14 augustus 2010: Bron: N Engl J Med. 2010;363:640-652, 653-662.

Minder vaak en minder intensieve bestraling van beginnende lymfklierkanker na chemo geeft zelfde resultaat op ziektevrije tijd en overall overleving maar met minder ernstige bijwerkingen. Mensen met een beginnende vorm van lymfklierkanker - Hodgkin lymfoom, blijken standaard te intensief te worden behandeld met radiotherapie (bestraling) na chemo met het verhoogde risico dat zij op latere leeftijd andere vormen van kanker krijgen en ook ernstig hartfalen. (zie o.a. studie uit 2003 die dit aantoont). Dit blijkt uit een langjarige gerandomiseerde fase III studie en gepubliceerd in N Engl J Med.

Het volledige studierapport: Reduced Treatment Intensity in Patients with Early-Stage Hodgkin's Lymphoma

is gratis in te zien. Onderaan artikel staat abstract plus referentielijst

Ziektevrije overleving vergelijkbaar

De onderzoekers onderzochten 1270 patiënten, gerandomiseerd ingedeeld in vier groepen, met nieuw gediagnosticeerde lymfklierkanker - Hodgkin lymfoom en een gunstige prognose: 4 of 2 cycli van chemo  (ABVD) gevolgd door radiotherapie met 30 GY of 20 Gy  (tabel 1).

Table 1: Reduced Treatment Intensity in Early Hodgkin's Lymphoma

Treatment Group 1 Group 2 Group 3 Group 4
ABVD (cycles) 4 4 2 2
Radiation dose (Gy) 30 20 30 20

ABVD doses: 25 mg/m2 ofdoxorubicin, 10 mg/m2 of bleomycin, 6 mg/m2 of vinblastine, and 375 mg/m2 of dacarbazine


De onderzoekers rapporteren dat patienten in alle 4 de groepen een uitstekend resutlaat letien zien wat betreft ziektevrije tijd en overall overleving na 5 jaar. Na 5 jaar, was de ziektevrije overleving 93% met 4 cycli van ABVD en 91,1% met 2 cycli. Er waren geen significante verschillen in de algehele overleving tussen de 30 Gy en 20 Gy stralingsdoses.

Zoals verwacht, hadden patiënten die 4 cycli van de ABVD hadden gekregen meer bijwerkingen en acute behandelings gerelateerde toxiciteit dan degenen die 2 cycli hadden gekregen (graad 3 of 4 toxiciteit: 51,7% vs 33,2%).

De auteurs concluderen dat "bij patiënten met een lymfoom in een vroeg stadium van Hodgkin en een gunstige prognose, behandeling met 2 cycli van ABVD gevolgd door bestraling met 20 Gy, net zo effectief is en minder toxisch dan 4 cycli van de ABVD gevolgd door bestraling met 30 Gy"

Maar zij waarschuwen dat "gezien het feit dat veel van de late, fatale complicaties van de bestraling pas ontstaan in het tweede decennium na de behandeling, onze gegevens niet kunnen worden gebruikt om het effect van de behandeling op de totale overleving te meten."

"De volgende vraag is of radiotherapie kan worden weggelaten na 2 of 3 cycli van ABVD bij patiënten die [positron emissie tomografie]-negatief zijn. Wij en de [European Organization for Research on Cancer Treatment] voeren grote klinische trials uit om deze vraag te beantwoorden , "zei Dr Engert.

Citaat uit commentaar van Medscape waar u hier het volledige verslag kunt lezen:

 
The researchers report that all 4 regimens produced similar freedom from treatment failure and overall survival. At 5 years, failure-free survival rates were 93% with 4 cycles of ABVD and 91.1% with 2 cycles. There were no significant differences in freedom from treatment failure or overall survival between the 30 Gy and 20 Gy radiation doses.

As expected, patients who had 4 cycles of ABVD had more adverse events and acute treatment-related toxicity than those who had 2 cycles (grade 3 or 4 toxicity: 51.7% vs 33.2%).

