22 februari 2012: Bron: Expert Opin Pharmacother. 2010 Aug;11(11):1915-23.

Pixantrone heeft in de afgelopen jaren in verschillende studies bewezen een uitstekend middel te zijn voor bepaalde vormen van gevorderde en agressieve lymfklierkanker - non-Hodgkin. Zo bleek in een Fase III studie dat patiënten die pixantrone kregen een betere respons hadden (20% vs 6%) en een mediaan langere ziektevrije tijd (10.3 vs 7.6 months) in vergelijking met andere vormen van chemo. Het heeft wel even geduurd want al in 2003 waren er berichten over de eerste goede resultaten met pixantrone en nu meldt Medscape dat de Europese commissie overweegt om pixantrone officeel goed te keuren als medicijn bij lymfklierkanker - non-Hodgkin. Achtereenvolgens een abstract van een review studie, daaronder de berichtgeving uit 2003. Het volledige studierapport van de review studie kunt u tegen betaling inzien als u hier klikt.

Pixantrone for the treatment of aggressive non-Hodgkin lymphoma.

d.d. 25 augustus 2003:

Pixantrone lijkt uitstekend middel tegen uitgezaaide non-Hodgkin, waar eerder chemo bij faalde, zo blijkt uit een fase II studie.
30% van de deelnemende patiënten reageerde goed op de therapie met Pixantrone waarvan 17 % binnen twee jaar een volledige verdwijning van de ziekte mocht beleven. Deze studie is gepubliceerd in het augustusnummer van Haematologica, Journal of Haematology (Borchmann et al., Volume 88, No. 8).
Bijzonder aan deze resultaten is toch ook wel dat het merendeel van de deelnemende patiënten al chemo en andere behandelingen hadden gevolgd maar zonder resultaat.
Dan is een 17% complete remissie wel heel bijzonder. We moeten er wel bij aantekenen dat dit persbericht door het bedrijf dat pixantrone produceert naar buiten is gebracht
 en de studie niet langer is gevolgd dan twee jaar, maar dan nog is het een bijzonder resultaat afgezet tegen statistische gegevens van de resultaten van een behandeling van non-Hodgkin. .

Phase II Results Demonstrate Long Lasting Tumour Responses for
Pixantrone in Relapsed Aggressive NHL

BRESSO, Italy, Aug. 26 /PRNewswire-FirstCall/ -- Novuspharma SpA (Nuovo
Mercato: NOV.MI), a biopharmaceutical company focused on developing novel
treatments for cancer, today announces the publication of the results of a phase
II study for Pixantrone (BBR 2778) in relapsed aggressive non-Hodgkin's lymphoma
(NHL). These results demonstrated an overall response rate of 30%, with 17% of
patients experiencing a complete disappearance of their tumour following
Pixantrone therapy. Response to treatment was long lasting, averaging 11
months, with some patients still in remission 24 months following treatment.
Grade 4 neutropenia was the most frequently reported side effect, observed in 13
patients and requiring dose reduction in only 5 patients. The results were
published in the August issue of Haematologica, Journal of Haematology
(Borchmann et al., Volume 88, No. 8), in a paper entitled: Phase-II study of the
new aza-anthracenedione BBR 2778 in patients with relapsed aggressive
non-Hodgkin's lymphomas.
"We are extremely encouraged by the high rate of durable tumour responses
revealed by these results, especially when one considers that the majority of
these patients were elderly, had chemotherapy-resistant disease and almost all
had failed prior anthracycline-containing regimens," noted Silvano Spinelli,
Chief Executive Officer of Novuspharma.
"This impressive efficacy, coupled with the low incidence of cardiac-related
events despite re-exposure to therapeutic doses of Pixantrone, supports the
preclinical profile which suggested that Pixantrone may be less cardiotoxic and
more effective than existing anthracyclines and anthracenediones. Taken
together with our phase I experience in a similar population of patients with
aggressive NHL, this study increases our experience with single-agent Pixantrone
to 42 patients where we have observed 7 complete remissions and 5 partial
remissions. We believe this data will serve as the basis for planning a pivotal
trial in the third line treatment setting for aggressive NHL, which we would aim
to initiate early next year."

