Randomized phase II study of gemcitabine plus radiotherapy versus gemcitabine, 5‐fluorouracil, and cisplatin followed by radiotherapy and 5‐fluorouracil for patients with locally advanced, potentially resectable pancreatic adenocarcinoma

Abstract

Purpose A randomized phase II trial (E1200) was designed to assess toxicities and surgical resection rates in two neoadjuvant gemcitabine-based chemoradiation regimens in patients with borderline resectable pancreatic cancer. The trial was terminated early due to poor accrual. Patients and Methods Patients with borderline resectable adenocarcinomas of the pancreas were enrolled. Arm A patients (n=10) received gemcitabine 500mg/m2 q6 weeks, with radiation to 50.4Gy followed by surgical resection. Arm B patients (n=11) received preoperative gemcitabine 175mg/m2 on days 1, 5, 29, and 33, cisplatin 20mg/m2 on days 1-5 and 29-32, 5-FU 600mg/m2 on days 1-5 and 29-32, followed by radiation with continuous infusion 5-FU 225mg/m2 for 6 weeks. All patients received adjuvant gemcitabine 1000 mg/m2 weekly × 3 for five cycles. Results 3 patients in arm A, and 2 patients in arm B were resected. Hematologic toxicity was comparable between the two arms except more patients in arm B developed grade 3 or 4 thrombocytopenia than those in arm A. Arm B had fewer grade 1-2 GI toxicities although more patients (45%) experienced grade 3-4 GI toxicity. Conclusions This phase II trial showed that both regimens were tolerable, and resectability and survival were comparable to previous studies.

Percutaneous Radiofrequency Ablation of Unresectable Locally Advanced Pancreatic Cancer: Preliminary Results

“…The efficacy of neoadjuvant therapy as a bridge to potential curative resection is broad, ranging from 3% to 79%. [9][10][11][12] Standard systemic chemotherapy for unresectable pancreatic cancer is usually gemcitabine based. 13 Recently, new chemotherapy drugs and combination have shown significantly better response rates and survival than gemcitabine in patients who have a good performance status, and trials of this regimen in the neoadjuvant setting are ongoing.…”

Novel Thiosemicarbazone Iron Chelators Induce Up-Regulation and Phosphorylation of the Metastasis Suppressor N-myc Down-Stream Regulated Gene 1: A New Strategy for the Treatment of Pancreatic Cancer

“…Since then, iron chelators designed specifically for the treatment of cancer have been developed with the thiosemicarbazone 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP; Fig. 1D), entering a wide variety of phase I and II clinical trials (Landry et al, 2010). However, the latter agent has shown considerable problems, including low efficacy and serious side effects, including methemoglobinemia and hypoxia (Kalinowski and Richardson, 2005).…”

Borderline Resectable Pancreatic Cancer: What Have We Learned and Where Do We Go From Here?

“…Indeed, since the premature closure in 2005 of Eastern Cooperative Oncology Group Trial 1200, the first national trial dedicated to the study of borderline resectable PDAC, no data from prospective trials have been generated to guide the evaluation or management of patients with this stage of disease. 6 Given this historical context and the recognized need for improved standardization and quality control in multi-institutional clinical trials for pancreatic cancer, we must ask: How do we incorporate what we have learned thus far into the design of future prospective clinical trials, and what questions need to be answered before we take the critical next step to characterize this challenging group of patients?…”