Results of a phase II study using estramustine phosphate and vinblastine in combination with high-dose three-dimensional conformal radiotherapy for patients with locally advanced prostate cancer.

Purpose: To assess the feasibility and tolerance of neoadjuvant and concomitant estramustine phosphate and vinblastine (EV) with high-dose three-dimensional conformal radiotherapy (3D-CRT) for patients with unfavorable-risk prostate cancer.

Patients And Methods: Twenty-seven patients with unfavorable-risk prostate cancer were enrolled onto a prospective study to determine the feasibility of combining EV with 3D-CRT. Patients were eligible if any of the following requirements were satisfied: (1) Gleason score > or =8 and prostate-specific antigen (PSA) > 10 ng/mL; (2) Gleason score of 7 and PSA > 20 ng/mL; (3) clinical stage T3N0M0 disease with PSA > 20 ng/mL; (4) any patient with T4N0M0 disease; or (5) patients with TXN1MO disease.

The development of biologic end points in patients treated with differentiation agents: an experience of retinoids in prostate cancer.

The evaluation of new therapies in prostate cancer requires unique end points for agents with diverse mechanisms of action. Because retinoic acid may have a confounding effect on prostate-specific antigen, we incorporated a pathological end point into the outcome assessment of two sequential clinical trials using all-trans-retinoic acid (ATRA) and the combination of 13-cis-retinoic acid and IFN-2a (cRA¿IFN). Pre- and posttherapy tumor biopsy specimens were studied for histological changes, apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling assay), and proliferation index (Ki67).

Ifosfamide, paclitaxel, and cisplatin for patients with advanced transitional cell carcinoma of the urothelial tract: final report of a phase II trial evaluating two dosing schedules.

Background: A combination regimen of ifosfamide, paclitaxel, and cisplatin (ITP), recycled every 4 weeks, was reported in the treatment of previously untreated patients with advanced transitional cell carcinoma (TCC). This study sought to examine ITP at 3-week intervals to assess its feasibility and toxicity, compare the results for different schedules, and assess the impact of prognostic factors and postchemotherapy surgery on outcome.

Methods: ITP (ifosfamide 1.

Polyclonal antibodies from patients immunized with a globo H-keyhole limpet hemocyanin vaccine: isolation, quantification, and characterization of immune responses by using totally synthetic immobilized tumor antigens.

We have previously reported on a carbohydrate-based vaccine program for immunotherapy in cancer patients. One such vaccine, based on the globo H antigen conjugated to the protein keyhole limpet hemocyanin (KLH), has been in clinical evaluation. Although this and other carbohydrate vaccines have been shown to induce antibody responses, there are currently no quantitative data on the antibody levels achieved in immunized patients by these or other anti-cancer vaccines.

Outcome of postchemotherapy surgery after treatment with methotrexate, vinblastine, doxorubicin, and cisplatin in patients with unresectable or metastatic transitional cell carcinoma.

Purpose: The role of postchemotherapy surgery for patients with metastatic transitional cell carcinoma (TCC) is controversial. We retrospectively analyzed our experience with patients who underwent postchemotherapy surgery after methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy to assess an impact on long-term survival.

Patients And Methods: This report is based on the retrospective analysis of 203 patients with unresectable primary tumors or metastatic TCC, previously reported in five trials of M-VAC chemotherapy.

Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group.

Purpose: Prostate-specific antigen (PSA) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells. For patients with metastatic disease, changes in PSA will often antedate changes in bone scan. Furthermore, many but not all investigators have observed an association between a decline in PSA levels of 50% or greater and survival.

Prostate cancer cell cycle regulators: response to androgen withdrawal and development of androgen independence.

Background: Androgen withdrawal is a standard therapy for prostate cancer that results in a decrease in tumor volume and a decline in serum prostate-specific antigen in the majority of patients. To understand the factors associated with regression of prostate cancers after androgen withdrawal, we studied cell cycle regulator changes in the CWR22 human prostate cancer xenograft model.

