Pancreatic Cancer

Summary Type: Treatment
Summary Audience: Health professionals
Summary Language: English
Summary Description: Expert-reviewed information summary about the treatment of pancreatic cancer.

Pancreatic Cancer

General Information

Note: Information on pancreatic cancer in children is available in the PDQ summary on Unusual Cancers of Childhood.

Note: Estimated new cases and deaths from pancreatic cancer in the United States in 2007:^1,

• New cases: 37,170.
• Deaths: 33,370.

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Carcinoma of the pancreas has a markedly increased incidence over the past several decades and ranks as the fourth leading cause of cancer death in the United States. Despite the high mortality rate associated with pancreatic cancer, its etiology is poorly understood.² Cancer of the exocrine pancreas is rarely curable and has an overall survival (OS) rate of less than 4%.³ The highest cure rate occurs if the tumor is truly localized to the pancreas; however, this stage of the disease accounts for fewer than 20% of cases. For those patients with localized disease and small cancers (<2 cm) with no lymph node metastases and no extension beyond the capsule of the pancreas, complete surgical resection can yield actuarial 5-year survival rates of 18% to 24%.^4,[Level of evidence: 3iA] Improvements in imaging technology, including spiral computed tomographic scans, magnetic resonance imaging scans, positron emission tomographic scans, endoscopic ultrasound examination, and laparoscopic staging can aid in the diagnosis and the identification of patients with disease that is not amenable to resection.⁵ In a case series of 228 patients, positive peritoneal cytology had a positive predictive value of 94%, specificity of 98%, and sensitivity of 25% for determining unresectability.⁶ For patients with advanced cancers, the OS rate of all stages is less than 1% at 5 years with most patients dying within 1 year.^7,8,9,10

No tumor-specific markers exist for pancreatic cancer; markers such as serum CA 19-9 have low specificity. Most patients with pancreatic cancer will have an elevated CA 19-9 at diagnosis. Following or during definitive therapy, the increase of CA 19-9 levels may identify patients with progressive tumor growth.^11,[Level of evidence: 3iDii] The presence of a normal CA 19-9, however, does not preclude recurrence.

Patients with any stage of pancreatic cancer can appropriately be considered candidates for clinical trials because of the poor response to chemotherapy, radiation therapy, and surgery as conventionally used. Palliation of symptoms, however, may be achieved with conventional treatment. Symptoms caused by pancreatic cancer may depend on the site of the tumor within the pancreas and the degree of involvement. Palliative surgical or radiologic biliary decompression, relief of gastric outlet obstruction, and pain control may improve the quality of life while not affecting OS.^12,13 Palliative efforts may also be directed to the potentially disabling psychological events associated with the diagnosis and treatment of pancreatic cancer.^14, Information about ongoing clinical trials is available from the NCI Web site.

¹ American Cancer Society.: Cancer Facts and Figures 2007. Atlanta, Ga: American Cancer Society, 2007. Also available online. Last accessed March 5, 2007.

² Silverman DT, Schiffman M, Everhart J, et al.: Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer. Br J Cancer 80 (11): 1830-7, 1999.

³ Greenlee RT, Murray T, Bolden S, et al.: Cancer statistics, 2000. CA Cancer J Clin 50 (1): 7-33, 2000 Jan-Feb.

⁴ Yeo CJ, Abrams RA, Grochow LB, et al.: Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 225 (5): 621-33; discussion 633-6, 1997.

⁵ Riker A, Libutti SK, Bartlett DL: Advances in the early detection, diagnosis, and staging of pancreatic cancer. Surg Oncol 6 (3): 157-69, 1997.

⁶ Merchant NB, Conlon KC, Saigo P, et al.: Positive peritoneal cytology predicts unresectability of pancreatic adenocarcinoma. J Am Coll Surg 188 (4): 421-6, 1999.

⁷ Lillemoe KD: Current management of pancreatic carcinoma. Ann Surg 221 (2): 133-48, 1995.

⁸ Yeo CJ: Pancreatic cancer: 1998 update. J Am Coll Surg 187 (4): 429-42, 1998.

⁹ Nitecki SS, Sarr MG, Colby TV, et al.: Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving? Ann Surg 221 (1): 59-66, 1995.

¹⁰ Conlon KC, Klimstra DS, Brennan MF: Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg 223 (3): 273-9, 1996.

