4012 Background: Overall survival (OS) in phase III studies with 1st line combination therapy in ACC may be influenced by imbalances in salvage treatments. This is the first study that prospectively investigates the sequential vs the combined use of all available effective cytotoxic drugs. Methods: Previously untreated patients (pts), WHO PS 0–2 were randomized between 1st line capecitabine (Cap), 2nd line irinotecan (Iri), and 3rd line Cap + oxaliplatin (CapOx) (Arm A, sequential) vs 1st line CapIri and 2nd line CapOx (Arm B, combination). The dose of Cap was 1250 mg/m2 (mono) or 1,000 mg/m2 (combination) b.i.d. day 1–14, Iri 350 mg/m2 (mono) or 250 mg/m2 (combination), and Ox 130 mg/m2. All cycles were q 3 weeks with Iri/Ox given i.v. on day 1. Response was assessed q 3 cycles. Primary endpoint was OS. The study was designed to detect a 20% reduction in the hazard of death (HR=0.80) for an increase in median OS from 14 to 17.5 months (a=0.05, 2-tailed test). Results: 820 pts were randomized between Jan ‘03 and Dec ‘04 in 74 Dutch hospitals. Of 804 eligible pts, 796 received = 1 cycle. Median age was 63 (27–84) yrs, median WHO PS 0 (0–2), median follow-up 32 months. Pts (n) in arm A: 398 (1st line), 248 (2nd line), 141 (3rd line); arm B: 398 (1st line), 210 (2nd line). Median OS in arm A was 16.3 months (95%CI 14.3–18.2) and in arm B 17.7 months (95%CI 15.2–19.4), logrank p=0.2. Overall gr 3–4 toxicity over all lines did not differ significantly except for gr 3 hand-foot syndrome (HFS) (13% in A and 6% in B, p=0.0009). Death was probably related to treatment in 11 pts (neutropenic sepsis and/or diarrhea, 8 arm A, 3 arm B) and involved protocol violations in some. In 1st line significant differences in gr 3–4 toxicity in arm A vs arm B were diarrhea (10% vs 25%, p<0.0001), febrile neutropenia (1% vs 6%, p=0.0001) and HFS (12% vs 5%, p=0.0004). All-cause 60-day mortality was 3.0% (n=12) in arm A and 4.5% (n=18) in arm B. Updated results will be presented at the meeting, including data on QoL (EORTC QLQ C30). Conclusions: Combination therapy does not significantly improve OS compared with sequential therapy. Both treatment strategies are valid options for pts with ACC. No significant financial relationships to disclose.
Treatment strategies in colorectal cancer patients with initially unresectable liver-only metastases, a study protocol of the randomised phase 3 CAIRO5 study of the Dutch Colorectal Cancer Group (DCCG)