Methods: Established tumors in nude athymic BALB/c mice were sampled at various times after androgen withdrawal and after the development of androgen independence.

Response of prostate cancer to anti-Her-2/neu antibody in androgen-dependent and -independent human xenograft models.

Antibody to the Her-2/neu gene product has been shown to inhibit the growth of breast cancer cells overexpressing Her-2/neu and to have clinical utility in treating breast cancer. We studied a recombinant, humanized anti-Her-2/neu antibody (Herceptin) in preclinical models of human prostate cancer. The androgen-dependent CWR22 and LNCaP human prostate cancer xenograft models and androgen-independent sublines of CWR22 were used.

Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy.

Purpose: The variation in reported survival of patients with metastatic transitional-cell carcinoma (TCC) treated with systemic chemotherapy may be a consequence of pretreatment patient characteristics. We hypothesized that a prognostic factor-based model of survival among patients treated with methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy could account for such differences and help guide clinical trial design and interpretation.

Patients And Methods: A database of 203 patients with unresectable or metastatic TCC was retrospectively subjected to a multivariate regression analysis to determine which patient characteristics had independent prognostic significance for survival.

Peptide and carbohydrate vaccines in relapsed prostate cancer: immunogenicity of synthetic vaccines in man--clinical trials at Memorial Sloan-Kettering Cancer Center.

Men with rising prostate-specific antigen (PSA) levels after primary therapies such as prostatectomy or radiotherapy represent a unique group for whom no standard treatment option exists. A variety of approaches including expectant monitoring, dietary modification, hormonal therapy, and alternative medicines have shown an impact on the rate of increase in PSA, but the overall effect on survival remains controversial. At Memorial Sloan-Kettering Cancer Center, we have focused our treatment approach on this cohort of patients in a series of phase I monovalent carbohydrate and glycoprotein-conjugate vaccine trials using the patients' immune system to generate an antitumor response.

Detection of prostatic specific membrane antigen messenger RNA using immunobead reverse transcriptase polymerase chain reaction.

The present study was performed to detect circulating prostatic carcinoma (PC) cells using a novel three-step immunobead reverse transcriptase (RT) polymerase chain reaction (PCR) assay for prostatic specific membrane antigen (PSMA) messenger RNA (mRNA). The sensitivity and specificity of this technique was assessed and the incidence of immunobead RT-PCR positivity correlated with progressive metastatic disease and serum prostatic specific antigen (PSA) levels. Fifty peripheral blood (PB) samples from 46 patients with PC were incubated with magnetic beads coated with Ber-EP4 antibody directed against the human epithelial antigen a membrane antigen widely expressed by epithelial cells.

Inactivation of the p53 pathway in prostate cancer: impact on tumor progression.

To determine the potential role of p53 inactivation in prostate cancer, we studied a well characterized cohort of 86 patients treated with radical prostatectomy. We analyzed patterns of p53, mdm2, and p21/WAF1 expression by immunohistochemistry. Results were then correlated with clinicopathological parameters of poor outcome, including time to PSA relapse.

Rising PSAs after primary therapy: active or passive intervention.

Prostate cancer that has relapsed biochemically after primary therapies, such as prostatectomy or radiation, remains a therapeutic challenge in that no standard treatment option exists for this patient. These patients are often young and may be offered androgen ablation as the mainstay of treatment. Many patients do not wish to undergo a regimen that may be associated with a variety of side effects that will impact on their quality of life.

Rhenium-186-labeled hydroxyethylidene diphosphonate dosimetry and dosing guidelines for the palliation of skeletal metastases from androgen-independent prostate cancer.

Rhenium-186 (tin)-labeled hydroxyethylidene diphosphonate (186Re-labeled HEDP) was evaluated in 27 men with progressive androgen-independent prostate cancer and bone metastases. Administered activities ranged from 1251 to 4336 MBq (33.8-117.

Overexpression of the cyclin-dependent kinase inhibitor p16 is associated with tumor recurrence in human prostate cancer.

