Clinical prostate cancer最新文献

Background

Antigen-presenting cells 8015 (APC8015; Provenge®) is an immunotherapeutic product designed to initiate a T-cell–mediated immune response against prostatic acid phosphatase, an antigen overexpressed in 95% of prostate cancer cells. In phase I/II trials, APC8015 has shown immunologic and clinical responses in patients with androgen- independent prostate cancer. This phase II trial was conducted to assess the prostate-specific antigen (PSA)–modulating effects of APC8015 in patients with androgen-dependent prostate cancer (ADPC) with biochemical progression.

Patients and Methods

Patients with nonmetastatic recurrent disease as manifested by increasing PSA levels (0.4-6.0 ng/mL) and who had undergone previous definitive surgical or radiation therapy were enrolled. Therapy consisted of APC8015 infusion on weeks 0, 2, and 4 (ie, 3 infusions). Prostate-specific antigen was measured at baseline and monthly until disease progression, defined as a doubling of the baseline or nadir PSA value (whichever was lower) to ≥ 4 ng/mL or development of distant metastases.

Results

Thirteen of 18 patients demonstrated an increase in PSA doubling time (PSADT), with a median increase of 62% (4.9 months before treatment vs. 7.9 months after treatment; P = 0.09; signed-rank test).

Conclusion

Therapy was well tolerated. APC8015 as single-agent immunotherapy for patients with ADPC and biochemical progression did not result in ≥ 50% decrease in PSA from baseline levels but did appear to modulate PSADT in some patients. Further manipulations of host immunity may be required to achieve a significant antitumor effect.

In the vast majority of cases, cancer continues to be an incurable disease when it has spread beyond the primary organ. Most cancer research and therapy design to date has focused on chemotherapy directed at killing the replicating tumor cells. Little attention has been placed on targeting the microenvironments of the primary tumor site, the circulating tumor cells, or the metastatic or secondary (target) tumor site and how cancer cells move among them. To develop these targets, a better understanding of metastasis and the mechanisms underlying the spread of tumors is required. This review describes the steps of metastasis using a paradigm of emigration to migration to immigration, with prostate cancer as a model system.

The primary objective of this overview is to apprise clinical urologists and oncologists of the current state of fused multimodality imaging of prostate cancer, which can be applied to optimize treatment by ensuring that a patient's disease is characterized as well as current imaging technology permits. The focus of this study is the monoclonal antibody capromab pendetide, which targets prostate specific membrane antigen (PSMA), a type II membrane glycoprotein strongly associated with prostate cancer. Identifying where capromab pendetide uptake occurs can be done accurately if this functional imaging modality is combined with a modality that provides anatomic detail, such as computed tomography (CT) or magnetic resonance imaging (MRI). Image fusion, or coregistration, which is overlaying the functional images of capromab pendetide uptake on the anatomic CT or MRI images, provides a detailed map of cancer localization inside and outside the prostate gland. This same principle of fusing functional images on anatomic images is the basis for enormous growth of positron emission tomography with CT during the past 2 years. Positron emission tomography imaging has a different functionality base than does capromab pendetide, and thus the 2 modalities should be complementary. However, the key to both functional imaging modalities is accurate fusion with anatomic images, which is illustrated in our case reports. The cases cited demonstrate the need to optimize every phase of imaging from patient preparation to reading and reporting increased PSMA concentration seen on the fused images. Reference is also made to applying capromab pendetide/CT fused imaging to radiation therapy planning.

Prostate cancer is the most common nondermatologic malignancy in men. Prostate cancer is characterized by clinical and biologic heterogeneity that has complicated molecular and epidemiologic studies. Like other epithelial malignancies, prostate tumors exhibit complex karyotypic abnormalities and harbor many specific genetic alterations. Although recent work has begun to elucidate many of the specific mutations associated with prostate cancer, we still lack a clear understanding of the complement of genetic changes that suffice to program the malignant state. Here, we review our current understanding of the genetic changes found in prostate cancer and explore the connections between specific genetic alterations and malignant phenotypes including cell growth, survival, invasion, and metastasis.

There is a growing need to understand how nutritional and lifestyle practices may optimize quality of life (QOL) and health after diagnosis for the 1.5 million men living with prostate cancer in the United States. We are establishing a clinical cohort of men with prostate cancer at the University of California San Francisco. Men completed detailed dietary and lifestyle questionnaires annually and provided consent for blood and tissue specimens to be stored for research if they underwent radical prostatectomy. We examined the feasibility of establishing this cohort and analyzed preliminary baseline data on participant demographics, lifestyle habits, and QOL using χ² and t-tests and logistic regression models. Between February 2002 and July 2004, we enrolled 343 men with prostate cancer into the survey portion of this cohort. The response rate was approximately 85% via in-clinic enrollment and 30% via mail enrollment. Based on analysis of the first 193 men enrolled, there was a high level of treatment satisfaction in this population (88% of men were satisfied or extremely satisfied with treatment) and positive reports of general health perception (73% of men perceived themselves to be in excellent [34%] or very good [39%] health). Whether treatment interfered with diet was an independent predictor of health perception and treatment satisfaction. Use of dietary supplements was high (90%) in this well-educated population. In conclusion, we demonstrated good feasibility for conducting this longitudinal study and observed initial indications that diet and other lifestyle practices were important predictors of patient QOL.