A randomized phase II study of combination, alternating and sequential regimens of doxorubicin and docetaxel as first-line chemotherapy for women with metastatic breast cancer.

Background: This randomized phase II study was conducted to evaluate the efficacy of doxorubicin and docetaxel (DOC) administered either as a combination, an alternating or a sequential regimen in women with metastatic breast cancer. Secondary objectives included overall response, time to progression, survival and safety.

Patients And Methods: Patients with breast cancer (n=123) were randomized to receive doxorubicin and DOC either in combination (60 mg/m2 of each drug), or by alternated or sequential schedule (100 mg/m2 DOC and 75 mg/m2 doxorubicin) every 3 weeks for a maximum of eight cycles as first chemotherapy for stage IV disease.

Molecular and functional bases of self-antigen recognition in long-term persistent melanocyte-specific CD8+ T cells in one vitiligo patient.

Vitiligo patients possess high frequencies of circulating CD8+ T lymphocytes specific for the melanocyte differentiation antigen Melan-A/MART-1. These self-specific T cells exhibit intact functional properties and their T cell receptors are selected for a narrow range of high affinities of antigen recognition, suggesting their important role in the pathogenesis of vitiligo. In order to understand the molecular base for this unexpected, optimal T cell receptor recognition of a self-antigen, a tetramer-guided ex vivo analysis of the T cell receptor repertoire specific for the Melan-A antigen in a patient affected by vitiligo is reported.

Evaluation of infectious complications and immune recovery following high-dose chemotherapy (HDC) and autologous peripheral blood progenitor cell transplantation (PBPC-T) in 148 breast cancer patients.

Background And Objectives: High-dose chemotherapy (HDC) with autologous PBPC-T has been reported to be effective in hematological and in selected solid malignancies. In this setting, infectious complications represent a relevant cause of morbidity.

Patients And Methods: To ascertain the incidence, types and factors influencing the development of early and late infections, we retrospectively analyzed 148 consecutive breast cancer (BC) patients receiving HDC and PBPC-T, both for primary high-risk BC (pBC) and metastatic disease (mBC).

Retrorectal tumours: a case report.

The authors describe a case of retrorectal tumour in a 48-year-old female. Retrorectal tumours are rare, and their diagnosis is notoriously difficult and late. In this case the first-step diagnosis was made on the basis of clinical findings and radiological investigations such as abdominal ultrasonography.

Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6.

We studied concentration, phenotype, and function of peripheral blood (PB) dendritic cells (DCs) from patients with multiple myeloma (MM). The absolute number of circulating precursors of myeloid and plasmacytoid DCs was significantly lower in MM patients than in healthy subjects. After maturation, PBDCs from MM patients showed significantly lower expression of HLA-DR, CD40, and CD80 antigens and impaired induction of allogeneic T-cell proliferation compared with controls.

Minimal tumor contamination of hematopoietic harvests from breast cancer patients can be easily detected by liquid culture assay.

Background: Recurrence after PBSC transplantation in breast cancer (BC) patients may be related to the reinfusion of tumor cells contaminating the graft. We have developed a liquid culture (LC) method for the identification of viable epithelial tumor cells in PBSC collections.

Methods: Mononuclear fraction from PBSC harvests of BC patients undergoing high dose chemotherapy (HDC) (adjuvant setting n = 60, metastatic disease n = 30) were seeded in petri dishes containing round cover slips.

Allogeneic blood stem cell transplantation after a reduced-intensity, preparative regimen: a pilot study in patients with refractory malignancies.

Background: The immune-mediated graft-versus-tumor (GVT) effect plays a therapeutic role in the treatment of patients with hematologic malignancies who undergo allogeneic hematopoietic stem cell transplantation (HSCT). More recently, it was reported that a GVT effect also occurred in patients who underwent transplantation for metastatic renal carcinoma. The authors carried out a pilot trial of allogeneic transplantation after a reduced-intensity, preparative regimen in patients with refractory malignancies, including solid tumors.

Diverse expansion potential and heterogeneous avidity in tumor-associated antigen-specific T lymphocytes from primary melanoma patients.

While tumor-associated antigen (TAA)-specific CD8(+) T lymphocytes have been detected in metastatic melanoma patients, immune response in early disease phases has not yet been carefully evaluated. We looked for circulating cytotoxic T lymphocytes (CTL) directed against Melan-A / MART1, tyrosinase, gp100 and MAGE-3 antigens in patients with a diagnosis of primary cutaneous melanoma by using fluorescent HLA-A2 tetramers. In five out of six cases high numbers of CD8(+)/tetramer(+) cells could be detected by flow cytometry, and in four patients lymphocyte populations specific for two different melanoma antigens (Melan-A/MART1 and tyrosinase) were contemporaneously present.

