In small cell lung cancer, combination chemotherapy including agents such as etoposide, teniposide, cisplatin, doxorubicin, vincristine and cyclophosphamide continues to be the backbone of therapy. Epipodophyllotoxin derivatives, together with cisplatin, are used increasingly as part of the initial therapy. Complete plus partial responses to combination chemotherapy still occur in 80-90% of all patients with a median duration of 9-11 months. Median survival in these studies is at present 11-16 months depending on the initial tumour stage. Deaths from small cell lung cancer continue to occur until 7 years after diagnosis, but rarely thereafter. At this point, overall survival is around 5% and include a small fraction of patients (1%) initially presenting with extensive disease. The optimum duration of treatment is still uncertain. For patients with extensive disease, the use of alternating chemotherapy has been shown in a couple of randomized studies to yield the best results, as judged by long-term survival. The results of several phase II studies stress the importance of dose scheduling of etoposide in small cell lung cancer, with continuous treatment of 5 days' duration or more being superior. The therapeutic results for epidermoid, adenoid, large cell carcinoma and mesothelioma are essentially unchanged. The treatment of patients with these types of lung cancer should continue to be considered experimental, since no standard chemotherapy has as yet been developed, neither when given as single modality nor in combination with surgery or radiotherapy. One single study comparing induction chemotherapy before irradiation vs irradiation alone has resulted in an improvement of median survival of 4 months and doubled the number of long-term survivors. Since three-fourths of the patients with locoregional disease will die within 3 years, further improvements in both systemic and local treatment are needed.
This chapter covers the management of non-small cell lung cancer, small cell lung cancer, and mesothelioma. It covers the epidemiology and aetiology of each specific cancer. Common presenting signs and symptoms are described, as well as the normal investigative pathway. Management of the different stages of non-small cell and small cell lung cancer are covered, including surgery, chemotherapy, and radiotherapy, and for non-small cell lung cancer the targeted therapies. The section on mesothelioma looks at the aetiology, in particular the occupational and environmental aspect, including issues surrounding compensation and notification. Management of the disease includes surgery, chemotherapy, and radiotherapy. Nursing management issues that are covered include supporting patients with poor-prognosis disease and the complex psychosocial issues of this diagnosis.
Radiation Medicine Rounds is intended to serve as both a reference and instructional tool for students, housestaff, fellows, practicing clinicians, medical physicists, cancer biologists, radiobiologists, and interdisciplinary colleagues throughout the oncology spectrum. This issue of Radiation Medicine Rounds discusses the more salient topics surrounding the role of radiation therapy in breast cancer. The specialty of radiation therapy has increased in complexity over the years, yet as technology improves, the goal of improving outcomes while decreasing toxicity remains critical.
There is a markedly increased risk of Kaposi's sarcoma, non-Hodgkin's lymphoma (NHL) and invasive cervical cancer during the course of infection with the human immunodeficiency virus (HIV). Therapy for these acquired immunodeficiency syndrome (AIDS) defining illnesses first involves anti-retroviral therapy to suppress HIV viremia and maintain CD4 counts. Subsequent chemotherapy is complicated by the underlying immunoparesis and options in the management of all three diseases are discussed herein. Improved understanding of their aetiopathogenesis will hopefully delineate new therapeutic options and strategies to control viral replication and virally induced diseases including malignancy.
Radiation Medicine Rounds is intended to serve as both a reference and instructional tool for students, housestaff, fellows, practicing clinicians, medical physicists, cancer biologists, radiobiologists, and interdisciplinary colleagues throughout the oncology spectrum. This issue of Radiation Medicine Rounds discusses the more salient topics surrounding the role of radiation therapy in breast cancer. The specialty of radiation therapy has increased in complexity over the years, yet as technology improves, the goal of improving outcomes while decreasing toxicity remains critical.
This article reviews the mechanism of action, toxicity, pharmacology and clinical use of antineoplastic agents that inhibit the enzyme, topoisomerase II. Information presented in the medical and scientific literature in the past 3 years is especially highlighted.
The cell cycle represents a series of tightly integrated events that allow the cell to grow and proliferate. Critical parts of the cell cycle machinery are the cyclin dependent kinases (CDKs) which, when activated, provide a means for the cell to move from one phase of the cell cycle to the next. The CDKs are positively regulated by cyclins and negatively regulated by naturally occurring cyclin dependent kinase inhibitors (CDKIs). Cancer represents a dysregulation of the cell cycle such that cells that over-express cyclins or do not express the CDKIs continue to undergo unregulated cell growth. The cell cycle also serves to protect the cell from DNA damage. Thus, cell cycle arrest represents a survival mechanism that provides the tumor cell the opportunity to repair damaged DNA. Abrogation of cell cycle checkpoints before DNA repair is complete can activate the apoptotic cascade leading to cell death. Over the past several years a series of targeted agents have been developed that directly inhibit the CDKs, inhibit unrestricted cell growth, and induce a growth arrest. In addition, there are now agents that abrogate the cell cycle checkpoints at critical time points and make the tumor cell susceptible to apoptosis. Many of these agents are now in clinical trials and represent a new direction in cancer treatment. An understanding of the cell cycle is critical to learning how best to clinically develop these agents, both when administered as single agents or in combination with chemotherapy.
The field of Urology encompasses many diverse and divergent tumor histologies with ever-changing staging modalities and treatment algorithms. This review will focus on new developments for the major urologic malignancies including prostate, renal, bladder and testicular cancer, specifically looking at randomized, controlled studies published within the last academic year in peer-review journals.
The farnesyltransferase inhibitors (FTIs) were designed to inhibit the post-translational processing of Ras proteins, which are mutated in 30% of all human cancers. Recent studies suggest, however, that the target of FTIs may be a protein other than Ras, and that these agents may be more appropriately used to treat tumors with activated wild-type ras signaling. Preliminary results from several phase II and phase III studies have been reported. The FTIs fail to show significant single-agent activity in non-small cell lung cancer, small cell lung cancer, pancreatic cancer, refractory colorectal cancer, and bladder cancer. Activity has been shown in hematologic malignancies (acute myeloid leukemia, chronic myeloid leukemia, myelodysplastic syndrome), breast cancer, and glioma. Several combination studies of FTIs and standard cytotoxic agents are ongoing.
Drugs that target tubulin, including the vinca alkaloids and taxanes, represent some of the most effective anticancer medications. Both natural-product and semisynthetic compounds show a remarkable spectrum of anticancer activity. In this chapter, we review new developments in cancer biology and pharmacology that shed light on the effectiveness of tubulin binding agents. In addition, we highlight newer agents and several drugs in preclinical development that hold considerable promise for the future. Finally, we comment on the rational selection of patients for chemotherapy and a more mechanistic approach to using these drugs in combinations.
