Phase II study of temozolomide plus thalidomide for the treatment of metastatic melanoma.

Purpose: To further investigate the efficacy and safety of temozolomide plus thalidomide in patients with metastatic melanoma without brain metastases.

Patients And Methods: Patients with histologically confirmed advanced-stage metastatic melanoma were enrolled in an open-label, phase II study. The primary end point was response rate.

The case for polyvalent cancer vaccines that induce antibodies.

Antibodies are ideally suited for eradicating pathogens from the bloodstream and early tissue invasion. With regard to cancer cells, passively administered and vaccine induced antibodies have accomplished this, eliminating circulating tumor cells and systemic or intraperitoneal micrometastases in a variety of preclinical models. A series of cancer cell-surface differentiation antigens have now been identified and synthesized.

External breast prosthesis use: experiences and views of women with breast cancer, breast care nurses, and prosthesis fitters.

After mastectomy, the provision of an appropriate breast prosthesis can help to improve body image and quality of life and reduce associated emotional distress. Although up to 90% of women use an external breast prosthesis after mastectomy, little is known about their experiences and satisfaction with breast prosthesis use. Focus groups were conducted with women who had been fitted with an external breast prosthesis, breast care nurses, and prosthesis fitters to explore women's experiences of prosthesis use.

A preclinical study comparing approaches for augmenting the immunogenicity of a heptavalent KLH-conjugate vaccine against epithelial cancers.

Previously using a series of monovalent vaccines, we demonstrated that the optimal method for inducing an antibody response against cancer cell-surface antigens is covalent conjugation of the antigens to keyhole limpet hemocyanin (KLH) and the use of a saponin adjuvant. We have prepared a heptavalent-KLH conjugate vaccine containing the seven epithelial cancer antigens GM2, Globo H, Lewis(y), TF(c), Tn(c), STn(c), and glycosylated MUC1. In preparation for testing this vaccine in the clinic, we tested the impact on antibody induction of administering the individual conjugates plus adjuvant compared with a mixture of the seven conjugates plus adjuvant, and of several variables thought to augment immunogenicity.

The effectiveness of personalized smoking cessation strategies for callers to a Quitline service.

Aim: To assess the effectiveness of a program of computer-generated tailored advice for callers to a telephone helpline, and to assess whether it enhanced a series of callback telephone counselling sessions in aiding smoking cessation.

Design: Randomized controlled trial comparing: (1) untailored self-help materials; (2) computer-generated tailored advice only, and (3) computer-generated tailored advice plus callback telephone counselling. Assessment surveys were conducted at baseline, 3, 6 and 12 months.

Phase I trial of high dose paracetamol and carmustine in patients with metastatic melanoma.

Reduced glutathione (GSH) production by tumour cells has been proposed as a mechanism for resistance to alkylating agents. High levels of paracetamol can deplete intracellular GSH. We conducted a phase I trial of high dose paracetamol and carmustine (BCNU) in patients with advanced malignant melanoma to determine the optimal biological dose and the maximum tolerated dose (MTD) with the goal of increasing sensitivity to BCNU by GSH depletion.

On the power of chemical synthesis: immunological evaluation of models for multiantigenic carbohydrate-based cancer vaccines.

Synthetic carbohydrate cancer vaccines have been shown to stimulate antibody-based immune responses in both preclinical and clinical settings. The antibodies have been observed to react in vitro with the corresponding natural carbohydrate antigens expressed on the surface of tumor cells, and are able to mediate complement-dependent and/or antibody-dependent cell-mediated cytotoxicity. Furthermore, these vaccines have proven to be safe when administered to cancer patients.

Clinical results using biochemotherapy as a standard of care in advanced melanoma.

Phase II studies of biochemotherapy in metastatic melanoma patients have reported response rates of 47-63%. Even though these were highly selected patients, we were intrigued by these promising response rates and began using this regimen as standard care in advanced melanoma patients. We report the results of the first 65 patients with AJCC stage IV melanoma (n = 57) or unresectable stage III (n = 8) melanoma treated with concurrent biochemotherapy at Memorial Hospital.

