No abstract

Purpose A multi-institutional phase II trial assessed the utility of dose-painted IMRT (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% as compared to the conventional radiation/5FU/MMC arm from RTOG 9811. Methods and Materials T2-4N0-3M0 anal cancer patients received 5FU and MMC days 1 and 29 of DP-IMRT, prescribed per stage - T2N0: 42Gy elective nodal and 50.4Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3: 45Gy elective nodal, 50.4Gy ≤ 3cm or 54Gy > 3cm metastatic nodal and 54Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator’s ability to perform DP-IMRT. Results Of 63 accrued patients, 52 were evaluable. Tumor stage included: 54% II, 25% IIIA, 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=0.032), grade 3+ gastrointestinal, 21% (9811 36%, P=0.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<0.0001) with DP-IMRT. On initial pre-treatment review, 81% required DP-IMRT re-planning, while final review revealed only three cases with normal tissue major deviations. Conclusions Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic, and grade 3+ dermatologic and gastrointestinal toxicity. While DP-IMRT proved feasible, the high pre-treatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials.

Context Among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil. Objective To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma. Design, Setting, and Participants Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18, 2006, at 164 US and Canadian institutions. Intervention Chemotherapy with either fluorouracil (continuous infusion of 250 mg/m 2 per day; n=230) or gemcitabine (30-minute infusion of 1000 mg/m 2 once per week; n=221) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil (250 mg/m 2 per day) was the same for all patients (50.4 Gy). Main Outcome Measures Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity. Results A total of 451 patients were randomized, eligible, and analyzable. Patients with pancreatic head tumors (n=388) had a median survival of 20.5 months and a 3-year survival of 31% in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22% in the fluorouracil group (hazard ratio, 0.82 [95% confidence interval, 0.65-1.03]; P=.09). The treatment effect was strengthened on multivariate analysis (hazard ratio, 0.80 [95% confidence interval, 0.63-1.00]; P=.05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in the gemcitabine group (PϽ.001) without a difference in febrile neutropenia or infection. There were no differences in the ability to complete chemotherapy or radiation therapy (Ͼ85%). Conclusions The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant. Trial Registration clinicaltrials.gov Identifier: NCT00003216

The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine.