• The efficacy of combined radiation and fluorouracil as adjuvant therapy for pancreatic cancer is suggested by a prospective randomized study conducted by the Gastrointestinal Tumor Study Group (GITSG). Twenty-two patients randomized to no adjuvant treatment and 21 to combined therapy were analyzed. Neither life-threatening toxic reaction nor death due to toxic effect was encountered. The study was terminated prematurely because of an unacceptably low rate of accrual combined with the observation of increasingly large survival differences between the study arms. Median survival for the treatment group (20 months) was significantly longer than that observed for the control group (11 months). Four patients, three in the treated and one in the control group, have survived five years or longer following surgery. The extent of the tumor and initial performance status were significantly and independently related to survival. ( Arch Surg 1985;120:899-903)

Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection.

The incidence of pancreatic cancer still seems to be increasing, and it is the fifth most common cause of cancer death in the United States. The prognosis is one of the most dismal of all cancers: approximately 95% of all patients diagnosed with pancreatic cancer will die within 1 year. 1 To date, the only potentially curative therapy is radical surgical resection. After potentially curative resection for cancer of the pancreatic head, the 1-year survival estimate is 50% to 60%, 2-year survival is 15% to 35%, and 5-year survival is 5% to 20%. In patients with periampullary carcinoma in the ampulla of Vater, distal common bile duct, or duodenum, a much better survival rate is obtained after surgical resection, with a 5-year survival rate of 40% to 60%. 2–7 After radical resection, pancreatic cancer recurs primarily within the abdominal cavity; most failures are locoregional and in the liver. Distant metastases in the lung or peritoneal cavity are seldom seen without local tumor recurrence and are characteristic of late recurrence. Therefore, a treatment approach combining local and systemic adjuvant treatment in pancreas and periampullary cancer seems interesting.

Radiation therapy with or without chemotherapy has been extensively studied in locoregional advanced disease, especially the combination of external radiotherapy combined with 5-fluorouracil (5-FU). 8–11 The possible benefit of chemoradiotherapy resulted in the use of radiotherapy combined with 5-FU as adjuvant treatment in a prospective randomized multicenter study performed by the Gastrointestinal Tumor Study Group (GITSG), in which 14 institutes participated. 12 The high incidence of pancreatic cancer and the relatively large group of participating institutions was intended to guarantee sufficient patient accrual. Radiotherapy consisted of a split course of 40 Gy—two courses of 20 Gy with an interval of 2 weeks. 5-FU was given concomitantly during the first week of radiotherapy and during 2 years thereafter. The 21 patients who received adjuvant treatment had a 2-year survival rate of 43%, significantly better than the 18% found in the control group (p < 0.03). The trial was prematurely closed because the interim analysis showed a statistically significant difference in favor of the treatment arm. Another 30 patients were treated with the same adjuvant treatment and studied by the GITSG with similar results (2-year survival rate 46%). This trial demonstrated for the first time that prolonged survival could be obtained with adjuvant treatment after surgical resection of pancreatic cancer, although this was demonstrated in only a small number of patients. 13 However, a nonrandomized study showed no significant difference in survival after adjuvant treatment as given in the GITSG trial. 14 At present, no other prospective randomized trial in pancreatic or periampullary cancers has been reported in the United States or Europe.

Recently, Yeo et al 15 described the beneficial effect of adjuvant radiotherapy and 5-FU treatment. However, in that nonrandomized study, there seemed to be a selection of patients. Patients who had a satisfactory recovery by postoperative day 60 were encouraged to accept adjuvant therapy. Patients declining radiotherapy were significantly older and had a significantly longer postoperative stay, more intensive care therapy, and a significantly greater incidence of postoperative complications.

The GITSG trial led to the use of standard adjuvant radiotherapy with 5-FU in the United States. In 1987, we initiated a prospective randomized clinical trial in collaboration with the European Organization for Research and Treatment of Cancer (EORTC) to study the effect of adjuvant radiotherapy and 5-FU.

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Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group.

ObjectiveThe survival benefit of adjuvant radiotherapy and 5-fluorouracil versus observation alone after surgery was investigated in patients with pancreatic head and periampullary cancers.Summary Background DataA previous study of adjuvant radiotherapy and chemotherapy in these cancers by the Gastr

Adjuvant Radiotherapy and 5-Fluorouracil After Curative Resection of Cancer of the Pancreas and Periampullary Region

Only women with symptoms need to have their breast implants removed, says government

New, effective therapies are needed for pancreatic ductal adenocarcinoma. Ipilimumab can mediate an immunologic tumor regression in other histologies. This phase II trial evaluated the efficacy of Ipilimumab for advanced pancreatic cancer. Subjects were adults with locally advanced or metastatic pancreas adenocarcinoma with measurable disease, good performance status, and minimal comorbidities. Ipilimumab was administered intravenously (3.0 mg/kg every 3 wk; 4 doses/course) for a maximum of 2 courses. Response rate by response evaluation criteria in solid tumors criteria and toxicity were measured. Twenty-seven subjects were enrolled (metastatic disease: 20 and locally advanced: 7) with median age of 55 years (27 to 68 y) and good performance status (26 with Eastern Cooperative Oncology Group performance status =0 to 1). Three subjects experienced ≥ grade 3 immune-mediated adverse events (colitis:1, encephalitis:1, hypohysitis:1). There were no responders by response evaluation criteria in solid tumors criteria but a subject experienced a delayed response after initial progressive disease. In this subject, new metastases after 2 doses of Ipilimumab established progressive disease. But continued administration of the agent per protocol resulted in significant delayed regression of the primary lesion and 20 hepatic metastases. This was reflected in tumor markers normalization, and clinically significant improvement of performance status. Single agent Ipilimumab at 3.0 mg/kg/dose is ineffective for the treatment of advanced pancreas cancer. However, a significant delayed response in one subject of this trial suggests that immunotherapeutic approaches to pancreas cancer deserve further exploration.

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Phase 2 trial of single agent ipilimumab (Anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma

One-hundred-ninety-four eligible and evaluable patients with histologically confirmed locally unresectable adenocarcinoma of the pancreas were randomly assigned to therapy with high-dose (6000 rads) radiation therapy alone, to moderate-dose (4000 rads) radiation + 5-fluorouracil (5-FU), and to high-dose radiation plus 5-FU. Median survival with radiation alone was only 51/2 months from date of diagnosis. Both 5-FU-containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Forty percent of patients treated with the combined regimens were still living at one year compared with 10% of patients treated with radiation only. Survival differences between 4000 rads plus 5-FU and 6000 rads plus 5-FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819811015%2948%3A8%3C1705%3A%3AAID-CNCR2820480803%3E3.0.CO%3B2-4

Therapy of locally unresectable pancreatic carcinoma: A randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5‐fluorouracil), and high dose radiation + 5‐fluorouracil. The gastrointestinal tumor study group

J. Chaffey

Papers

Therapy of locally unresectable pancreatic carcinoma: A randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5‐fluorouracil), and high dose radiation + 5‐fluorouracil. The gastrointestinal tumor study group