Adjuvant Ovarian Suppression, High-dose Chemotherapy and Immunotherapy for Premenopausal Patients with High-risk Breast Cancer.

Background: Premenopausal patients with breast cancer and more than 10 positive axillary nodes (BC>10) have a poor prognosis: In these patients the best adjuvant therapy (CT) has not yet been established.

Patients And Methods: Forty-two BC>10 received, in sequence, the following adjuvant treatments: luteinizing hormone releasing hormone (LH-RH) analog for 5 years; anthracycline-based induction chemotherapy; radiation therapy; platinum-based high-dose CT, with autologous bone marrow transplantation; immunotherapy with interleukin 2 (IL2) and 13-cis retinoic acid (RA); anastrazole given 5 years to estrogen receptor-positive patients. Primary endpoints of the study were disease-free survival (DFS) and overall (OS) survival.

Primitive sarcoma of the breast: new insight on the proper surgical management.

Background: Primitive sarcoma of the breast is a rare and challenging disease at high risk of recurrence and with poor prognosis. There are controversies in the diagnosis and management of such solid tumor due to its rarity and heterogeneity. This sarcoma is poorly responsive to both chemotherapy and radiotherapy, thus, surgery is the first and most important therapeutic approach.

LH-RH analogues in the treatment of young women with early breast cancer: long-term follow-up of a phase II study.

To prevent premature ovarian failure (POF), high-risk, premenopausal women with early breast cancer were given a luteinizing-hormone releasing hormone (LH-RH) analogue during adjuvant chemotherapy. After an adriamycin-based regimen, patients received radiation therapy concomitant with cyclophosphamide, methotrexate and 5-fluorouracil. An aromatase inhibitor was given to patients positive for the estrogen receptor (ER+).

Anthracycline-based induction chemotherapy followed by concurrent cyclophosphamide, methotrexate and 5-fluorouracil and radiation therapy in surgically resected axillary node-positive breast cancer.

The present study aimed to determine the toxicity and efficacy of 4 courses of anthracyclines-taxane (AT) chemotherapy followed by radiation therapy (XRT) concurrent with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in surgically resected axillary node-positive (N+) breast cancer. A total of 200 women with N+ breast cancer were treated with adriamycin and docetaxel followed by XRT concurrent with six courses of CMF. Two courses of dose-dense chemotherapy with ifosfamide, carboplatin and etoposide, supported by pegfilgrastim, were administered to patients with >5 histologically confirmed axillary lymph node metastases and patients with triple-negative disease.

Vascular endothelial growth factor expression and T-regulatory cells in premenopausal breast cancer.

Estradiol (E2) plays a key role in human reproduction through the induction of vascular endothelial growth factor (VEGF) and T-regulatory cells (T-Regs), which are also important in breast cancer (BC) growth. The primary endpoint of the present study was the investigation of whether E2 suppression, chemotherapy and radiation therapy decreased the levels of VEGF and T-Regs of premenopausal patients with high-risk early BC. The secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS).

Triple-negative breast cancer: multipronged approach, single-arm pilot phase II study.

Anthracyclines (A) and taxanes (T) are standard first-line chemotherapy agents for patients with advanced breast cancer. Platinum analogues have also shown activity in the triple-negative breast cancer (TNBC) histology, but clinical data are limited. Here we report the long-term follow-up of a phase II study on TNBC treated with a combined modality therapy, including induction with AT, cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) with concurrent radiation therapy, and a dose-dense consolidation chemotherapy (HDCT) with carboplatin (CBDCA), ifosfamide (IFX), etoposide (VP-16).

Chemoembolization of unresectable hepatocellular carcinoma: Decreased toxicity with slow-release doxorubicin‑eluting beads compared with lipiodol.

Chemoembolization with lipiodol (TACE) improves survival of selected patients with unresectable hepatocellular carcinoma (HCC), but results in substantial toxicity. To improve treatment tolerance, we conducted this phase II study using doxorubicin-loaded beads (DC Beads®) delivered by selective transcatheter arterial chemoembolization (DEB-TACE). We compared the results with those obtained with TACE in our historical controls.

Premenopausal hormone-responsive breast cancer with extensive axillary nodes involvement: total estrogen blockade and chemotherapy.

Background: Poor prognosis is associated with estrogen- and/or progesterone receptor-positive (ER(+), PGR(+)) premenopausal breast cancer (PM-BC) with high Ki-67 labeling index and extensive axillary lymph node involvement. The role of adjuvant chemotherapy (CT) and hormonal therapy have not yet been established in these patients.

Patients And Methods: Twenty-five PM-BC patients received, in sequence, leuprorelin, taxane-anthracycline induction chemotherapy, radiation therapy, a platinum-based intensification high-dose CT, followed by leuprorelin and anastrazole for five years.

High-risk early breast cancer in patients under 40 years of age: Improved clinical outcome with total estrogen blockade and tailored chemotherapy.

