Developments in drug delivery: implications for cancer care

Changes in drug delivery as well as new drug development have impacted on cancer care in the past twenty years. Several modified release chemicals now have a role in cancer care, and new routes of drug delivery have been established as part of standard care. A range of strategies has been investigated to enhance anti-tumor selectivity of drugs including antibodies, liposomes and carrier molecules homing or activated in the environment of tumors. Fixed drug combinations are also used in cancer supportive care, and may find use in a range of settings.     

Supporting the transformative process: experiences of cancer patients receiving integrative care

PURPOSE: The purpose of this study is to describe the essential features of the transformative experience among people living with cancer who are seeking integrative care and to identify factors supporting this process. It is hoped that after establishing the nature and meaning of this change or shift, one will better understand what is most meaningful in terms of providing appropriate care and support to patients seeking integrative care. STUDY DESIGN: An interpretational, qualitative approach guided sampling, data collection, and analysis with 11 individuals. A purposeful sample was drawn from selected integrative care facilities according to sociodemographics and type of cancer. Due to the complexity of this subject, second interviews were conducted with 5 participants to enhance the richness and validity of the data. RESULTS: The experience of transformation is a dynamic 4-stage process in which participants learned about themselves and became more aware of who they are and how they relate to the world. Participants found that 4 dimensions of integrative medicine played a fundamental role in supporting this process. These dimensions include (1) having access to a range of appropriate therapies to support individual journeys, (2) care that focuses on one's overall well-being, (3) control over cancer management, and (4) developing healing relationships with care providers. CONCLUSION: Although practitioners may not be able to create transformative experiences for patients, they may be able to establish and maintain conditions that support this process.     

The antioxidant effect of lovastatin on phagocyte-induced DNA damage: implications for cancer prevention

Lovastatin is one of a series of HMG-CoA reductase inhibitors used in the treatment of hypercholesterolemia. It may also inhibit atheroma formation by inhibiting the oxidation of low density lipoproteins (LDLs). We investigated the antioxidant properties of lovastatin and its effect on phagocyte-induced genotoxicity in mammalian cells. In a cytochrome c reduction assay using 106 phorbol ester-induced phagocytes as a positive control, lovastatin (10 microM) in its naturally occurring lactone form, had no effect. When converted to its acid form, however, superoxide anion formation was inhibted by 36%. Similarly, lovastatin in its acid form completely inhibited H2O2 formation by stimulated phagocytes. Using the fluorometric analysis of DNA unwinding, single-strand breakage was assayed in MRC-5 lung cells exposed to 106 human phagocytes +/- lovastatin (10 microM, 5 min. incubation). Stimulated phagocytes induced a decrease in double-stranded DNA to 48% of control values which, in the presence of lovastatin, reverted to 91% of control values. Lovastatin acts as an antioxidant by decreasing oxygen radical production by human phagocytes and may be important in abrogating the carcinogenic effect of chronic inflammation.     

Polygenic susceptibility to testicular cancer: implications for personalised health care

Background:

The increasing incidence of testicular germ cell tumour (TGCT) combined with its strong heritable basis suggests that stratified screening for the early detection of TGCT may be clinically useful. We modelled the efficiency of such a personalised screening approach, based on genetic risk profiling in combination with other diagnostic tools.

Methods:

We compared the number of cases potentially detectable in the population under a number of screening models. The polygenic risk scoring (PRS) model was assumed to have a log-normal relative risk distribution across the 19 currently known TGCT susceptibility variants. The diagnostic performance of testicular biopsy and non-invasive semen analysis was also assessed, within a simulated combined screening programme.

Results:

The area under the curve for the TGCT PRS model was 0.72 with individuals in the top 1% of the PRS having a nine-fold increased TGCT risk compared with the population median. Results from population-screening simulations only achieved a maximal positive predictive value (PPV) of 60%, highlighting broader clinical factors that challenge such strategies, not least the rare nature of TGCT. In terms of future improvements, heritability estimates suggest that a significant number of additional genetic risk factors for TGCT remain to be discovered, identification of which would potentially yield improvement of the PPV to 80–90%.

Conclusions:

While personalised screening models may offer enhanced TGCT risk discrimination, presently the case for population-level testing is not compelling. However, future advances, such as more routine generation of whole genome data is likely to alter the landscape. More targeted screening programs may plausibly then offer clinical benefit, particularly given the significant survivorship issues associated with the successful treatment of TGCT.     

