of the breast. Mayo Clinical Proceedings 1980;55:747-53; Clavien P-A, Laffer U, Torhos J, et al. Gastrointestinal metastases as first clinical manifestation of the dissemination of a breast cancer. European Journal of Surgical Oncology 1990;16:121-6; Bender GN, Maglinte DD, McLarney JH, et al. Malignant melanoma: patterns of metastasis to the small bowel, reliability of imaging studies, and clinical relevance. American Journal of Gastroenterology 2001;96:2392-400; Gatsoulis N, Roukounakis N, Kafetzis I, et al. Small bowel intussusception due to metastatic malignant melanoma. A case report. Technical Coloproctology 2004;8:141-3; Hung GY, Chiou T, Hsieh YL, et al. Intestinal metastasis causing intussusception in a patient treated for osteosarcoma with history of multiple metastases: a case report. Japanese Journal of Clinical Oncology 2001;31(4):165-7; Chen TF, Eardley I, Doyle PT, Bullock KN. Rectal obstruction secondary to carcinoma of the prostate treated by transanal resection of the prostate. British Journal of Urology 1992;70(6):643-7; Kamal HS, Farah RE, Hamzi HA, et al. Unusual presentation of rectal adenocarcinoma. Roman Journal of Gastroenterology 2003;12(1):47-50; Hofflander R, Beckes D, Kapre S, et al. A case of jejunal intussusception with gastrointestinal bleeding caused by metastatic testicular germ cell cancer. Digestive Surgery 1999;16(5):439-40]. One of these, reported thus far in only very few patients, is obstruction caused by secondary tumors, i.e. metastases from other organs to the small bowel wall. As cancer patients live longer with improved therapy, physicians are more likely to cope with rare phenomena of neoplasms, such as small bowel obstruction caused by secondary tumors. We hereby present a review of the relevant medical literature. The goal of this article is to define current knowledge on this phenomenon, with emphasis on its epidemiology and clinical characteristics, and to increase the awareness of the clinician treating cancer patients of such possibility.

Recent Developments in the Field of Anticancer Platinum Complexes

Cisplatin, carboplatin and oxaliplatin continue to be among the most efficient anticancer drugs in world-wide clinical use so far. In particular, cisplatin has shown a remarkable therapeutic efficacy in a broad spectrum of solid tumors and outstanding activity against metastatic testicular germ-cell cancer with cure rates of about 90% of cases. Nevertheless, the dose-limiting severe toxic side-effects of platinum-based chemotherapy, the problem of inherent or therapy-induced resistance, the limited activity in a range of tumors, and the meager tumor selectivity are the motivation for tremendous efforts and inventions in the development of novel anticancer platinum drugs. This article reviews the most recent patents in this field of research, covering the following strategies in the design of promising anticancer platinum complexes: (i) synthesis of new anticancer platinum complexes, using combinatorial chemistry and high throughput synthesis and screening, (ii) activation of platinum complexes in the tumor tissue, (iii) accumulation of platinum complexes at the tumor site, (iv) novel platinum complexes, displaying activity against cisplatin resistant cells and as inhibitors of specific biological functions, and (v) direct derivatives of classical anticancer platinum drugs in clinical use.

Orchidectomy after chemotherapy for patients with metastatic testicular germ cell cancer.

To evaluate the contribution of routine orchidectomy in the management of patients who present with advanced, metastatic, testicular germ cell cancer and who are treated with initial chemotherapy. Sixty consecutive patients presenting with metastatic testicular germ cell cancer and treated with initial chemotherapy followed by orchidectomy were identified. The results from a clinical and pathological review of these patients are presented. The pathological findings at orchidectomy were compared with the pathological findings from metastatic masses resected after chemotherapy, and are reviewed with the clinical outcome. Of the 60 orchidectomy specimens after chemotherapy, 24 (40%) contained significant histological abnormalities comprising residual invasive germ cell cancer, intratubular germ cell neoplasia and/or mature teratoma. The remaining 36 (60%) orchidectomy specimens contained fibrous scarring with or with no necrosis. Six (10%) orchidectomy specimens contained residual invasive germ cell cancer, three nonseminomatous germ cell cancer (NSGCT) and three seminoma. The patients with residual invasive NSGCT present within the testis had evidence of residual invasive NSGCT within extragonadal masses resected after chemotherapy; all three have relapsed and died from chemorefractory progressive disease. Orchidectomy after chemotherapy is recommended in all patients undergoing primary chemotherapy, as a significant proportion (40%) are left with histological abnormalities that predispose to subsequent relapse. Persistence of invasive NSGCT at the site of the primary tumour after chemotherapy is associated with persistence of invasive disease at other metastatic sites and is a poor prognostic finding.