This multicenter prospective trial assessed the outcome in 63 patients, 40 years of age or younger, with high-risk early breast cancer (HREBC), included in an ovarian protection study. The patients were treated with a luteinizing hormone-releasing hormone (LH-RH) analogue administered for 5 years, tailored chemotherapy and an aromatase inhibitor, in estrogen receptor-positive (ER(+)) patients. T-regulatory cells (T-regs) and vascular endothelial growth factor (VEGF) were measured at baseline and yearly.

Liposomal pegylated doxorubicin and oxaliplatin as salvage chemotherapy in patients with metastatic gastric cancer treated earlier.

The aim of this study was to evaluate the activity and safety of pegylated liposomal doxorubicin (PLD) and oxaliplatin (LOHP) as salvage chemotherapy in patients with metastatic gastric cancer (MGC) who had earlier been treated with docetaxel, capecitabine, 5-fluorouracil, and leucovorin. Treatment consisted of PLD (40 mg/m(2)) and LOHP (120 mg/m(2)) administered over 2 days, every 3 weeks. Response to therapy was assessed using the Response Evaluation Criteria In Solid Tumors; toxicity was evaluated by the National Cancer Institute common toxicity criteria (version 2.

Prolonged disease control after myeloablative chemotherapy, autologous transplantation and immunotherapy in high-risk early breast cancer.

Background: Failure to eradicate all cancer stem cells, lymphocytopenia, and high levels of vascular endothelial growth factor (VEGF) may explain the limited efficacy of high dose-chemotherapy (HDCT) with peripheral progenitor cell transplantation (PBPCT) in high-risk early breast cancer with more than 10 axillary nodes (HRBC).

Patients And Methods: With the aim of increasing patient's lymphocyte count and reducing VEGF, wich could translate into an improved immune function and a better clinical outcome, patients with HRBC, received HDCT, PBPCT and immunotherapy with interleukin-2 (IL-2) and 13-cis retinoic acid (RA).

Results: A total of 30 HRBC patients were entered into the study.

Maintenance immunotherapy in recurrent ovarian cancer: long term follow-up of a phase II study.

Objectives: Vascular endothelial growth factor (VEGF), a mediator of tumor-associated immunodeficiency, plays a key role in angiogenesis and is a prognostic factor in advanced ovarian cancer (AOC). Previously, we showed that low-dose interleukin-2 (IL-2) and 13-cis-retinoic acid (RA) improved the tumor-associated immunodeficiency and decreased VEGF in patients with AOC. Here, we report long term follow-up of a group of patients with platinum-sensitive AOC who were treated with IL-2 and RA.

Chemoradioimmunotherapy in locally advanced pancreatic and biliary tree adenocarcinoma: a multicenter phase II study.

Objectives: The antitumor activity and toxicity of a multi-step treatment were evaluated in patients with locally advanced, inoperable, or incompletely resected pancreatic (Pa) and biliary tree (Bt) adenocarcinomas (ADKs).

Methods: Fifty-four patients, 63% with Pa and 37% with Bt ADK, received 3 courses of cisplatin-gemcitabine induction chemotherapy. Progression-free (PF) patients were given consolidation radiotherapy with concurrent capecitabine.

Immunotherapy in patients with less than complete response to chemotherapy.

Background: Patients with metastatic solid tumors (MST) with less than a complete response to chemotherapy (L-CR), a depressed immune system and elevated serum vascular endothelial growth factor (VEGF) lack defined treatment options. The primary endpoint evaluated in this study was whether interleukin-2 (IL-2) and 13-cisretinoic acid (RA) treatment reduced VEGF and improved immune function in such patients. Secondary endpoints were objective response, relapse-free survival (RFS), and overall survival (OS).

Beta-interferon, retinoids and tamoxifen in metastatic breast cancer: long-term follow-up of a phase II study.

Based on a series of in vitro data, including the additive and/or synergistic antiproliferative effect of interferon and tamoxifen on breast cancer cell lines, and on clinical reports, we designed a pilot phase II study to test the activity and toxicity of simultaneous administration of beta-interferon (beta-IFN), retinoids (R) and tamoxifen (TAM) as a salvage therapy in a group of patients with metastatic breast cancer (MBC). Herein we describe the outcome of this cohort of patients after a median follow-up of 150 months. Sixty-five stage IV breast cancer patients, 13 pre-treated with hormones, 38 with chemotherapy and 15 with both, received, as a salvage therapy, TAM, beta-IFN and R.

Maintenance immunotherapy in metastatic breast cancer.

Maintenance chemotherapy provides only a modest survival advantage in metastatic breast cancer (MBC). We have previously shown that a maintenance immunotherapy (MI) regimen based on low-dose interleukin-2 (IL-2) and 13-cis retinoic acid (RA) improved the lymphocyte and natural killer cell (NK) counts, and CD4+/CD8+ ratio in patients with a clinical benefit from chemotherapy. With the aim of improving progression-free survival (PFS), 100 consecutive MBC patients with a clinical benefit from chemotherapy were treated with an MI.

