9 januari 2018: lees ook dit artikel: 


9 november 2014: Bron: NEJM - DOI: 10.1056/NEJMoa1403108

FOLFOXIRI  + Bevacizumab (Avastin) geeft in vergelijking met FOLFIRI betere resultaten op progressie vrije tijd 2,4 maanden (van 9,7 naar 12,1 maanden) langere progressie vrije tijd als eerste lijns behandeling bij patiënten met inoperabele uitgezaaide darmkanker. De mediane overall overleving ging van 25,8 naar 31,1 maanden, een "winst" dus van 5,2 maanden. Maar als je ziet wat de bijwerkingen zijn kun je je afvragen of je als patiënt hier blij mee moet zijn. De graad 3/4 bijwerkingen stegen aanzienlijk. Zo steeg het aantal gevallen van neutropenie van 20% naar 50%, diarree van 10,6% naar 18,8%, stomatitis van 4,3% naar 8,8% en peripherale neuropathie van 0% naar 5%. En dat voor 2,4 maanden progressievrije tijd en 5 maanden langer leven?

De studie is uitgevoerd in 34 ziekenhuizen in italië onder leiding van Fotios Loupakis, MD, PhD, van Azienda Ospedaliero-Universitaria Pisana en Universita di Pisa en gepubliceerd in NEJM - The New England Journal of Medicine.

darmkanker beeld van leveruitzaaiing

Foto is een beeld van leveruitzaaiingen uit andere studie


A total of 508 patients were randomly assigned to receive either FOLFIRI plus bevacizumab (control group, n = 256) or FOLFOXIRI plus bevacizumab (experimental group, n = 252). Up to 12 cycles of treatment were administered, followed by 5-FU plus bevacizumab until disease progression. Patients had unresectable metastatic colorectal cancer and had not received chemotherapy or biologic therapy for metastatic disease, although 12.6% had received adjuvant chemotherapy earlier in their disease course.

“Demographic and baseline characteristics of the patients were similar in the two groups,” the investigators noted, “but a higher percentage of patients in the experimental group than in the control group had a primary tumor in the right colon (34.9% vs 23.8%, P = .02).” Among all patients, 79.3% had multiple sites of metastases and 20.7% had disease limited to the liver. The median age was 60 in the FOLFIRI group and 60.5 in the FOLFOXIRI group.

Higher Rates of Grade 3/4 Adverse Events

Grade 3/4 neutropenia occurred in 50% of patients receiving FOLFOXIRI vs 20.5% of patients receiving FOLFIRI. Higher rates with FOLFOXIRI vs FOLFIRI also occurred for several other grade 3/4 adverse events, including diarrhea (18.8% vs 10.6 %), febrile neutropenia (8.8% vs 6.3%), stomatitis (8.8% vs 4.3%) and peripheral neuropathy (5.2% vs 0%). The only grade 3/4 adverse event with a higher incidence reported for FOLFIRI was nausea, but the incidences were low and difference slight.

“The incidence of serious adverse events was similar in the two groups (19.7% in the control group and 20.4% in the experimental group, P = .91),” the researchers stated. “A total of 142 (91.6%) of the deaths in the control group and 121 (92.4%) of the deaths in the experimental group were attributed to disease progression. In each group, a similar number of patients died as a result of adverse events (4 [1.6%] in the control group and 6 [2.4%] in the experimental group).”

Het volledige studierapport: Initial Therapy with FOLFOXIRI and Bevacizumab for Metastatic Colorectal Cancer is tegen betaling verkrijgbaar.

Hier het abstract van deze studie:

FOLFOXIRI plus bevacizumab, as compared with FOLFIRI plus bevacizumab, improved the outcome in patients with metastatic colorectal cancer and increased the incidence of some adverse events.