The authors conclude that "in patients with early-stage Hodgkin's lymphoma and a favorable prognosis, treatment with 2 cycles of ABVD followed by 20 Gy of involved-field radiation therapy is as effective as, and less toxic than, 4 cycles of ABVD followed by 30 Gy of involved-field radiation therapy."

However, they caution that "given that many of the late, fatal complications of radiation therapy do not emerge until the second decade after treatment, our data cannot speak to the effect of treatment on overall survival."

"The next question is whether radiotherapy can be omitted after 2 or 3 cycles of ABVD in patients who are [positron emission tomography]-negative. We and the [European Organization for Research on Cancer Treatment] are running large clinical trials to answer this question," Dr. Engert said.

 

In patients with early-stage Hodgkin's lymphoma and a favorable prognosis, treatment with two cycles of ABVD followed by 20 Gy of involved-field radiation therapy is as effective as, and less toxic than, four cycles of ABVD followed by 30 Gy of involved-field radiation therapy.

Reduced Treatment Intensity in Patients with Early-Stage Hodgkin's Lymphoma

  • Andreas Engert, M.D.,
  • Annette Plütschow, Ph.D.,
  • Hans Theodor Eich, M.D.,
  • Andreas Lohri, M.D.,
  • Bernd Dörken, M.D.,
  • Peter Borchmann, M.D.,
  • Bernhard Berger, M.D.,
  • Richard Greil, M.D.,
  • Kay C. Willborn, M.D.,
  • Martin Wilhelm, M.D.,
  • Jürgen Debus, M.D.,
  • Michael J. Eble, M.D.,
  • Martin Sökler, M.D.,
  • Antony Ho, M.D.,
  • Andreas Rank, M.D.,
  • Arnold Ganser, M.D.,
  • Lorenz Trümper, M.D.,
  • Carsten Bokemeyer, M.D.,
  • Hartmut Kirchner, M.D.,
  • Jörg Schubert, M.D.,
  • Zdenek Král, M.D.,
  • Michael Fuchs, M.D.,
  • Hans-Konrad Müller-Hermelink, M.D.,
  • Rolf-Peter Müller, M.D.,
  • and Volker Diehl, M.D.*

Abstract

Background

Whether it is possible to reduce the intensity of treatment in early (stage I or II) Hodgkin's lymphoma with a favorable prognosis remains unclear. We therefore conducted a multicenter, randomized trial comparing four treatment groups consisting of a combination chemotherapy regimen of two different intensities followed by involved-field radiation therapy at two different dose levels.

Methods

We randomly assigned 1370 patients with newly diagnosed early-stage Hodgkin's lymphoma with a favorable prognosis to one of four treatment groups: four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy of radiation therapy (group 1), four cycles of ABVD followed by 20 Gy of radiation therapy (group 2), two cycles of ABVD followed by 30 Gy of radiation therapy (group 3), or two cycles of ABVD followed by 20 Gy of radiation therapy (group 4). The primary end point was freedom from treatment failure; secondary end points included efficacy and toxicity of treatment.

Results

The two chemotherapy regimens did not differ significantly with respect to freedom from treatment failure (P=0.39) or overall survival (P=0.61). At 5 years, the rates of freedom from treatment failure were 93.0% (95% confidence interval , 90.5 to 94.8) with the four-cycle ABVD regimen and 91.1% (95% CI, 88.3 to 93.2) with the two-cycle regimen. When the effects of 20-Gy and 30-Gy doses of radiation therapy were compared, there were also no significant differences in freedom from treatment failure (P=1.00) or overall survival (P=0.61). Adverse events and acute toxic effects of treatment were most common in the patients who received four cycles of ABVD and 30 Gy of radiation therapy (group 1).

Conclusions

In patients with early-stage Hodgkin's lymphoma and a favorable prognosis, treatment with two cycles of ABVD followed by 20 Gy of involved-field radiation therapy is as effective as, and less toxic than, four cycles of ABVD followed by 30 Gy of involved-field radiation therapy. Long-term effects of these treatments have not yet been fully assessed. (Funded by the Deutsche Krebshilfe and the Swiss Federal Government; ClinicalTrials.gov number, NCT00265018.)

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