Z Gastroenterol 2007; 45 - V10
DOI: 10.1055/s-2007-988128

Comparable safety and response rate with bevacizumab in combination with capecitabine/oxaliplatin (CapOx/Bev) vs. capecitabine/irinotecan (CapIri/Bev) in advanced CRC (mCRC): A randomized phase II study of the AIO GI study group

A Reinacher-Schick 1, M Geißler 2, U Graeven 3, W Freier 4, S Hegewisch-Becker 5, D Arnold 6, S Kanzler 7, G Dietrich 8, HJ Schmoll 6 W Schmiegel 1, Arbeitsgemeinschaft Internistische Onkologie (AIO), Sektion Kolon, Rektum, Dünndarm
  • 1Ruhr-Universität Bochum, Medizinische Klinik, Bochum, Germany
  • 2Städtische Kliniken, Gastroenterologie, Hepatologie, Onkologie, Esslingen, Germany
  • 3Kliniken Maria-Hilf GmbH, Medizinische Klinik I, Mönchengladbach, Germany
  • 4Onkologische Schwerpunktpraxis, Hildesheim, Germany
  • 5Onkologische Schwerpunktpraxis, Hamburg-Eppendorf, Germany
  • 6Martin – Luther – Universität, Medizinische Klinik IV, Halle, Germany
  • 7Johannes Gutenberg-Universität, Medizinische Klinik I, Mainz, Germany
  • 8Krankenhaus Bietigheim, Innere Medizin I, Bietigheim, Germany

Introduction: Bevacizumab (Bev) combined with 5-FU/FA and both, irinotecan or oxaliplatin are standard regimens for mCRC. Recently, a phase III trial has demonstrated that infusional 5-FU can be substituted by capecitabine (cape) when combined with oxaliplatin and Bev whereas conflicting data are available for feasibility and efficacy of cape/irinotecan combinations.

Aim: This randomized phase II trial was to compare safety and efficacy of Bev with either CapOx or CapIri in untreated mCRC.

Methods: Eligibility criteria: untreated mCRC pts, ECOG PS ≥2, measurable lesion(s), adequate hematologic and organ function. Primary endpoint was % of pts progression-free after 6 months. Treatment plan: Bev 7.5mg/kg day (d)1 with either oxaliplatin (130mg/m2 d1)/cape (1000mg/m2 bid d1–14; CapOx/Bev, arm A) or irinotecan (200mg/m2 d1)/cape (800mg/m2 bid d 1–14; CapIri/Bev, arm B), all q d22. Arm B doses were 20% lower for both, cape and irinotecan, compared to previous trials reporting an unacceptable toxicity profile (Köhne, ASCO 2005). Treatment was continued until progression or unacceptable toxicity.

Results: So far, toxicity data are available on 228 (118/110 pts arm A/B) of total 240 pts. Baseline characteristics (arm A/B): median age 64/65yrs, male 67%/68%. A total of 684/719 cycles (median 6/6 cycles) have been administered. Most common CTC grade 3/4 toxicities(% of pts): Diarrhea 17.0/15.5, hand-foot-syndrome 5.9/2.7, peripheral neuropathy 15.3/0.0. Specific AE's such as thrombosis, 3° hypertension and GI perforation occurred in 3.4/4.5%, 3.4/0.9% and 0.9/0.9% of pts, respectively. Among 185 evaluable pts (96/89), tumor control rates (CR+PR+SD) in arm A/B were 81.4%/82.8%, overall response rates (CR+PR) were 49.0%/52.7%.

Conclusions: Both regimens, CapOx/Bev and CapIri/Bev, are well tolerated without differences in toxicity (except neuropathy). Interestingly, despite the protocol defined dose reduction of CapIri there is seemingly no difference in efficacy as measured by tumor control and response rate. Meanwhile, the trial has finished accrual and data including PFS rate will be presented.