Pulmonary function and complications following chemotherapy and stem cell support in breast cancer.

Pulmonary complications are frequent in patients treated with high-dose chemotherapy and autologous bone marrow transplantation for breast cancer or other solid tumours. This study analyses the development of lung toxicity, changes in respiratory function and occurrence of clinical symptoms in a group of 24 patients (mean age 46+/-7 yrs) who underwent high-dose sequential chemotherapy (HDS) with autologous peripheral blood stem cell (PBSC) support for high risk breast cancer. Clinical examination, chest radiography and lung function tests were performed before the HDS and 1 and 3 months following transplantation.

Autologous platelet collection and storage to support thrombocytopenia in patients undergoing high-dose chemotherapy and circulating progenitor cell transplantation for high-risk breast cancer.

Objectives: The use of circulating progenitor cell support following high-dose chemotherapy for malignancies decreases but does not entirely abolish platelet transfusion requirement. We investigated the feasibility of supporting the posttransplant thrombocytopenic phase exclusively with autologous platelets collected by apheresis and cryopreserved.

Methods: 25 patients underwent plateletpheresis during the platelet rebound occurring after high-dose cyclophosphamide.

Megakaryocytic progenitors can be generated ex vivo and safely administered to autologous peripheral blood progenitor cell transplant recipients.

We evaluated different culture conditions to obtain a lineage-selected proliferation of clonogenic megakaryocytic progenitors (MP). In low-density (LD) or CD34+ cell cultures, the best results were obtained in serum-free medium in the presence of megakaryocyte growth and development factor, stem cell factor, interleukin-3 (IL-3), IL-6, IL-11, FLT-ligand, and macrophage inflammatory protein-1alpha. In paired studies, expansion of LD cells was less effective than expansion of CD34+ cells, and pre-enrichment of CD34+ cells using negative depletion of lineage-positive cells produced significantly larger quantities of MP than pre-enrichment using positive selection.

Medroxyprogesterone-acetate reverses the MDR phenotype of the CG5-doxorubicin resistant human breast cancer cell line.

In malignant cells multidrug resistance (MDR) is frequently associated with the expression of a 170 KDa P-glycoprotein (P-gp) in the plasma membrane. P-gp acts as an ATP-dependent efflux pump causing a decreased intracellular accumulation of structurally unrelated natural anticancer agents such as anthracyclines. Doxorubicin (DX) resistance is mostly related to the multidrug resistance gene product P-gp.

Effect of recombinant human erythropoietin on hematopoietic and non-hematopoietic malignant cell growth in vitro.

Background: Several clinical studies have shown that recombinant human erythropoietin (rHuEpo) can ameliorate the anemia associated with hematologic malignancies and solid tumors. On the other hand, only a few studies have been performed to investigate whether rHuEpo can affect or modulate the growth of malignant cells.

Materials And Methods: We studied the effects of rHuEpo (0.

Recombinant interferon-alpha 2b affects proliferation, steroid receptors and sensitivity to tamoxifen of cultured breast cancer cells (CG-5).

Exposure of CG-5 human breast cancer cells to recombinant interferon (IFN)-alpha 2b results in a significative inhibition of cell proliferation; this is observed when cells are cultured in their standard conditions and is not modified if serum concentration present in the culture medium is lowered. Estrogen receptors are increased in CG-5 cells following a 5 day treatment with concentrations of IFN-alpha 2b ranging from 10 to 1000 IU/ml of culture medium. Progesterone receptors seem to be more influenced by a longer treatment with the drug (7 days).

Antitumor effect of lonidamine alone or combined with tamoxifen or medroxyprogesterone acetate in breast cancer cells.

The effect of Lonidamine (LND) alone or combined with the antiestrogen Tamoxifen (TAM) or Medroxyprogesterone acetate (MPA) on cell proliferation and steroid hormone receptor content of a human estrogen sensitive breast cancer cell line was investigated. LND has a direct growth inhibitory action, even if used at relatively low concentrations (10(-7) M), and shows the maximum effect at 10(-4) M. The combination of LND with the antiestrogen does not produce a potentiation of the TAM-induced reduction of cell number, while the association of the drug with MPA seems more effective with respect to MPA alone, at least at certain concentrations.

