Biomedical subjects

Robert J Amato

Publications and source records attributed to Robert J Amato.

7 recordsLinked to original sources

PubMed2003

Thalidomide therapy for renal cell carcinoma.

PURPOSE: To review the use of thalidomide as a therapeutic option for patients with metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: Studies of thalidomide alone or in combination with immunotherapy or chemotherapy were identified. The clinical benefit of thalidomide was assessed on the basis of objective response (complete and partial) and stable disease rates. RESULTS: Single-agent thalidomide was evaluated in nine phase II studies, producing partial responses in a median of 7% of patients (range: 0-17%) and stable disease in a median of 31% of patients. On average, 40-45% of patients derived benefit from thalidomide. Common toxicities included constipation, lethargy, and with prolonged therapy, neuropathy. Four studies reported deep vein thrombosis and/or pulmonary embolism at rates ranging from 3 to 23%. On the basis of these findings, phase I/II studies of thalidomide in combination with interleukin-2 (IL-2), interferon (IFN), or chemotherapy have been conducted. Although some of these early combination regimens were limited by toxicity, promising findings have been seen with thalidomide/IL-2 and thalidomide/IFN/capecitabine. A phase III trial of IFN versus IFN/thalidomide is nearing completion. CONCLUSION: Thalidomide is active in metastatic RCC, but additional experience with thalidomide-based combinations is needed to better define how this agent should be used in the management of this malignancy.

Angiogenesis Inhibitors↗

PubMed2003

Therapeutic targets for metastatic prostate cancer.

Prostate cancer is the most commonly diagnosed non-cutaneous cancer in adult males. Although prostate cancer that is confined to the gland can be cured in many patients using surgery or radiation, these treatments are only effective for localized tumors and the long-term failure rates for these treatments suggests that prostate cancer can metastasize relatively early in the course of the disease. Once prostate cancer has metastasized there are no curative therapies. The greatest challenge in the treatment of advanced prostate cancer is to access and eliminate metastatic cells. Therefore, effective prostate cancer therapy will require novel strategies to target cancer cells both at the site of the primary tumor and at distant metastatic sites. In this article we review several therapeutic targets and approaches that may provide new treatments for metastatic prostate cancer. We discuss the use of small molecules to target specific molecular events associated with metastatic prostate cancer, the use of specific antibodies that target unique metastasis associated molecules and the use of various gene therapy strategies to achieve anti-metastatic activities.

Animals↗

PubMed2002

Bilateral testicular germ cell tumors: twenty-year experience at M. D. Anderson Cancer Center.

BACKGROUND: The incidence of testicular carcinoma in the United States has increased significantly over the last two decades. Germ cell tumors form the majority of malignant testicular tumors. With advances in diagnosis and therapeutic approaches, germ cell tumors are now highly sensitive to treatment, providing long-term survival. It has been speculated that the incidence of bilateral germ cell tumors may increase due to the improved survival of patients with unilateral germ cell tumors. In this report, the authors present a study of bilateral germ cell tumors of the testis in men who were treated at The University of Texas M. D. Anderson Cancer Center over a 20-year period with emphasis on their incidence, histologic features, and clinical features. METHODS: Between 1978 and 1999, 2431 patients with testicular germ cell tumors were treated at The University of Texas M. D. Anderson Cancer Center. Among these, 24 patients with bilateral germ cell tumors were identified. Clinical records and all available pathology slides of the tumors were reviewed. RESULTS: The overall incidence of bilateral germ cell tumors in the patients with testicular germ cell tumors was 1% (24 of 2431 patients). The incidence was 1.8% (14 of 776 patients) in patients with seminoma and 0.6% (10 of 1655 patients) in patients with nonseminomatous germ cell tumors. Patients with seminoma who were age </= 30 years at the time of initial diagnosis had a higher incidence of bilateral tumors compared with older men. Twenty of 24 patients with bilateral germ cell tumors had metachronous tumors, and 4 patients had synchronous tumors. Among the patients with metachronous tumors, 70% of second tumors occurred within 5 years; the longest interval between the first and second tumors was 15 years. The outcome of patients with bilateral germ cell tumors was excellent; only 1 of 24 patients died of metastatic disease. CONCLUSIONS: The overall incidence of bilateral testicular germ cell tumors was 1% in patients who were treated at The University of Texas M. D. Anderson Cancer Center over the past two decades. The incidence of bilateral germ cell tumors was related to the histologic type of the initial tumor and to the patient's age at initial presentation in patients with seminoma. Thus, patients in the second or third decade of life who presented with seminomas as their initial tumor were more likely to develop a second germ cell tumor compared with patients in the fourth or fifth decade of life. These findings have potentially important implications for clinical management by identifying a population of patients with germ cell tumors who are at risk of developing a second tumor and also for studying risk factors of bilateral germ cell tumors of the testis.