Temozolomide plus thalidomide in patients with advanced melanoma: results of a dose-finding trial.

Purpose: To establish a safe and tolerated regimen of an oral cytotoxic agent, temozolomide, and a cytostatic agent, thalidomide, in patients with unresectable stage III or IV malignant melanoma.

Patients And Methods: Patients with unresectable stage III or IV melanoma without brain metastases were entered successively onto four treatment cohorts: level 1, temozolomide 50 mg/m(2)/d for 6 weeks followed by a 4-week break; levels 2, 3, and 4, temozolomide 75 mg/m(2)/d for 6 weeks followed, respectively, by breaks of 4, 3, and 2 weeks. Thalidomide was started at 200 mg/d, and escalated to a maximum dose of 400 mg/d.

Knowledge, attitudes and experience associated with testing for prostate cancer: a comparison between male doctors and men in the community.

Background: Debate about testing for prostate cancer using prostate-specific antigen (PSA) and digital rectal examination (DRE) continues. The evidence of benefit from screening for prostate cancer using PSA tests is inconclusive, and it is unclear how PSA can be used most effectively in the detection of prostate cancer. Given the lack of consensus, it is important that consumers understand the issues in a way that will permit them to decide whether or not to have a test and, if symptomatic, how their condition is managed.

T-cell responses against tyrosinase 368-376(370D) peptide in HLA*A0201+ melanoma patients: randomized trial comparing incomplete Freund's adjuvant, granulocyte macrophage colony-stimulating factor, and QS-21 as immunological adjuvants.

We conducted a randomized trial in HLA*A0201+ patientswith American Joint Committee on Cancer stage III or IV melanoma immunized with tyrosinase 368-376(370D) peptide and gp100 209-217(210M) peptide to compare the potency of three different adjuvants. Patients received 3 monthly immunizations with 500 microg of each peptide either with incomplete Freund's adjuvant (IFA), QS-21, or granulocyte macrophage colony-stimulating factor (GM-CSF). The primary end point was induction of IFN-gamma release by CD8+ T cells against tyrosinase and gp100 peptides measured by enzyme-linked immunospot assays without in vitro prestimulation measured pretreatment, 2 and 8 weeks after the third vaccination.

Vaccination with CD20 peptides induces a biologically active, specific immune response in mice.

CD20 is a 33-kD B-cell antigen that is expressed from the early pre-B-cell stage of development and is lost on differentiation of B cells into plasma cells. Because CD20 is expressed strictly by B cells, it is an attractive target for B-cell lymphoma therapy. Monoclonal antibodies to CD20 have been used successfully in the treatment of B-cell lymphomas.

Constructing an adenocarcinoma vaccine: immunization of mice with synthetic KH-1 nonasaccharide stimulates anti-KH-1 and anti-Le(y) antibodies.

There is mounting evidence to suggest that immunization-based strategies can be used to mobilize the human immune system against specific carbohydrate antigens displayed on the surface of cancer cells. Following isolation and identification, such antigens can be administered as conjugate vaccines. The tumor-associated carbohydrate antigen KH-1 is 1 such antigen and may serve as a potential target for immunization against adenocarcinoma.

Vaccines for melanoma: translating basic immunology into new therapies.

Advances in molecular biology and immunology in the past 10-15 years have allowed for a greater understanding of the molecules present on melanoma cells that are recognised by the immune system. The rising incidence of melanoma, combined with lack of efficacy of cytotoxic therapies, means there is a significant need for the development of effective immunotherapies. We discuss three types of vaccine for melanoma, which are currently in phase III clinical trials: allogeneic and autologous cellular vaccines, and carbohydrate vaccines.

Reevaluation of the cellular immune response in breast cancer patients vaccinated with MUC1.

Conjugation of antigens to a carrier protein like keyhole limpet hemocyanin (KLH) has proven effective in clinical trials for inducing antibodies against selected tumor antigens. The impact of this approach on T-cell immunity has not been previously tested. We utilized peripheral blood mononuclear cells (PBMC) obtained at leukapheresis from 6 breast cancer patients vaccinated 4 times each with a 106-amino acid-long MUC1 peptide conjugated with KLH plus immune adjuvant QS-21.

