Researchers affiliated with the European Study Group for Pancreatic Cancer have reported a survival advantage for adjuvant chemotherapy but not for adjuvant chemoradiotherapy for resected pancreatic cancer. The results of this trial were published in the March 18, 2004 issue of The New England Journal of Medicine. ^1,2

Approximately 15% of patients with pancreatic cancer will have localized disease amenable to surgical resection. Following adjuvant 5-FU-based chemoradiation, the median survival for patients with localized pancreatic cancer is 16-21 months as reported from the GITSG trial, ³ and several large phase III trials from Europe. ^4,5 In addition, adjuvant 5-FU-based chemoradiation has produced 2-year and 5-year overall survival rates of 40% and 20%, respectively. Methods to improve survival in patients with resectable pancreatic cancer include:

• Use of pre-operative (neoadjuvant) chemoradiation. ⁶
• Use of chemotherapy as a sole or primary adjuvant agent. ⁷
• Altered chemoradiation programs, either by utilizing the profound radiosensitization properties of Gemzar®. ^8,9
• Adding additional agents to 5-FU. ^10,4 modification of postchemoradiation chemotherapy.

It is generally accepted that radiation combined with chemotherapy is better than either alone for adjuvant therapy of pancreatic cancer.

In the recent European study, the researchers concluded that adjuvant chemotherapy had a beneficial effect while chemoradiotherapy did not and was possibly detrimental. Patients with resected pancreatic cancer were randomly allocated to the following groups:

• Observational control group (69),
• Chemoradiotherapy consisting of 5-FU given during radiation(75),
• Chemotherapy consisting of 5-FU/LV given after radiation therapy or surgery (75),
• Chemoradiotherapy and chemotherapy (72).

This study had a median follow-up of 47 months, at which time 82% of the patients had died. They apparently did not have enough patients to analyze the 4 separate groups so they compared chemoradiotherapy with no chemoradiaotherapy (n=145) and reported that the no chemoradiotherapy group had a 20% 5-year survival compared to 10% for those who received chemoradiotherapy. They also compared those who received adjuvant chemotherapy versus those who did not (n=147) and reported a 21% survival for those receiving chemotherapy versus 8% for those who did not. Patients given chemoradiotherapy alone had a worse outcome than those who received no adjuvant therapy. The authors suggest that chemoradiotherapy delayed the administration of adjuvant chemotherapy but this does not explain why chemoradiotherapy was worse than nothing.

Comments: This study is puzzling in that most studies have suggested a beneficial effect of concomitant radiation and chemotherapy for adjuvant treatment of pancreatic cancer and several studies are ongoing which evaluate additional chemotherapy after chemoradiotherapy. However, these results appear to question the role of radiation therapy in the adjuvant treatment of pancreatic cancer.

References

1. Neoptolemos JP, Stocken DD, Friess H, et al. A Randomized Trial of Chemoradiotherapy and Chemotherapy after Resection of Pancreatic Cancer. The New England Journal of Medicine 2004; 350:1200-1210.

2. Choti MA, et al. Editorial: Adjuvant Therapy for Pancreatic Cancer. The New England Journal of Medicine 2004; 350:1249-1251.

3. Gastrointestinal Tumor Study Group: Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer 1987;59: 2006-2010.

4. Klinkenbijl JH, Jeekel J, Sahmoud T et.al: Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: Phase III trial of the EORTC gastrointestinal tract cooperative group. Ann Surg 1999;230: 776-782.

5. Neoptolemos JP, Dunn JA, Stocken DD, et.al: Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: A randomized controlled trial. Lancet 2001;358: 1576-1585.

6. Mornex FM, Ychou M, Bossard N, et al.: Preoperative concurrent chemoradiation in resectable pancreatic cancer: The French Phase II Trial FFCD 9704-SFRO. Proc Amer Soc Clin Oncol 2003. Abstract #1165.

7. Villa E, Bonetto E, Panucci MG, et al.: A pilot trial of a PEFG regimen after surgery for pancreatic adenocarcinoma (PA). Proc Amer Soc Clin Oncol 2003. Abstract #1124.

8. Blackstock AW, Tepper J, Kachnic L, et al.: Adjuvant gemcitabine and concurrent radiation for resected pancreatic cancer: A phase II study. Proc Amer Soc Clin Oncol 2003. Abstract #1069.

9. Anne D, Marc P, Tom B, et al.: Adjuvant gemcitabine (GEM) and concurrent continuous radiation (45Gy) for resected pancreatic head carcinoma: A multicenter belgian phase II study. Proc Amer Soc Clin Oncol 2003. Abstract #1133.

10. Picozzi VJ, Kozarek RE, Jacobs AD, et al.: Adjuvant therapy for resected pancreas cancer (PC) using alpha-interferon (IFN)-based chemoradiation: Completion of a phase II trial. Proc Amer Soc Clin Oncol 2003. Abstract #1061.