Initial Therapy with FOLFOXIRI and Bevacizumab for Metastatic Colorectal Cancer

Fotios Loupakis, M.D., Ph.D., Chiara Cremolini, M.D., Gianluca Masi, M.D., Sara Lonardi, M.D., Vittorina Zagonel, M.D., Lisa Salvatore, M.D., Enrico Cortesi, M.D., Gianluca Tomasello, M.D., Monica Ronzoni, M.D., Rosella Spadi, M.D., Alberto Zaniboni, M.D., Giuseppe Tonini, M.D., Angela Buonadonna, M.D., Domenico Amoroso, M.D., Silvana Chiara, M.D., Chiara Carlomagno, M.D., Ph.D., Corrado Boni, M.D., Giacomo Allegrini, M.D., Luca Boni, M.D., and Alfredo Falcone, M.D.

N Engl J Med 2014; 371:1609-1618 DOI: 10.1056/NEJMoa1403108


A fluoropyrimidine plus irinotecan or oxaliplatin, combined with bevacizumab (a monoclonal antibody against vascular endothelial growth factor), is standard first-line treatment for metastatic colorectal cancer. Before the introduction of bevacizumab, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) showed superior efficacy as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI). In a phase 2 study, FOLFOXIRI plus bevacizumab showed promising activity and an acceptable rate of adverse effects.


We randomly assigned 508 patients with untreated metastatic colorectal cancer to receive either FOLFIRI plus bevacizumab (control group) or FOLFOXIRI plus bevacizumab (experimental group). Up to 12 cycles of treatment were administered, followed by fluorouracil plus bevacizumab until disease progression. The primary end point was progression-free survival.


The median progression-free survival was 12.1 months in the experimental group, as compared with 9.7 months in the control group (hazard ratio for progression, 0.75; 95% confidence interval , 0.62 to 0.90; P=0.003). The objective response rate was 65% in the experimental group and 53% in the control group (P=0.006). Overall survival was longer, but not significantly so, in the experimental group (31.0 vs. 25.8 months; hazard ratio for death, 0.79; 95% CI, 0.63 to 1.00; P=0.054). The incidences of grade 3 or 4 neurotoxicity, stomatitis, diarrhea, and neutropenia were significantly higher in the experimental group.


FOLFOXIRI plus bevacizumab, as compared with FOLFIRI plus bevacizumab, improved the outcome in patients with metastatic colorectal cancer and increased the incidence of some adverse events. (Funded by the Gruppo Oncologico Nord Ovest and others; ClinicalTrials.gov number, NCT00719797.)

Presented in part at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, San Francisco, January 24–26, 2013, and at the 48th ASCO Annual Meeting, Chicago, May 31–June 4, 2013.

Supported by the Gruppo Oncologico Nord Ovest and the ARCO Foundation. A research grant was provided by F. Hoffmann–La Roche.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

We thank Drs. Manfredi Morvillo and Roberta Savi for administrative support, Drs. Carlotta Antoniotti and Marta Schirripa for clinical support, and the patients and their families.

Source Information

From Azienda Ospedaliero–Universitaria Pisana and Università di Pisa, Pisa (F.L., C. Cremolini, G.M., L.S., A.F.), Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (S.L., V.Z.), Sapienza Università di Roma (E.C.) and Università Campus Biomedico (G. Tonini), Rome, Azienda Istituti Ospitalieri, Cremona (G. Tomasello), Ospedale San Raffaele, IRCCS, Milan (M.R.), Azienda Ospedaliero–Universitaria Città della Salute e della Scienza, Turin (R.S.), Fondazione Poliambulanza, Brescia (A.Z.), Centro di Riferimento Oncologico, IRCCS, Aviano (A.B.), Ospedale Versilia, Lido di Camaiore (D.A.), Ospedale San Martino, IRCCS, Genoa (S.C.), Azienda Ospedaliera Universitaria Federico II, Naples (C. Carlomagno), Arcispedale Santa Maria Nuova, IRCCS, Reggio Emilia (C.B.), Ospedale Felice Lotti, Pontedera (G.A.), and Azienda Ospedaliero–Universitaria Careggi and Istituto Toscano Tumori, Florence (L.B.) — all in Italy.

Address reprint requests to Dr. Falcone at Azienda Ospedaliero–Universitaria Pisana, Via Roma, 67, 56126 Pisa, Italy, or at .

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