Comparison of antibody titers after immunization with monovalent or tetravalent KLH conjugate vaccines.

Antigens such as ganglioside GD3, neutral glycolipid Lewis(y) (Le(y)) and mucins MUC1 and MUC2 are over-expressed on the cell surface of many tumors. We have shown previously that conjugation of antigens such as these to keyhole limpet hemocyanin (KLH) and the use of immunological adjuvant QS-21 is the optimal approach for inducing high titer IgM and IgG antibodies. These antibodies are able to bind with natural antigens on the tumor cell surface and mediate complement dependent cytotoxicity and/or antibody dependent cell mediated cytotoxicity.

Keyhole limpet hemocyanin conjugate vaccines against cancer: the Memorial Sloan Kettering experience.

Passively administered and actively induced antibodies have been associated with the eradication of circulating tumor cells and micrometastases in mice and humans. We have identified a series of cell surface carbohydrate and peptide antigens on melanomas, sarcomas, and cancer of the breast, prostate. ovary, and lung tissues.

Knowledge, attitudes and self-care practices related to sun protection among secondary students in Australia.

The aim of this research was to ascertain changes in sun-related knowledge, attitudes and self-care practices among Australian secondary school students between 1993 and 1996. Two cross-sectional surveys of sun-related attitudes, beliefs and behavior of young people aged 12-17 years of age, were conducted in 1993 and 1996. Over 80% of adolescents at both time periods knew about the issues related to skin cancer prevention, frequency of burning and burning on cloudy days.

The effectiveness of callback counselling for smoking cessation: a randomized trial.

Aims: The development of acceptable, widely available and effective smoking cessation methods is central to public health strategy for tobacco control. We examined the effectiveness of a telephone callback counselling intervention, compared to the provision of self-help resources alone.

Methods: Participants were 998 smokers calling a state-wide "Quitline" service randomly allocated to either callback counselling or ordinary care.

Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients.

Human polymorphic epithelial mucin (PEM, MUC1) is a high molecular weight transmembrane glycoprotein expressed on the apical cell surface of glandular epithelium and is over-expressed and hypo-glycosylated in adenocarcinomas. The extracellular part of the molecule consists mainly of a variable number of 20 amino acid repeats that contain cryptic epitopes exposed in malignancy. The objective of our study was to determine whether humanized MUC1 MAbs and Abs induced by vaccination of breast cancer patients with MUC1 peptides can effect an antibody-dependent cell-mediated cytotoxicity (ADCC).

Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: a phase I trial.

The carbohydrate antigen globo H commonly found on breast cancer cells is a potential target for vaccine therapy. The objectives of this trial were to determine the toxicity and immunogenicity of three synthetic globo H-keyhole limpet hemocyanin conjugates plus the immunologic adjuvant QS-21. Twenty-seven metastatic breast cancer patients received five vaccinations each.

Vaccination with a bivalent G(M2) and G(D2) ganglioside conjugate vaccine: a trial comparing doses of G(D2)-keyhole limpet hemocyanin.

Immunization with GMK vaccine (G(M2) ganglioside conjugated to keyhole limpet hemocyanin mixed with QS-21 adjuvant) induces anti-G(M2) antibodies in close to 100% of patients. We found previously that anti-G(D2) antibodies could be induced in some patients using G(D2)-keyhole limpet hemocyanin + QS-21 (GDK). In this trial, we wished: (a) to determine whether immunization with both GMK and GDK vaccines could induce antibodies against both G(M2) and G(D2); and (b) to determine the optimal dose of GDK.

Recruitment methods for community-based screening for diabetic retinopathy.

Regular screening of all people with diabetes is the most efficient and cost-effective way to detect early stages of diabetic retinopathy so that laser treatment can be performed at the optimal time. A major aim of the Program for the Early Detection of Diabetic Retinopathy was to increase compliance with guidelines for screening for diabetic retinopathy. This community-based screening program used non-mydriatic retinal photography and was initiated in four areas of Victoria, Australia from 1996-1998.