Alternating XELFOX and XELFIRI in patients with metastatic colorectal cancer.

Background: To evaluate the antitumor activity and toxicity of 5-fluorouracil (FU)/leucovorin (LV) and capecitabine (C) given with either oxaliplatin (OX) or camptothecin (CPT-11) in the treatment of chemotherapy naive patients with metastatic colorectal cancer.

Materials And Methods: The outpatient treatment, consisted of 2 consecutive days of LV, 200 mg/m(2), 5-FU 400 mg/m(2), and C 2000 mg/m(2) that, in one cycle, was preceded by 2 days of OX 50 mg/m(2), and, in the subsequent cycle, by CPT-11, 90 mg/m(2).

Results: All 54 patients were assessable for toxicity and response.

Multicenter phase II study of chemoimmunotherapy in the treatment of metastatic melanoma.

Combining chemotherapy and immunotherapeutic agents such as interleukin-2 and interferon alpha-2b might improve treatment results in metastatic melanoma (MM) patients compared with chemotherapy alone. This prospective study evaluated the potential efficacy of a biochemotherapy regimen followed by maintenance biotherapy for the treatment of MM. Twenty-two patients with stage IV melanoma were treated for 5 consecutive days with cisplatin at 20 mg/m, vinblastine at 1.

A multicenter phase II study of pegylated liposomal doxorubicin and oxaliplatin in recurrent ovarian cancer.

Objective: Pegylated liposomal doxorubicin (PLD) and oxaliplatin (LOHP) are active as single agents in the treatment of recurrent ovarian cancer (ROC). This phase II study investigated the safety and activity of PLD and LOHP used in combination to treat ROC.

Methods: Eligibility criteria included disease recurrence after one (45%) or more lines (55%) of chemotherapy, performance status 3 months.

Multicenter phase II study of chemo-immunotherapy in the treatment of metastatic renal cell carcinoma.

The purpose of this study was to evaluate the potential efficacy of a chemo-immunotherapy regimen for the treatment of metastatic renal cell carcinoma (MRCC). Forty-one patients with progressing MRCC and with a median age of 63 years were recruited. Planned treatment consisted of 6 courses of capecitabine 1000 mg/m twice daily on days 1 to 14 every 4 weeks, pegylated alpha-interferon 2b 50 microg every week, interleukin-2 1.

Chemoimmunotherapy in the treatment of metastatic gastric cancer.

Docetaxel, capecitabine and 5-fluorouracil have been shown to be active in the treatment of metastatic gastric adenocarcinoma. Consistent with this finding, the aim of this study was to test this combination in a clinical trial. Forty-one patients with metastatic gastric adenocarcinoma and a median age of 64 years were recruited for the study.

Phase II study of interleukin-2 and 13-cis-retinoic acid as maintenance therapy in metastatic colorectal cancer.

Purpose: We have previously shown that low-dose interleukin-2 (IL-2) and 13-cis-retinoic acid (13-cis-RA) improved lymphocyte and natural killer (NK) cell count of patients with advanced tumors showing a clinical benefit from chemotherapy. The primary endpoint of this study was to ask whether IL-2 and 13-cis-RA improved (> or =30%) lymphocyte and NK cell count in patients with metastatic colorectal cancer (MCRC) that had a clinical benefit from induction chemotherapy. Secondary endpoint was the evaluation of toxicity, progression-free survival (PFS), and overall survival (OS).

Dose-finding study of docetaxel added to ifosfamide and cisplatin followed by concomitant capecitabine and radiotherapy in the treatment of locally advanced squamous cell carcinoma of the head and neck.

Background: Docetaxel (DOC) is a promising new drug in the management of squamous cell carcinoma of the head and neck. The aim of this phase I study was to determine the toxicity and maximum tolerated dose (MTD) as well as to obtain preliminary data on the activity of DOC combined with fixed doses of ifosfamide (IFO) and cisplatin (CDDP), followed by concomitant capecitabine (C) and radiation therapy in the organ-sparing treatment of patients with locally advanced, inoperable squamous cell carcinoma of the head and neck (A-SCCHN).

Patients And Methods: Chemotherapy and radiotherapy-naive patients with A-SCCHN were treated in cohorts of three with escalating doses of DOC administered on day 1.

Cardiac metastases in malignant fibrous histiocytoma. A case report.

Malignant fibrous histiocytoma metastasizing to the left ventricle is an uncommon form of cardiac malignancy. This report describes a rare case of left ventricular metastases from a malignant fibrous histiocytoma of the posterior compartment of the right thigh, recurring five years after treatment with surgery, hyperthermic perfusion of the limb and radiotherapy. As the patient presented symptoms of cardiac tamponade, open heart surgery was performed through a median sternotomy; however, the tumor was not resectable and only a biopsy was performed.