27 juli 2012: aanvullend op onderstaande informatie over pentostatin - nipent, een middel dat gebruikt wordt bij bepaalde vormen van immuuntherapie en stamceltransplantaties, hebben we het abstract van deze studie toegevoegd:  Pentostatin Plus Cyclophosphamide Safely and Effectively Prevents Immunotoxin Immunogenicity in Murine Hosts

Voor lopende en afgesloten studies met pentostatin ga naar deze pagina van clinical trials.gov

mei 2002:

Pentostatin - Nipent lijkt effectief bij verschillende bloedkankersoorten, waaronder chronisch lymfatische leukemie, hairy cell leukemie en ook een bepaalde niet-agressieve vorm van non-Hodgkin. 

De producent van Nipent, geeft in een zelfgeschreven persbericht een opsomming van een aantal studieresultaten. Er staat nergens bij waar deze studies zijn gepubliceerd en gehouden wat wel een minpunt is voor de geloofwaardigheid, maar toch wil ik u deze informatie niet onthouden. 

Een langjarige follow-up studie zou Nipent als solomiddel bij 180 hairy cell leukemie patiënten een respons hebben gegeven van 98 procent. Respons betekent niet genezen, maar wel goede reactie op de behandeling en resultaten lijken toch indrukwekkend. In een andere studie zijn 13 patiënten met een bepaalde niet-agressieve vorm van non-Hodgkin en chronische lymfatische leukemie behandeld met een mix van Nipent, cyclophosfamide en Rituximab. Tien van de 11 evalueerbare patiënten toonden duidelijke tumorremissie door deze aanpak.

Een fase II studie met 62 patiënten met chronische Lymfatische leukemie werden behandeld met een mix van Nipent en Rituximab. Van de 54 evalueerbare patiënten toonden 33 procent een duidelijk remissie. In een fase I studie werden 23 patiënten met verschillende hemaetologische kwaadaardige aandoeningen behandeld met Nipent voor het voorkomen van het graft-versus-host syndroom ( Afstotingsverschijnselen bij stam- en/of beenmergtransplantatie). van de 20 evalueerbare patiënten toonden 12 er een complete remissie, bij drie gedeeltelijke remissie, bij drie wisselende respons en bij drie toonde de ziekte progressie ondanks de behandeling. Van de 15 patiënten met 'myelodysplastic syndrome' toonden 13 een volledige remissie en geen afstotingsverschijnselen na een mix van Nipent met lokale bestraling en lichttherapie. Ik zal proberen of ik wat meer gedetailleerde informatie over deze studies kan krijgen. Onder deze studie staan een paar vragen over Nipent gehaald van de website van Supergen Inc. 


-- Supergen Says Study Shows Nipent Effective --

DUBLIN, Calif. -(Dow Jones)- SuperGen Inc. (SUPG) said several studies showed its anticancer drug, Nipent, can treat a variety of hematological malignancies. Nipent is currently marketed by SuperGen for the treatment of hairy cell leukemia, a potentially fatal cancer of the blood and bone marrow that is characterized by a reduction in white blood cells, red blood cells and platelets.
In a press release Friday, the biopharmaceutical company said a long-term follow-up study of 180 hairy cell leukemia patients treated with Nipent between 1986 and 2000 resulted in a response rate of 98%.

In another study, 13 patients with indolent, or non-aggressive, non-Hodgkin's lymphoma and chronic lymphocytic leukemia were given a three-pronged therapy consisting of Nipent, cyclophosphamide and Rituximab. Ten of the 11 patients who
could be evaluated showed the tumor response sought by the study. A Phase II multicenter clinical trial involving 62 patients with chronic lymphocytic leukemia was conducted to assess how effective and safe it was to use a combined treatment of Nipent and Rituximab. Of the 54 evaluable patients, 33% achieved an objective response.

In a Phase I study, 23 patients with a variety of hematological malignancies were enrolled to assess Nipent as a treatment for steroid refractory acute graft-versus-host disease. Twenty patients were evaluable for response and they included 11 complete responses, three partial responses, three with mixed responses and three with progressive disease. Fifteen patients with myelodysplastic syndrome received a new preparative regimen consisting of Nipent, low-dose radiation and photophoresis treatments - where blood is exposed to ultraviolet light - prior to an allogeneic bone marrow transplant. Thirteen patients experienced full engraftment and subsequently, full remission.

Pentostatin Plus Cyclophosphamide Safely and Effectively Prevents Immunotoxin Immunogenicity in Murine Hosts

Clin Cancer Res. Author manuscript; available in PMC 2012 June 1.
Published in final edited form as:
PMCID: PMC3107891
NIHMSID: NIHMS290602

Pentostatin Plus Cyclophosphamide Safely and Effectively Prevents Immunotoxin Immunogenicity in Murine Hosts

Abstract

Purpose

The success of immunotoxin therapy of cancer is limited by host production of neutralizing antibodies, which are directed toward the Pseudomonas exotoxin A (PE) component. In this proof-of-principle study using a well-established murine model, we hypothesized that a newly developed immune depletion regimen consisting of pentostatin plus cyclophosphamide would abrogate anti-immunotoxin reactivity.

Experimental Design

BALB/c hosts were injected weekly with recombinant immunotoxin (RIT) SS1P, which is an anti-mesothelin Fv antibody fragment genetically fused to a 38 kDa portion of PE, and has been evaluated in clinical trials. Experimental cohorts received induction chemotherapy consisting of pentostatin (P) plus cyclophosphamide (C) prior to initial RIT exposure; some cohorts received further maintenance PC therapy of varying intensity just prior to each weekly RIT challenge. Cohorts were monitored for T, B, and myeloid cell depletion and for total anti-SS1P antibody (Ab) formation.

Results

Controls uniformly developed anti-SS1P Ab after the third RIT exposure. Induction PC therapy reduced the frequency of hosts with anti-SS1P Ab. Abrogation of antibody generation was improved by maintenance PC therapy: nearly 100% of recipients of intensive PC maintenance were free of anti-SS1P Ab after 9 weekly RIT doses. The most effective PC regimen yielded the greatest degree of host B cell depletion, moderate T cell depletion, and minimal myeloid cell depletion.

Conclusions

Induction and maintenance PC chemotherapy safely prevented anti-immunotoxin antibody formation with uniform efficacy. These data suggest that immunotoxin therapy might be used in combination with pentostatin plus cyclophosphamide chemotherapy to improve the targeted therapy of cancer.

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