Combination chemotherapy with cyclophosphamide, fluorouracil, and either epirubicin or mitoxantrone: a comparative randomized multicenter study in metastatic breast carcinoma.

From February 1987 to January 1989, 60 patients with advanced breast cancer and no prior chemotherapy for advanced disease were randomized and studied, with 31 treated with fluorouracil, epirubicin, and cyclophosphamide (FEC) and 29 patients with fluorouracil, mitoxantrone, and cyclophosphamide (FNC). Doses were 500 mg/m2 fluorouracil, 500 mg/m2 cyclophosphamide, and 50 mg/m2 epirubicin2 or 10 mg/m mitoxantrone, i.v.

Antiproliferative effect of lonidamine on a human glioblastoma multiforme cell line.

Recent data from phase II trials have shown that lonidamine (LND) is effective in the treatment of tumors of various histogenesis, including gliomas. In the present work, we tested the antiproliferative effect of LND on a human glioblastoma cell line (LI) in different culture conditions. When LI are cultured in their standard conditions, a reduction of cell growth is seen after 3 days of treatment with 10(-4) M LND.

Effects of natural beta-interferon and recombinant alpha-2B-interferon on proliferation, glucocorticoid receptor content, and antigen expression in cultured HL-60 cells.

In the current study, we investigated the effects of natural beta-interferon (beta-IFN) and recombinant alpha-2b-interferon (alpha-IFN) on the growth of the HL-60 cell line. Cells cultured in a medium that contains various concentrations (from 10 to 1000 IU/ml) of interferons showed a growth inhibition, which reaches the maximum after a 6-day treatment, at the highest dose used. Furthermore, we studied the effect of both beta-IFN and alpha-IFN on the level of glucocorticoid receptors.

Effect of methylprednisolone sodium succinate on quality of life in preterminal cancer patients: a placebo-controlled, multicenter study. The Methylprednisolone Preterminal Cancer Study Group.

The effectiveness of an 8-week, 125 mg/day intravenous course of methylprednisolone sodium succinate (MPSS) for improving quality of life in patients with preterminal cancer was investigated in a double-blind, placebo-controlled, multicenter study. Quality of life was assessed using the Nurses' Observational Scale for Inpatient Evaluation (NOSIE), the Linear Analog Self-Assessment Scale (LASA), and the Physicians' Global Evaluation. A total of 403 patients were enrolled: 207 were treated with MPSS and 196 were treated with placebo.

First-line combination chemotherapy with mitoxantrone and cyclophosphamide in advanced breast cancer.

In this study, 30 evaluable patients with advanced carcinoma of the breast were treated with cyclophosphamide 600 mg/m2 i.v. followed one day later with mitoxantrone (Novantrone; dihydroxyanthracenedione) 16 mg/m2 i.

[Controlled study of unspecific cellular immunity in cancer patients].

Cellular immunity has been studied in 92 patients with solid tumors undergoing surgery, in order to evaluate immunocompetence at the time of diagnosis and to assess the prognostic value of parameters of cellular immunity. The results show that total lymphocyte counts, T-lymphocyte counts and lymphocyte blastogenic responses are moderately depressed at diagnosis in the cancer patients as compared to age matched controls. These parameters of cell mediated immunity "in vitro" seem to be of limited prognostic value, since no correlation was found with the clinical course during the first 6 postoperative months.

High dose medroxyprogesterone acetate (MPA) treatment in metastatic carcinoma of the breast: a dose-response evaluation.

The results of controlled clinical trial that used high doses of medroxyprogesterone acetate (MPA) in the treatment of metastatic breast cancer are reported. Two treatment reigmens were used: regimen A, 500 mg daily with a total dose of 30 g; regimen B, 1,000 mg daily with a total dose of 60 g. The overall response rates were similar, with no statistically significant difference between the two treated groups.

Accumulation of 99m Tc-Sn-pyrophosphate in pleural effusions.

Accumulation of 99m Tc-Sn-pyrophosphate in pleural effusions has been evaluated in 56 patients grouped as follows: 8 with bacterial effusion (Group A), 27 with malignant effusion treated by local and/or parenteral antitumor chemotherapy (Group B), 21 with malignant effusion treated only by supportive therapy (Group C). Results, expressed as effusion to plasma PPi ratio, ranged from 0.1 to 0.