17 december 2013: Lees ook het artikel over goede resultaten van dasatinib en nilotinib bij CML en ALL in vergelijking met Gleevec. 

15 augustus 2011: ik ben kanker-actueel aan het herzien. Met Gleevec, zie onderstaand artikel,  is heel veel meer onderzoek gedaan afgelopen jaren en de opvolgers, Nipent en Sugent  worden ook al weer enkele jaren in de praktijk toegepast. Echter een genezende behandeling voor met name CML is nog steeds niet gevonden. Toch is er wel hoop. Medscape schreef een mooi samenvattend artikel over de huidige stand van zaken bij vormen van leukemie.  Als u hier klikt  kunt u dit artikel vrij inzien. Zo begint dit artikel:

There are a significant number of patients diagnosed with acute leukemia who either fail to achieve remission or who relapse thereafter. Challenges in treating this patient population include accurately assessing prognosis of disease and whether remission can be achieved; assessing the ability of patients to tolerate aggressive salvage therapies; choosing a salvage therapy that is most likely to succeed; and identifying suitable patients for hematopoietic stem cell transplantation. Despite the development of a variety of new investigational therapies, relapsed or refractory acute myeloid leukemia remains a difficult clinical problem. Clinicians will need to consider all currently available approaches, including cytotoxic chemotherapy, targeted agents, and allogeneic stem cell transplantation, to optimize outcomes. Read more>>>>>>

Zoals Novartis de producent van Gleevec al eerder meldde, zie ook op deze pagina,  zijn nu de resultaten met Gleevec opnieuw bevestigd in een grote trial met CML patiënten. Het volgende artikel is afgeleid van de studiepublicatie in de New England Journal of Medicine en geeft aan dat het middel Imatinib Mesylate (een andere naam voor Gleevec) bijzonder hoge respons gaf bij 454 patiënten in het M.D. Anderson Kankercentrum in Houston waar de normale standaard behandeling met bv. interferon alfa niet aansloeg. In dit artikel wordt gesproken over 60% (cytogenetisch) tot 95% haematologische) respons, met een follow-up resultaat van bijna 90% waarbij de patiënten geen progressie of recidief toonden. Significante bijverschijnselen waren zeldzaam en de haematologische klachten waren goed te behandelen aldus de onderzoekers in dit artikel. Opvallend is dat op de website van het M.D. Anderson Kankercentrum zelfs deze behandeling met Imatinib Mesylate (Gleevec)  nu wordt verkozen boven een beenmerg- of stamceltransplantatie. Ik moet zeggen dat dit toch wel erg bijzonder is. Voor meer informatie over trials met Imatinib Mesylate (Gleevec) zie deze websitepagina van het M.D. Anderson Kankercentrum.

 

Hier eerst het abstract van het gepubliceerde onderzoek gevolgd door een kort citaat over waarom het M.D. Anderson Kannkercentrum deze aanpak met Imatinib Mesylate verkiest boven een beenmerg- of stamceltransplantatie.

Volume 346:645-652 February 28, 2002 Number 9 

Hematologic and Cytogenetic Responses to Imatinib Mesylate in Chronic Myelogenous Leukemia

Hagop Kantarjian, M.D., Charles Sawyers, M.D., Andreas Hochhaus, M.D., Francois Guilhot, M.D., Charles Schiffer, M.D., Carlo Gambacorti-Passerini, M.D., Dietger Niederwieser, M.D., Debra Resta, R.N., Renaud Capdeville, M.D., Ulrike Zoellner, M.Sc., Moshe Talpaz, M.D., Brian Druker, M.D., for the International STI571 CML Study Group 

Background Chronic myelogenous leukemia (CML) is caused by the BCR-ABL tyrosine kinase, the product of the Philadelphia chromosome. Imatinib mesylate, formerly STI571, is a selective inhibitor of this kinase. 

Methods A total of 532 patients with late–chronic-phase CML in whom previous therapy with interferon alfa had failed were treated with 400 mg of oral imatinib daily. Patients were evaluated for cytogenetic and hematologic responses. Time to progression, survival, and toxic effects were also evaluated. 

Results Imatinib induced major cytogenetic responses in 60 percent of the 454 patients with confirmed chronic-phase CML and complete hematologic responses in 95 percent. After a median follow-up of 18 months, CML had not progressed to the accelerated or blast phases in an estimated 89 percent of patients, and 95 percent of the patients were alive. Grade 3 or 4 nonhematologic toxic effects were infrequent, and hematologic toxic effects were manageable. Only 2 percent of patients discontinued treatment because of drug-related adverse events, and no treatment-related deaths occurred. 

