A clinical overview of carcinoid tumors: perspectives for improvement in treatment using peptide analogs (review)

Carcinoid tumors were first described more than a century ago, but the treatment of patients with advanced disease remains a challenge to physicians. The etiology of carcinoid tumors, the biologic determinants of the growth of these malignancies, as well as the high frequency of multiple carcinoid and/or non-carcinoid tumors in patients with this disease also remain to be elucidated. A 5-decade analysis of 13,715 carcinoid tumors in the USA showed that distant metastases were demonstrated at the time of diagnosis in 12.9% of patients with this neoplasia. The overall 5-year survival rate for all patients with carcinoids regardless of the site, was reported to be 67.2%. The prognosis of patients with early stage disease is good and surgical resection is the standard form of treatment. The resection of local or regional metastases can result in cure for some cases. However, patients with metastatic dissemination have poor outcomes since chemotherapy is generally ineffective. Surgical resection of isolated hepatic metastases, surgical hepatic artery ligation or embolization produce responses in selected patients. Radiation therapy may ease the pain of bone metastases. The administration of long acting analogs of somatostatin can control the symptoms of diarrhea and flushing in patients with the malignant carcinoid syndrome. However, a complete regression of metastatic carcinoid tumors following the administration of somatostatin analog octreotide has been reported so far in only 3 cases. Other modalities of treatment, including liver transplantation and the administration of radiolabeled somatostatin analogs have likewise been applied in patients with advanced disease. It is expected that advances in proteomics research will contribute to our understanding of the mechanisms of diseases and aid in designing new drugs

Rational use of agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH) in the treatment of hormone-sensitive neoplasms and gynaecologic conditions

Analogues of luteinizing hormone-releasing hormone (LH-RH) have made possible new approaches to the treatment of some hormone-dependent cancers and diseases and conditions which result from inappropriate sex hormone levels. In the fields of both gynaecology and oncology, the development of sustained delivery depot systems has played a key role in the clinical use of LH-RH agonists and will be also essential for the LH-RH antagonists. Clinical results show that therapy with agonists of LH-RH is the preferred method of treatment for men with advanced prostate cancer. For prostate cancer and other indications, the new LH-RH antagonists such as Cetrorelix may offer an advantage based on the fact that they inhibit LH, FSH and sex-steroid secretion from the start of the administration and thus reduce the time of the onset of therapeutic effects. The use of antagonists would avoid the temporary clinical “flare-up” of the disease which can occur with the agonists in men with prostate cancer. The rapid shrinkage of the prostate and improvement in urinary symptoms obtained with Cetrorelix in men with benign prostatic hyperplasia (BHP) suggests that LH-RH antagonists offer a therapeutic alternative in patients who are considered poor surgical risks. Various experimental and clinical studies suggest that analogues of LH-RH might be useful for treatment of premenopausal women with oestrogen-dependent breast cancer. LH-RH antagonists such as Cetrorelix could be also considered for hormonal therapy of epithelial ovarian cancer which responds only marginally to the agonists, and for treatment of endometrial cancer. Many investigators have reported beneficial effects of LH-RH agonists in the treatment of patients with leiomyomas. LH-RH antagonists also appear to be promising for therapy of uterine leiomyomas, and in addition might be useful for treatment of endometriosis and polycystic ovarian disease (PCOD). LH-RH agonists have been employed in in vitro fertilization and embryo transfer (IVF-ET) programs to prevent a premature rise in LH and various results suggest that the use of antagonist Cetrorelix in assisted reproduction procedures, could be even more advantageous. For most of these indications, the use of sustained release depot preparations will be required