Adolescent↗

PubMed2002

Thalidomide: an antineoplastic agent.

It has been more than three decades since the withdrawal of thalidomide from the marketplace. Thalidomide is attracting growing interest because of its reported immunomodulatory and anti-inflammatory properties. Current evidence indicates that thalidomide reduces the activity of the inflammatory cytokine tumor necrosis factor-alpha by accelerating the degradation of its messenger RNA. Thalidomide inhibits angiogenesis. Recently, thalidomide was approved for sale in the United States for the treatment of erythema nodosum leprosum, an inflammatory complication of Hansen's disease. Thalidomide has been used successfully in several other dermatologic disorders, including aphthous stomatitis, Behcet's syndrome, chronic cutaneous systemic lupus erythematosus, and graft-versus-host disease, the apparent shared characteristic of which is immune dysregulation. Many recent studies have evaluated thalidomide in patients with HIV infection, in which this drug is an efficacious agent against oral aphthous ulcers, HIV-associated wasting syndrome, HIV-related diarrhea, and Kaposi's sarcoma. Only in the last several years has thalidomide been aggressively investigated for its antiangiogenic potential and immunomodulatory properties in various tumor types. Current research on thalidomide in oncology covers investigation in a wide range of both solid tumors and hematologic malignancies.

Angiogenesis Inhibitors↗

PubMed2002

The role of caveolin-1 in androgen insensitive prostate cancer.

PURPOSE: We summarize the literature regarding androgen insensitive prostate cancer and caveolin-1. Caveolin-1 is a major structural component of caveolae, membrane micro-domains known to have important roles in signal transduction and lipid transport. MATERIALS AND METHODS: A review of the literature relevant to androgen insensitive caveolin-1 and prostate cancer included the first published report in 1998 through those published in March 2002. RESULTS: Caveolin-1 expression is increased in primary and metastatic human prostate cancer with highest levels observed after androgen ablation therapy. Recent studies have documented that caveolin-1 is secreted by prostate cancer cells and can be detected in the serum of men with prostate cancer. CONCLUSIONS: The results presented in this review establish that caveolin-1 is an autocrine/paracrine factor associated with androgen insensitive prostate cancer. They show the potential for caveolin-1 as a biomarker therapeutic target for this important malignancy.

Animals↗

PubMed2002

Irofulven, a novel inhibitor of DNA synthesis, in metastatic renal cell cancer.

Irofulven (6-Hydroxymethylacylfulvene, MGI-114) is the first of a new class of anticancer compounds the acylfulvenes which are derived from the natural product, illudin S. Irofulven is a potent anticancer agent with activity against a broad range of human tumors in vitro and in vivo. Irofulven covalently binds to DNA, inhibits DNA synthesis and induces apoptosis. Clinical activity has been observed in phase I studies. Because disease stabilizations were observed in kidney cancer patients in the phase I trials, we performed a phase II trial of irofulven in this patient population. Twenty patients were accrued. Irofulven (11 milligrams per meter squared per day) was administered as a 5 minute intravenous infusion for 5 consecutive days, and response was evaluated every 8 weeks. There were no objective responses. The most common toxicities were nausea, emesis, and thrombocytopenia. Irofulven, at the dose and schedule administered in this trial, showed no effect in metastatic renal cell cancer.

Adult↗

PubMedDate not supplied

Quality of life in patients with metastatic renal cell carcinoma participating in a phase I trial of an autologous tumor-derived vaccine.

BACKGROUND: We prospectively examined quality of life (QOL) in patients with metastatic renal cell carcinoma treated with nephrectomy followed by heat shock protein peptide complex 96 (HSPPC-96) vaccine, a nontoxic, active, specific immunotherapy. MATERIALS AND METHODS: QOL and intrusive thoughts were measured in 36 patients with newly diagnosed stage IV renal cell carcinoma at the start of treatment, 3 weeks later on the final day of treatment, and at follow-up 1 month later. At each assessment, patients completed the RAND 36-Item Health Survey and the Impact of Event Scale (IES). RESULTS: Mixed model analyses revealed a significant improvement over time in the Physical Component Summary score (p < 0.0001) and no significant change over time in the Mental Component Summary score or the IES scores. In comparisons with other populations, at the 1-month follow-up assessment, patients reported significantly worse QOL than the general population on the physical dimensions and similar QOL on the psychosocial and emotional dimensions, a similar QOL to that in patients with type II diabetes, and a significantly better QOL on four dimensions than that in patients with congestive heart failure. CONCLUSION: QOL remained stable or improved during treatment with the HSPPC-96 vaccine.

Attitude to Health↗