Side effects of interferon-alpha therapy.

Aim: Interferon-alpha (IFN-alpha) has been extensively explored for its efficacy in various disease conditions and is currently used as a standard treatment in several of these. Its use is accompanied by a wide variety of possible side effects. These side-effects may hamper reaching and maintaining the dose needed for maximal therapeutic effect while their occurrence can outweigh clinical benefit of IFN-alpha treatment.

Role of allogeneic stem cell transplantation in current treatment of acute myeloid leukemia.

Allogeneic hematopoietic stem cell transplantation (alloSCT) has been established as an effective consolidation therapy in acute myeloid leukemia (AML) in first or subsequent remission. Although it effectively prevents relapse, treatment-related mortality (TRM) associated with alloSCT may compromise that beneficial effect. As a result, alloSCT may be restricted to patients with a relatively high risk of relapse.

Phase I and pharmacokinetic study of the dolastatin 10 analogue TZT-1027, given on days 1 and 8 of a 3-week cycle in patients with advanced solid tumors.

Purpose: TZT-1027 [N(2)-(N,N-dimethyl-l-valyl)-N-[(1S,2R)-2-methoxy-4-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[(2-phenylethyl)]amino]propyl]-1-pyrrolidinyl]-1-[(S)-1-methylpropyl]-4-oxobutyl]-N-methyl-l-valinamide] is a cytotoxic dolastatin 10 derivative inhibiting microtubule assembly through the binding to tubulins. The objectives of this phase I study was to assess the dose-limiting toxicities (DLT), to determine the maximum tolerated dose, and to study the pharmacokinetics of TZT-1027 when given i.v.

Gene therapy in in vivo isolated perfusion models.

Locoregional administration of a genetic construct by means of in vivo, in situ isolated perfusion (IP) of a target organ or extremity is a method that may increase in vivo efficacy. Vascular isolation and perfusion minimizes systemic exposure and thereby reduces unwanted side effects. Isolated hepatic perfusion (IHP) is the most extensively studied IP model, especially in gene therapy protocols for inborn errors of metabolism.

Successful treatment of low-grade oligodendroglial tumors with a chemotherapy regimen of procarbazine, lomustine, and vincristine.

Background: Anaplastic oligodendroglioma (OD) tumors, especially those with the combined loss of the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q), are sensitive to chemotherapy. Only limited data are available on the role of chemotherapy in low-grade OD. The authors retrospectively studied the outcome of the procarbazine, lomustine, and vincristine (PCV) chemotherapy regimen in a group of 16 patients with newly diagnosed OD and 5 patients with recurrent low-grade OD.

Isolated hypoxic hepatic perfusion with orthograde or retrograde flow in patients with irresectable liver metastases using percutaneous balloon catheter techniques: a phase I and II study.

Background: Isolated hepatic perfusion for irresectable metastases confined to the liver has reported response rates of 50% to 75%. Magnitude, costs, and nonrepeatability of the procedure are its major drawbacks. We developed a less invasive, less costly, and potentially repeatable balloon catheter-mediated isolated hypoxic hepatic perfusion (IHHP) technique.

Real-time pharmacokinetics guiding clinical decisions; phase I study of a weekly schedule of liposome encapsulated paclitaxel in patients with solid tumours.

The purpose of this weekly schedule phase I study of liposome encapsulated paclitaxel (LEP) was to define the maximum-tolerated dose (MTD), the recommended dose (RD), the dose-limiting toxicities (DLTs), the pharmacokinetic profiles, and to evaluate preliminarily antitumour effects in patients with refractory solid malignancies. LEP was administered as an intravenous (i.v.

Liquid chromatographic assays for DE-310, a novel camptothecin analog, and two major enzymatic products in human matrices.

Assays were developed for determination of DE-310, a carboxymethyldextran polyalcohol conjugate of the topoisomerase I inhibitor DX-8951 (exatecan) and two enzymatic products (i.e. glycyl-DX-8951 and unconjugated DX-8951) in human whole blood, erythrocytes and saliva.

12p-amplicon structure analysis in testicular germ cell tumors of adolescents and adults by array CGH.

All invasive testicular germ cell tumors of adolescents and adults (TGCTs), that is, seminomas and nonseminomas, show gain of 12p sequences, mostly as isochromosomes. Although several candidate genes have been suggested, the relevant gene(s) have not been identified yet. About 10% of testicular seminomas, however, show a more restricted amplification of the 12p11.

Isolated limb perfusion in the management of locally advanced extremity soft tissue sarcoma.

In conclusion, ILP is an interesting and important treatment option in the management of locally advanced extremity soft tissue sarcomas. Large medical centers, dealing with referrals and an important caseload of STS patients, should develop this treatment option and have it readily available to offer patients the best chances for limb salvage. In Europe, the success of TNF-based ILP has lead to the training, accreditation, and activation of TNF-based ILP programs in over 30 cancer centers since the approval of TNF for this indication in 1999.

Neuropsychiatric side effects of interferon-alfa therapy.

Aim: Immunotherapy with interferon-alfa (IFN-alfa) is used in a variety of diseases in- and outside clinical trials (e.g., chronic hepatitis, melanoma, chronic myelogenous leukemia, renal cell carcinoma, multiple myeloma).

European approach to adjuvant treatment of intermediate- and high-risk malignant melanoma.

Adjuvant therapies for patients with melanoma at high risk of relapse whether local, such as excision margins, elective regional lymph node dissection (ELND), and prophylactic isolated limb perfusion (ILP), or systemic, such as chemotherapy, immunotherapy, immunochemotherapy, or vaccination therapy, have little or no impact on survival when evaluated in randomized trials. The European approach to the treatment of each stage of malignant melanoma is characterized by thoughtful caution with particular attention being paid to the avoidance of unwarranted mutilation or toxicity because phase 3 studies have failed to demonstrate unequivocal benefits for a more aggressive approach. In Europe, there is no standard adjuvant systemic therapy; high-dose interferon (IFN) is used sporadically in individual patients by some physicians, but there is little enthusiasm for adopting this regimen as the standard of care because of its high toxicity profile and the lack of a clear beneficial impact on long-term survival.

The role interferon-alpha in malignant melanoma remains to be defined.

Interferon-alpha (IFNalpha) is a pleiotropic cytokine with various direct and indirect inflammatory response modulating activities. Some of these activities may have direct or indirect antitumour effects. For such a wide range of biological activities, the dose for optimal biological activity may differ greatly from the maximally tolerated dose as different effects are mediated by different concentrations of IFNalpha.