An update of lanreotide acetate for treatment of adults with carcinoid syndrome.

Carcinoid tumors are rare and usually slow-growing. Some patients with advanced metastatic disease however can develop symptoms of carcinoid syndrome, which results in debilitating diarrhea and flushing. Many treatments including chemotherapy were tried unsuccessfully in the past to treat this syndrome. The symptoms of carcinoid syndrome are thought to be related to the ability of the tumors to produce serotonin. The discovery that the production of this hormone can be inhibited by somatostatin led to the development of somatostatin analogues octreotide and lanreotide, which differ from native somatostatin in that they have a longer half-life. These compounds have shown dramatic responses in symptom control and reduction of serotonin metabolites including urinary 5-hydroxyindoleacetic acid (5-HIAA) levels. This review researches the origins of carcinoid tumors, the development of lanreotide as a treatment and future directions for the treatment of carcinoid syndrome.

Olaratumab for the treatment of soft tissue sarcoma.

Soft tissue sarcoma represents about 1% of all solid malignancies. The standard chemotherapy regimens have included doxorubicin alone or in combination with other agents. Despite recent advances in treatment beyond first line - with the FDA approval of pazopanib, eribulin and trabectidin - overall survival for patients with metastatic disease remains in the region of 12-19 months. Olaratumab is a monoclonal antibody directed against platelet-derived growth factor receptor alpha (PDGFRalpha). It was studied in a phase Ib and randomized phase II study in combination with doxorubicin in patients with soft tissue sarcoma who previously had not received doxorubicin for metastatic disease. The results of the phase II study showed a statistically significant improvement in progression-free survival up to 6 months, and a more dramatic improvement in overall survival to 26.9 months. This is the first randomized trial to show a significant improvement in overall survival compared to doxorubicin alone. An ongoing phase III study has completed accrual and results are being analyzed. Olaratumab has been granted accelerated approval by the United States Food and Drug Administration. Ongoing trials are underway to further demonstrate the mechanism of action. This review will document the studies involved in the development of olaratumab in the treatment of soft tissue sarcomas.

Efficacy and tolerability of pharmacotherapy options for the treatment of medullary thyroid cancer.

Metastatic and unresectable medullary thyroid carcinoma (MTC) is often difficult to treat as it is relatively unresponsive to radiation and conventional chemotherapy. This emphasizes the importance of the development of targeted therapies for advanced MTC. Vandetanib was approved by the US Food and Drug Administration for the treatment of symptomatic or progressive MTC in patients with advanced disease in April 2011. This therapy proved to be a breakthrough in the management of MTC. We review the efficacy and safety of this novel treatment and other treatments that are being evaluated in this disease.

Anticipation in familial plasma cell dyscrasias.

Familial myeloma was described as early as 1925; however, the causative factors are unknown. Studies of families with other familial haematological malignancies demonstrate anticipation. Five new families are described in which plasma cell dyscrasias occurred in parent and child generations (six such pairs), and data were pooled with those of 16 other families (with 20 parent-child pairs affected) recorded in the literature. Disease-free survival for parent and child generations were each estimated and differences in the disease-free survival between generations were tested by the log-rank and signed rank methods. In all six previously unreported parent-child pairs with plasma cell dyscrasia and in 18/20 such pairs found in the literature, the disease occurred at an earlier age in the child generation. The median age of onset of myeloma in the parent and child generations of all 26 pairs was 71 years (95% CI 67-78 years) and 50 years (95% CI 45-55 years), respectively (P<0.0001). The ages of onset of malignant plasma cell dyscrasias in the parent and child generations of these families compared with patients in the general population were significantly different for the child generation (P<0.005) but not for the parent generation. It would appear that anticipation occurs in familial myeloma.