Catálogo de publicaciones - libros

Nanoparticles may serve, among other techniques, as a useful tool for achieving the main objective of regional cancer therapy: they can deliver a higher concentration of the agent to the tumor and expose the tumor to active drug for longer periods than safely possible with conventional formulations. These carriers combine many advantages, such as a potential for selective targeting and an opportunity to tailor particles with the desired characteristics offered by the versatility of polymer chemistry. This chapter describes the key issues of this research strategy relevant to the chemotherapy of cancer and provides an update on some novel targeting approaches.

Cancer is an important problem in public health worldwide. Gene therapy has the potential for improved treatment of cancer patients, particularly if used in combination with other, conventional therapies. To date, many strategies of gene therapy have been explored, including correction of mutant genes, immunstimulation, prodrug activation, interference of oncogene expression, and genetically modified oncolytic viruses. Although the preclinical results of gene therapy have shown promise for some cancers, cancer gene therapy is still at an early stage of clinical development and has not yet shown a significant therapeutic benefit for patients. The main obstacles to the introduction of gene therapy for patients are poor selectivity in vector targeting, inefficient gene transfer, and great difficulties in systemic application. Owing to the complex nature of targeted vector delivery to the tumor, strategies for gene therapy have focused their efforts on the development of local gene transfer to treat tumors locally for the benefit of the patient. This is not the answer for the treatment of a metastasizing systemic disease; however, it represents an important step toward the clinical applicability of cancer gene therapy. Furthermore, local control of tumor growth and progression could contribute to better control of the disease and improved quality of life for the patient.

The rationale for hepatic arterial infusion of chemotherapy is based on the concept that most primary and metastatic liver tumors preferentially derive their blood supply from the hepatic artery, whereas normal hepatic tissue relies on the portal venous blood supply. In addition, the ability of the hepatic parenchyma to metabolize chemotherapy drugs to nontoxic metabolites offers a unique opportunity to administer highly toxic drug levels to tumor cells while minimizing systemic toxicity. Regional chemotherapy has been evaluated in both primary and metastatic hepatic malignancies with varying results. The area of most intensive research has been in the treatment of colorectal cancer because it represents the most frequent etiology of hepatic metastases. Although the response rate with newer agents used in systemic combination chemotherapy has improved, the 2-year survival is only 25 to 39%. Hepatic-arterial infusion of chemotherapy produces higher response rates, with a 2-yr survival of 50 to 60%. In patients who can undergo liver resection followed by hepatic-arterial infusion, the 2-yr survival is 85%. This chapter summarizes the pharmacological basis and technical aspects of hepatic arterial infusion, including catheter placement, infusion regimens, and the development and treatment of unique toxicities. In addition, it will review the current evidence and role of hepatic arterial infusion for all primary and secondary hepatic malignancies, with a focus on liver metastases from colorectal cancer, as this is the area of most experience and promise.

Focal ablative techniques are promising tools in the treatment of unresectable primary and secondary liver tumors. Despite a lack of randomized controlled trials, early data suggest that these methods are effective and well-tolerated, with an acceptable complication rate. This chapter, an overview of established and experimental ablative methods, as well as clinical results reported thus far.

Carcinomatosis has been in the past a universally fatal manifestation of gastrointestinal cancer. It has also carried a nearly lethal prognosis in ovarian cancer. It remains the major site of treatment failure with these diseases. A review of the natural history of carcinomatosis from the world literature was undertaken. The rationale, technology, and results of treatment using peritonectomy and perioperative intraperitoneal chemotherapy represents an essential part of the treatment. Small-volume residual disease must be treatedby chemotherapy and hyperthermia. To apply these treatments properly, selection of patients using prognostic indicators is necessary. The results of treating patients who have peritoneal mesothelioma, pseudomyxoma peritonei, and carcinomatosis from colorectal cancer indicate that progress in the curative management of carcinomatosis has been made. Peritoneal surface dissemination of cancer can no longer be equated with a terminal condition. A multidisciplinary approach to treatment employing surgery and regional chemotherapy has created a new standard of care for this pattern of cancer dissemination.