Proteomics and ovarian cancer: implications for diagnosis and treatment: a critical review of the recent literature

PURPOSE OF REVIEW: Epithelial ovarian cancer is the leading cause of death from gynecologic malignancies amongst American women. Emerging proteomic technologies have promise for early diagnosis and in advancing treatment directions. Application of these technologies has produced new biomarkers, diagnostic approaches, and understanding of disease biology. RECENT FINDINGS: Mass spectral blood and tissue analysis has yielded new putative biomarkers that require further validation and assessment of diagnostic specificity and sensitivity. Protein signature patterns derived from mass spectrometry datastreams have been modeled and are moving into validation. Tissue-based protein analysis has led to identification of tumor and stromal protein and signal activation events in ovarian cancer. Clinical trials are now ascertaining tissue samples prior to and during therapy with molecularly targeted agents to evaluate modulation of targeted signaling pathways. Finally, proteomic analysis of tissues and metastases will outline biochemical events underlying the metastatic phenotype of ovarian cancer. SUMMARY: Proteomic approaches are experimental technologies applied to ovarian and other cancers. Proper validation and use of findings may advance our understanding of biochemical events that have complicated successful detection and intervention. This knowledge is the first step in fulfilling the promise of personalized molecular medicine.     

Using mixed methods for evaluating an integrative approach to cancer care: a case study

OBJECTIVE: To evaluate the impact of participating in an integrative cancer care program at the Centre for Integrated Healing in Vancouver, British Columbia, on patients' lifestyle, quality of life, and overall well-being. STUDY DESIGN: A mixed-methods case study with a pre- and posttest design. No control group was utilized. METHODS: All new patients starting at the Centre for Integrated Healing between May and September of 2004 were invited to join the study. Forty-six of 77 new patients agreed to participate. Quantitative data measuring quality of life, social support, anxiety and depression, locus of control, and hope were assessed at baseline (pre-program start) and at 6 weeks and 5 months from the start of the program. Qualitative data in the form of focus groups and interviews were collected midway through the follow-up period to further explore program impacts. RESULTS: No statistically significant improvements or declines were noted on the quantitative measures between baseline and the 5-month follow-up point. The qualitative findings revealed a theme of patients' active engagement in their cancer care involving empowered decision making and creating personal change. Facilitators of active patient engagement in their own care from the integrative program included healing partnerships with practitioners, information and resources, managing the integration of complementary and conventional therapies, emotional support, and a sense of hope. DISCUSSION: This case study was a first attempt at documenting the impact of an integrative cancer care program at the Centre for Integrated Healing. Study limitations included a small sample size, which limited power to detect quantitative changes on the questionnaires and a lack of a control group. Qualitative findings indicated that patients found value in the "person-oriented" holistic approach to care, which encouraged patients to take an active role in decision making and self-care. The use of a mixed-methods research design proved to be an effective approach to not only evaluating outcomes but also examining process issues of the experience. Additional research is greatly needed to better understand potential impacts of integrative approaches to cancer care.     

Understanding fragmentation of prostate cancer survivorship care: implications for cost and quality

BACKGROUND:

Cancer survivors are particularly prone to the effects of a fragmented health care delivery system. The implications of fragmented cancer care across providers likely include greater spending and worse quality of care. For this reason, the authors measured relations between increasing fragmentation of cancer care, expenditures, and quality of care among prostate cancer survivors.

METHODS:

A total of 67,736 patients diagnosed with prostate cancer between 1992 and 2005 were identified using Surveillance, Epidemiology, and End Results (SEER)‐Medicare data. Using the Herfindahl‐Hirschman Index and a measure of the average number of prostate cancer providers over time, patients were sorted into 3 fragmentation groups (low, intermediate, and high). The authors then examined annual per capita survivorship expenditures and a measure of quality (ie, repetitive prostate‐specific antigen [PSA] testing within 30 days) according to their fragmentation exposure using multinomial logistic regression.

RESULTS:

Patients with highly fragmented cancer care tended to be younger, white, and of higher socioeconomic status (all P < .001). Prostate cancer survivorship interventions were most common among patients with the highest fragmentation of care across providers (P < .001). After adjustment for clinical characteristics and prostate cancer survivorship interventions, higher degrees of fragmentation continued to be associated with repetitive PSA testing (13.6% for high vs 7.0% for low fragmentation; P < .001) and greater spending, particularly among patients not treated with androgen deprivation therapy.

CONCLUSIONS:

Fragmented prostate cancer survivorship care is expensive and associated with potentially unnecessary services. Efforts to improve care coordination via current policy initiatives, electronic medical records, and the implementation of cancer survivorship tools may help to decrease fragmentation of care and mitigate downstream consequences for prostate cancer survivors. Cancer 2011;. © 2011 American Cancer Society.     

In vivo biodistribution of dendrimers and dendrimer nanocomposites -- implications for cancer imaging and therapy

Our results indicate that the surface chemistry, composition, and 3-D structure of nanoparticles are critical in determining their in vivo biodistribution, and therefore the efficacy of nanodevice imaging and therapies. We demonstrate that gold/dendrimer nanocomposites in vivo, present biodistribution characteristics different from PAMAM dendrimers in a B16 mouse tumor model system. We review important chemical and biologic uses of these nanodevices and discuss the potential of nanocomposite devices to greatly improve cancer imaging and therapy, in particular radiation therapy. We also discuss major issues confronting the use of nanoparticles in the near future, with consideration of toxicity analysis and whether biodegradable devices are needed or even desirable.