The INK4A gene maps to the 9p21 region and was initially described [M. Serrano et al., Nature (Lond.

Carbohydrate vaccines in cancer: immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man.

The complex carbohydrate molecule globo H hexasaccharide has been synthesized, conjugated to keyhole limpet hemocyanin, and administered with the immunologic adjuvant QS-21 as a vaccine for patients with prostate cancer who have relapsed after primary therapies such as radiation or surgery. Globo H is one of several candidate antigens present on prostate cancer cells that can serve as targets for immune recognition and treatment strategies. The vaccine, given as five subcutaneous vaccinations over 26 weeks, has been shown to be safe and capable of inducing specific high-titer IgM antibodies against globo H.

Phase II trial of intermediate dose methotrexate in combination with vinblastine, doxorubicin, and cisplatin in patients with unresectable or metastatic transitional cell carcinoma.

Background: This study was undertaken to determine whether the use of intermediate dose methotrexate in combination with vinblastine, doxorubicin, and cisplatin as first-line therapy increases the proportion of major responders and overall survival in patients with unresectable or metastatic transitional cell carcinoma (TCC) of the urothelial tract.

Methods: Twenty-nine patients with histologically confirmed TCC received methotrexate at a dose of 1000 mg/m2 on Day 1 followed by leucovorin calcium rescue on Day 2 and vinblastine (3 mg/m2), doxorubicin (30 mg/m2), and cisplatin (70 mg/m2) (VAC) on Day 2. Therapy was recycled at 28-day intervals.

Prognostic significance of extent of disease in bone in patients with androgen-independent prostate cancer.

Purpose: To evaluate the prognostic significance of a bone scan index (BSI) based on the weighted proportion of tumor involvement in individual bones, in relation to other factors and to survival in patients with androgen-independent prostate cancer.

Patients And Methods: Baseline radionuclide bone scans were reviewed in 191 assessable patients with androgen-independent disease who were enrolled onto an open, randomized trial of liarozole versus prednisone. The extent of skeletal involvement was assessed by scoring each scan using the BSI and independently according to the number of metastatic lesions.

Can p53 help select patients with invasive bladder cancer for bladder preservation?

Purpose: We evaluated whether the p53 status of invasive bladder cancer may help to select patients for treatment strategies aimed at bladder preservation.

Materials And Methods: A total of 111 patients with muscle invasive (T2 to 3N0M0) transitional cell carcinoma of the bladder received neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy. Of these patients 60 (54%) had a complete clinical response (TO) to M-VAC.

Post-therapy serum prostate-specific antigen level and survival in patients with androgen-independent prostate cancer.

Background: With an hypothesis that post-chemotherapy changes in serum prostate-specific antigen (PSA) levels might serve as a surrogate marker for assessing prostate cancer outcome (i.e., survival), we studied the relationship between pretherapy and post-therapy prognostic factors and survival in patients with androgen-independent prostate cancer.

A Fully Synthetic Globo H Carbohydrate Vaccine Induces a Focused Humoral Response in Prostate Cancer Patients: A Proof of Principle.

Human trials on the globo H carbohydrate vaccine (see picture, KLH=the carrier protein keyhole limpet hemocyanin) show that it produces strong IgM, and in some cases IgG, responses in patients with progressive and recurrent prostate cancer. Furthermore, these antibodies not only recognize synthetic antigens, but also globo H-positive tumors in biopsy extracts and tumor tissues.

Urinary bombesin-like peptide levels in infants and children with bronchopulmonary dysplasia and cystic fibrosis.

Compared to normal infants and children, there are increased numbers of neuroendocrine cells with bombesin-like peptide (BLP) immunostaining in the lungs of infants and children with bronchopulmonary dysplasia (BPD) and cystic fibrosis (CF). However, there are no data documenting levels of urinary BLP in normal infants and children, or in children with lung disease. We therefore determined the normal developmental pattern for urinary BLP excretion in healthy infants and children, and in infants and children with BPD and CF, and correlated these findings with the subjects' clinical course.