Malignant peritoneal mesothelioma (MPM) is an incurable disease. It represents approximately 15% of all mesotheliomas and has a male predominance. It has a known relationship to asbestos, but most patients present with no known history of exposure. Simian virus 40 (SV40) exposure is potentially another risk factor, although the relationship is not entirely supported. Patients usually present with vague symptoms. Diagnosis is usually made on the basis of a CT scan and percutaneous or open biopsy. The disease remains confined to the abdominal cavity until very late in the disease course. Ascites is a frequent sign; morbidity and mortality are usually a consequence of disease progression within the abdominal cavity. Systemic chemotherapy and radiation have not yet been shown to have much influence over the natural history of the disease. In selected patients, surgical cytoreduction with intraoperative hyperfhermic peritoneal chemotherapy is associated with long-term survival. A summary of clinical experience with surgical cytoreduction and intraoperative intraperitoneal chemotherapy for MPM is presented.

Pancreatic cancer is a major cause of cancer death. Despite impressive advances in early hospital mortality and morbidity rates, overall, the chance of long-term survival is extremely low. Surgical treatment is currently the only potentially curative strategy for pancreatic cancer, but surgery alone cannot guarantee a cure. Regional therapy, such as regional chemotherapy or radiation, has been widely used in patients with advanced pancreatic cancer, with some success in controlling the cancer locally. The rationale for regional chemotherapy of pancreatic cancer is to enhance cellular drug uptake. There are various techniques of regional therapy, such as chemoembolization, arterial or portal venous infusion, hyperthermia, radiation, and gene therapy. This article reviews English reports of regional therapy for pancreatic cancer cited in the Medline database of Pubmed up to July 2005.

Advances in technology and the increase in screening for breast cancer that identifies tumors at earlier stages have made it possible to destroy tumors in situ without surgery. This can also be used to treat locally advanced tumors. These locoregional ablative techniques include minimally invasive surgical as well as noninvasive ablative modalities, new radiation technologies, and regional chemotherapy. New developments in imaging modalities such as MR make these treatment opportunities more precise and reliable. The regional minimally invasive technologies provide treatment options that are physiologically, cosmetically, and psychologically more acceptable to the patient. Many of these need further investigation before they become an accepted sound practice. This paper reviews and discusses the up-to-date data and feasibility of technologies for locoregional treatment of breast cancer

Advanced epithelial ovarian cancer (EOC) is an aggressive disease that remains and progresses inside the peritoneal cavity for most of its natural history. Despite the initial relative sensibility to first-line chemotherapy, most patients relapse and ultimately die of chemoresistant disease. The best second treatment option for recurrent disease has not been defined thus far. Secondary cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal chemotherapy (HIPEC) seems to constitute a possible second-line treatment option based on the results of phase II studies. A prospective randomized study testing the effectiveness of CRS + HIPEC in EOC is ongoing and the future prospects should aim at the refinement of its indications.

The urinary bladder is an ideal organ for local topical treament. Numerous agents have been instilled intravesically during the last century to decrease bladder tumor recurrence and prevent progression and subsequent patient mortality. Today, intravesical immunotherapy with BCG and chemotherapy are routinely used as an adjunct to surgical resection of superficial bladder tumors. Photodynamic therapy with different photosensitizers and thermotherapy in combination with intravesical chemotherapy or percutaneous radiotherapy have been evaluated in phase III studies and may soon be widely available tools for the clinical treatment of bladder cancer. The first clinical phase I trials demonstrating safe application have been reported for intravesical gene therapy and antisense therapy approaches. Despite initial promising results of HIFU therapy and interventional radiotherapy, it cannot be anticipated that these two techniques will enter the clinical routine in the near future. Although the bladder is an easily accessible organ for regional treatment, a glycosaminoglycan (GAG) layer on the bladder mucosa can prevent the sufficient uptake and integration of many intravesically applied therapeutical compounds. Iontophoresis has shown clinical success in enhancing the uptake of, for instance, chemotherapeutic agents. Furthermore, magnetically targeted carriers, microspheres, and nanocarriers have been tested preclinically.