18 januari 2015:

Lees ook: dit artikel: allogene-stamceltransplantatie-met-donor-stamcellen-geeft-langere-recidiefvrije-overleving-en-betere-overall-overleving-bij-patienten-met-npm1-mutatie-van-acute-myeloide-leukemie-aml

17 maart 2011: Bron: N Engl J Med. 2011;364:1027-1036

Mildere dosis van cytarabine geeft nagenoeg zelfde effect op 5 jaarsoverleving en overall overleving bij mensen met AML - Acute myeloide leukemie, maar met minder bijwerkingen en nadelige effecten op langere termijn. Vanmorgen haalde het bericht over deze fase III studie zelfs het ANP en teletekst. Wie even verder kijkt ziet dat de kop in het ANP, nieuw sucesvol medicijn tegen leukemie beetje overdreven is. Cytarabine wordt al heel lang gegeven bij leukemie en vooraf aan stamceltransplantaties bv. Nu heeft een langjarige fase III studie aangetoond dat wanneer AML patienten vantevoren worden gescreend op bepaalde markers (een al of niet monosomal karyotype maakte prognose van aanslaan en kans op genezing verschillend) een veel lagere dosis van de citarabine nodig is voor een zelfde effect. Medscape schrijft daarover een mooi verklarend artikel dat meer recht doet aan de waarde van de studie dan de jubelende perskoppen in Nederland. Al is het wel een belangrijke studie natuurlijk.

Hier enkele citaten uit het artikel van Medscape (onderaan ander artikel over cytarabine uit 2006):

March 16, 2011 — High doses of cytarabine are more effective than conventional doses in inducing relapse-free survival in patients with acute myeloid leukemia (AML). Now, data suggest that an intermediate dose might be just as effective as a high dose, but with less toxicity.

At a median follow-up of 5 years, the authors observed no significant differences between the group receiving intermediate doses and the group receiving high doses of cytarabine. The rates of complete remission were 80% and 82%, respectively; the probability of relapse/event-free survival at 5 years was 34% and 35%; and overall survival was 40% and 42%.

However, treatment with high doses of cytarabine resulted in a greater incidence of grade 3 and 4 toxic events.

.......

The authors compared 2 induction regimens in newly diagnosed AML patients, aged 18 to 60 years, who were randomized to either intermediate- or high-dose therapy. The intermediate-dose group (n = 431) received cytarabine 200 mg/m2 given by continuous intravenous infusion for 24 hours during cycle 1 of induction therapy and 1000 mg/m2 by infusion for 3 hours twice daily during cycle 2 of induction therapy. The high-dose group (n = 429) received a dose-escalated regimen of 1000 mg/m2 cytarabine every 12 hours in cycle 1 and 2000 mg/m2 twice daily in cycle 2.

Patients who achieved a complete response (n = 694) received a third cycle of consolidation chemotherapy or underwent autologous or allogeneic stem cell transplantation.

In the intermediate-dose group, 170 patients relapsed and 260 died (31 in their first complete remission). In the high-dose group, 157 patients relapsed and 251 died (46 in their first complete remission).

At 5 years, there were no significant differences between the 2 groups in terms of event-free or overall survival. The authors note that the cumulative 5-year probabilities for the competing risks for failure after complete remission were similar in the 2 groups (39% vs 37% for relapse, and 7% vs 11% for death during first complete remission). 

There was more toxicity in patients who received the high-dose regimen. The incidence of grade 3 to 4 adverse effects after cycle 1 was greater in the high-dose group than in the intermediate-dose group (61% vs 51%; P = .005).

Lees hier verder artikel uit Medscape

30 juni 2006: Bron: Pediatr Blood Cancer. 2006 Jun 28

Wanneer kinderen met AML = Acute Myeloide Leukemia een paar achter elkaar herhaalde chemokuren krijgen met hoge dosis cytarabine wordt de ziektevrije tijd tot een recidief vergroot en zijn er meer definitieve genezingen. 70% bleek genezen binnen vijf jaar follow-up. Dit blijkt uit twee vergelijkbare studies bij 216 kinderen over een periode van 7 jaar.

RESULTATEN: Het remissie cijfer was 88.8% en mogelijkheid van 5-jaars overleving (OS) en ziektevrije overlevingstijd (EFS) waren respectievelijk 62% (56-69% met 95% Confidence intervals (CIs)) en 56% (49-62%). Behandelingsgerichte sterfte (TRM) was 7.8%. Onder patienten zonder D) met acute promyelocytic leukemie (APL), de aanwezigheid van ( t(8;21) ) of inv(16) was een significant goede prognostische factor, zowel in de univariabele en multivariabele analyses. Kinderen met DS (N = 10) en APL (N = 14) toonden ook een goede overlevingsmogelijkheid: 70% in 5 jaar.

Repetitive cycles of high-dose cytarabine are effective for childhood acute myeloid leukemia: Long-term outcome of the children with AML treated on two consecutive trials of Tokyo children's cancer study group.
Tomizawa D, Tabuchi K, Kinoshita A, Hanada R, Kigasawa H, Tsukimoto I, Tsuchida M. Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.

BACKGROUND: Various methods of intensive chemotherapy have contributed to an improved survival in pediatric acute myeloid leukemia (AML). We here report the long-term results of the two consecutive trials of Tokyo Children's Cancer Study Group (TCCSG), incorporating repetitive use of high-dose cytarabine (HD-Ara-C) based combination chemotherapy in post-remission phase.

PROCEDURE: A total of 216 eligible children with newly diagnosed AML were treated in the two consecutive multi-center trials of TCCSG, M91-13 and M96-14, from August 1991 to September 1998. In M91-13 trial, patients received eight courses of intensive post-remission chemotherapy, including six HD-Ara-C containing courses, after remission-induction therapy. Autologous hematopoietic stem cell transplantation (HSCT) could be selected by physician's choice, and allogeneic HSCT was allocated if donor was available. In M96-14 trial, the last two HD-Ara-C courses were omitted from the chemotherapy arm.

RESULTS: The remission-induction rate was 88.8% and probability of 5-year Overall survival (OS) and event-free survival (EFS) were 62% (56-69% with 95% Confidence intervals (CIs)) and 56% (49-62%), respectively. Treatment-related mortality (TRM) was 7.8%. Among patients without Down syndrome (DS) or acute promyelocytic leukemia (APL), the presence of t(8;21) or inv(16) was a significant good prognostic factor both in the univariate and multivariate analyses. Children with DS (N = 10) and APL (N = 14) also showed a good survival exceeding 70% in 5 years.

CONCLUSIONS: These results suggest that repetitive use of HD-Ara-C was effective and safe for childhood AML. However, further optimization of AML therapy is required. Pediatr Blood Cancer (c) 2006 Wiley-Liss, Inc.

PMID: 16807916 [PubMed - as supplied by publisher]


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