Multicenter phase II trial of adjuvant therapy for resected pancreatic cancer using cisplatin, 5-fluorouracil, and interferon-alfa-2b-based chemoradiation: ACOSOG Trial Z05031

Abstract

Background: The American College of Surgeons Oncology Group sought to confirm the efficacy of a novel interferon-based chemoradiation regimen in a multicenter phase II trial.

Patients and methods: Patients with resected (R0/R1) adenocarcinoma of the pancreatic head were treated with adjuvant interferon-alfa-2b (3 million units s.c. on days 1, 3, and 5 of each week for 5.5 weeks), cisplatin (30 mg/m(2) i.v. weekly for 6 weeks), and continuous infusion 5-fluorouracil (5-FU; 175 mg·m(2)/day for 38 days) concurrently with external-beam radiation (50.4 Gy). Chemoradiation was followed by two 6-week courses of continuous infusion 5-FU (200 mg·m(2)/day). The primary study end point was 18-month overall survival from protocol enrollment (OS18); an OS18 ≥65% was considered a positive study outcome.

Results: Eighty-nine patients were enrolled. Eighty-four patients were assessable for toxicity. The all-cause grade ≥3 toxicity rate was 95% (80 patients) during therapy. No long-term toxicity or toxicity-related deaths were noted. At 36-month median follow-up, the OS18 was 69% [95% confidence interval (CI) 60% to 80%]; the median disease-free survival and overall survival were 14.1 months (95% CI 11.0-20.1 months) and 25.4 months (95% CI 23.4-34.1 months), respectively.

Conclusions: Notwithstanding promising multi-institutional efficacy results, further development of this regimen will require additional modifications to mitigate toxic effects.

Figures

Figure 1.

Treatment schema for American College of Surgeons Oncology Group trial Z05031, a phase II trial of adjuvant interferon-based chemoradiation for patients with resected pancreatic adenocarcinoma. XRT, radiation therapy; i.v.; s.c.; q M, W, F, every Monday, Wednesday, and Friday.

Figure 2.

Kaplan–Meier plot of overall survival (OS) for 80 eligible and assessable patients. The median OS was 25.4 months (95% confidence interval 22.0–32.4 months) from protocol registration (27.1 months from surgery).

Figure 3.

Kaplan–Meier plot of disease-free survival for 80 eligible and assessable patients. The median disease-free survival was 14.1 months (95% confidence interval 11.0–20.1 months) from surgery.