Trial design and patient characteristics
This study was an open-label, non-randomised, non-comparative, multicentre
phase II trial, which enrolled patients with relapsed aggressive NHL, as defined
by the REAL classification. Single agent Pixantrone was administered at 85
mg/m(2) on day 1, 8 and 15 of a 4-week cycle. Pixantrone belongs to the DNA
intercalator family of chemotherapy agents, which include the widely used
anthracyclines and anthracenediones. These agents are associated with a high
rate of tumour responses in blood borne tumours such as lymphoma and are
potentially curative in front-line therapy. However, the currently marketed
agents from this class suffer from cumulative cardiotoxicity, which prevents
them being used in those patients who relapse. Pixantrone was designed by
scientists at Novuspharma by modifying the structure of the currently marketed
DNA intercalators to remove those portions of the molecules responsible for
cardiotoxicity, while retaining those responsible for anti-tumour activity.
Of the 33 patients enrolled in the trial, 78% had chemotherapy-resistant
disease, having received 2 or more prior chemotherapy regimens, with their
cancer progressing within 123 days following their last treatment on average.
Patients had previously received 300mg/m2 of anthracycline on average (range
100-600mg/m2) which would typically make them ineligible for further treatment
with currently marketed anthracycline agents. Pixantrone was considered as
therapy for these relapsed patients due to the potentially superior cardiac
safety profile it displayed in preclinical studies compared to doxorubicin and
mitoxantrone. Of the 33 patients enrolled, 22 (67%) were over the age of 65,
25 had advanced stage disease (stage III or IV) and 15 had extra-nodal disease
(i.e. their cancer had spread from the lymphatic system). Of the 33 patients
enrolled, 7 had mantle cell lymphoma, which represents a particularly resistant
and hard to treat form of lymphoma.

Efficacy and safety results
The primary objective of the trial was to evaluate the efficacy of Pixantrone
in terms of the overall patient response rate (CR+PR) according to the WHO
criteria. 30 patients were evaluable for a response, of which 5 achieved a
complete response (CR) and 4 achieved a partial response (PR), representing an
overall response rate of 30% (27% on an intent to treat basis). 5 additional
patients achieved an unconfirmed partial response (PRu, i.e. a response
determined by a single measurement but not confirmed 12 weeks later) and 3
patients achieved stable disease. Tumour responses were durable, lasting over
24 months (range 2.3 to 24+ months). Notably, of the 7 patients with mantle
cell lymphoma, 6 experienced a response, with 1 patient achieving a CR and 5
patients having a PRu.
Additional objectives of the trial included an assessment of progression-free
survival, overall survival and safety. Among the patients who responded to
therapy, the average time to tumor progression was 11 months from the time of
first response (2.3 to 24+ months). Follow-up is still ongoing. 19 patients
had died of disease progression 12 months after study termination. The most
frequently reported toxicity associated with Pixantrone treatment was
neutropenia (depressed levels of white blood cells), with grade 4 neutropenia
being seen in 13 of 33 patients (39%). Generally this was short lived, lasting
a median of 7.5 days and could be easily controlled using immune cell growth
factors. Five patients required dose reduction for neutropenia. One patient
experienced grade 4 anemia, with no patients experiencing grade 4
thrombocytopenia (reduction in clot forming platelets).
Pixantrone's cardiac safety was assessed by using a MUGA-scan to monitor the
left ventricular ejection fraction (LVEF) of the heart. An absolute decrease in
LVEF greater than 10% and possibly treatment related was seen in 3 patients and
this was accompanied by cardiac symptoms in 2 patients. All 3 of these patients
had previously received the currently marketed DNA intercalators and 1 had a
pre-existing cardiac condition. Such a low level of cardiac events is
encouraging considering that the majority of patients had previously received
their lifetime maximum permitted dose of DNA intercalators/anthracyclines and
normally would have been precluded from receiving further treatment with these
agents.

lymfklierkanker, pixantrone

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• Pixantrone: FDA heeft grote vraagtekens bij gepresenteerde fase III studieresultaten met Pixantrone bij lymfklierkankerpatienten - non-Hodgkin waar eerder chemo faalde.

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• Reguliere oncologie: Lymfklierkanker: een overzicht van belangrijke studies en recente ontwikkelingen in de reguliere zorg