Conclusions Imatinib induced high rates of cytogenetic and hematologic responses in patients with chronic-phase CML in whom previous interferon therapy had failed. 

Source Information

From the M.D. Anderson Cancer Center, Houston (H.K., M.T.); the University of California at Los Angeles, Los Angeles (C Sawyers); Universitätsklinikum Mannheim der Universität Heidelberg, Mannheim, Germany (A.H.); Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Wayne State University, Detroit (C Schiffer); San Gerardo Hospital and National Cancer Institute, Milan, Italy (C.G.-P.); University of Leipzig, Leipzig, Germany (D.N.); Novartis Pharmaceuticals, East Hanover, N.J., and Basel, Switzerland (D.R., R.C., U.Z.); and Oregon Health Sciences University, Portland (B.D.). 

Address reprint requests to Dr. Kantarjian at the Department of Leukemia, Box 428, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, or at hkantarj@mdanderson.org.

Current Research Directions in CML

Prior to the advent of imatinib mesylate, our treatment decisions in CML were based on the one-year estimated mortality with allogeneic SCT. If it was 20% or less (younger patients, related donor) allogeneic SCT was recommended; if it was over 20%, allogeneic SCT was delayed until the patient failed to respond cytogenetically after one year of interferon alpha based therapy.

Since the discovery of imatinib mesylate, our treatment algorithm in CML has changed. With such effective therapy (discussed earlier), even a low transplant mortality of 5% to 10% (not considering the morbidities) may be too high a risk for initial therapy with the potential of cure. If imatinib mesylate could prolong the median survival to 10 years or more (thus changing the course of CML to that similar to polycythemia vera or essential thrombocytosis), or if it could lead to an increased 10 year event-free survival (from the 10% to 15% observed with interferon-based therapy) to 30% to 50%, then it is evident that the best role of allogeneic SCT would be in patients who become resistant to imatinib mesylate. Our current advice to patients with newly diagnosed CML is to be treated initially with imatinib mesylate, and to consider allogeneic SCT only if their disease fails to respond to imatinib mesylate ± interferon alpha therapy. This recommendation is based on:

  1. The superior results of imatinib mesylate compared with interferon alpha (hence the expectation of much better long-term results)
  2. The continued positive and improved cytogenetic responses with imatinib mesylate with longer-term follow-ups
  3. The absence of any significant or unexpected toxicities

Our recommendation will continue to be so, unless we start observing worsening of the responses, or new unexpected long-term toxicities. While prognosis in CML has improved drastically, the long-term aims of our research are to produce the highest possible rates of complete cytogenetic and molecular remissions, and consequently the highest possible rates of long-term event-free survival (and hopefully cures) with the lowest possible toxicity, either without needing allogeneic SCT, or through sequencing allogeneic SCT in patients whose CML stops responding to imatinib mesylate based regimens. In the next section, we will describe some of our research directions in CML.

Hier het persbericht van Rueters Health zoals dat is afgeleid van de studie gepubliceerd in the New England Journal of Medicin d.d. 27 febr. 2002.

-High Response Rates to Imatinib Seen in CML Patients

NEW YORK (Reuters Health) Feb 27 - Treatment with imatinib mesylate induces cytogenetic and hematologic responses in a high proportion of patients with chronic myelogenous leukemia (CML) who have failed interferon therapy, according to a report published in the February 28th issue of The New England Journal of Medicine. 
Imatinib (Gleevec, Glivec; Novartis), a BCL-ABL tyrosine kinase inhibitor, was approved by the US Food and Drug Administration in May 2001 for the treatment of CML. Earlier this month, the FDA extended the drug's indications to the treatment of gastrointestinal stromal tumors (see Reuters Health report, February 4, 2002). 

Dr. Hagop Kantarjian, from the M. D. Anderson Cancer Center in Houston, and colleagues assessed the outcomes of 454 patients with chronic-phase CML who were treated with 400 mg/day of imatinib. All of the patients had previously failed treatment with interferon alfa. The median followup period was 18 months. 

Imatinib induced a major cytogenetic response in 60% of patients and a complete hematologic response in 95%, the researchers note. At followup, nearly 90% of patients had no evidence of CML progression to accelerated or blast phases and 95% of patients were alive. 

Significant nonhematologic adverse effects were uncommon and the toxic hematologic effects that occurred were manageable, the authors note. The adverse effect-related treatment discontinuation rate was 2.1%. 

"Regimens that combine imatinib with other agents may improve results further, and ongoing clinical trials are testing the feasibility of these approaches," the researchers state. "The activity of imatinib is also being investigated in patients with newly diagnosed CML...comparing imatinib with standard interferon plus low-dose cytarabine." 

N Engl J Med 2002;346:645-652




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