¹¹ Willett CG, Daly WJ, Warshaw AL: CA 19-9 is an index of response to neoadjunctive chemoradiation therapy in pancreatic cancer. Am J Surg 172 (4): 350-2, 1996.

¹² Sohn TA, Lillemoe KD, Cameron JL, et al.: Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J Am Coll Surg 188 (6): 658-66; discussion 666-9, 1999.

¹³ Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.

¹⁴ Passik SD, Breitbart WS: Depression in patients with pancreatic carcinoma. Diagnostic and treatment issues. Cancer 78 (3 Suppl): 615-26, 1996.

Cellular Classification

Pancreatic cancer includes the following carcinomas:

Malignant
• Duct cell carcinoma (90% of all cases).
• Acinar cell carcinoma.
• Papillary mucinous carcinoma.
• Signet ring carcinoma.
• Adenosquamous carcinoma.
• Undifferentiated carcinoma.
• Mucinous carcinoma.
• Giant cell carcinoma.
• Mixed type (ductal-endocrine or acinar-endocrine).
• Small cell carcinoma.
• Cystadenocarcinoma (serous and mucinous types).
• Unclassified.
• Pancreatoblastoma.
• Papillary-cystic neoplasm (Frantz tumor). (This tumor has lower malignant potential and may be cured with surgery alone.)^1,2,
• Invasive adenocarcinoma associated with cystic mucinous neoplasm or intraductal papillary mucinous neoplasm.

Borderline Malignancies
• Mucinous cystic tumor with dysplasia.
• Intraductal papillary mucinous tumor with dysplasia.^3,
• Pseudopapillary solid tumor.

¹ Sanchez JA, Newman KD, Eichelberger MR, et al.: The papillary-cystic neoplasm of the pancreas. An increasingly recognized clinicopathologic entity. Arch Surg 125 (11): 1502-5, 1990.

² Warshaw AL, Compton CC, Lewandrowski K, et al.: Cystic tumors of the pancreas. New clinical, radiologic, and pathologic observations in 67 patients. Ann Surg 212 (4): 432-43; discussion 444-5, 1990.

³ Sohn TA, Yeo CJ, Cameron JL, et al.: Intraductal papillary mucinous neoplasms of the pancreas: an increasingly recognized clinicopathologic entity. Ann Surg 234 (3): 313-21; discussion 321-2, 2001.

Stage Information

The staging system for pancreatic exocrine cancer continues to evolve. The importance of staging beyond that of resectable and unresectable is uncertain since state-of-the-art treatment has demonstrated little impact on survival. To communicate a uniform definition of disease, however, knowledge of the extent of the disease is necessary. Cancers of the pancreas are commonly identified by the site of involvement within the pancreas. Surgical approaches differ for masses in the head, body, tail, or uncinate process of the pancreas.

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification.^1,

TNM Definitions

Primary tumor (T)
• TX: Primary tumor cannot be assessed
• T0: No evidence of primary tumor
• Tis: Carcinoma in situ
• T1: Tumor is limited to the pancreas and is 2 cm or less in greatest dimension
• T2: Tumor is limited to the pancreas and is more than 2 cm in greatest dimension
• T3: Tumor extends beyond the pancreas but without involvement of the celiac axis or the superior mesenteric artery
• T4: Tumor involves the celiac axis or the superior mesenteric artery (unresectable primary tumor)

Regional lymph nodes (N)
• NX: Regional lymph nodes cannot be assessed
• N0: No regional lymph node metastasis
• N1: Regional lymph node metastasis

Distant metastasis (M)
• MX: Distant metastasis cannot be assessed
• M0: No distant metastasis
• M1: Distant metastasis

AJCC Stage Groupings

Stage 0
• Tis, N0, M0

Stage IA
• T1, N0, M0

Stage IB
• T2, N0, M0

Stage IIA
• T3, N0, M0

Stage IIB
• T1, N1, M0
• T2, N1, M0
• T3, N1, M0

Stage III
• T4, any N, M0

Stage IV
• Any T, any N, M1

¹ Exocrine pancreas. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 157-164.

Treatment Option Overview

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

The survival rate of patients with any stage of pancreatic exocrine cancer is poor. Clinical trials are appropriate alternatives for treatment of patients with any stage of disease and should be considered prior to selecting palliative approaches. To provide optimal palliation, determination of resectability must be made. Staging studies for resectability include helical computed tomographic scan, magnetic resonance imaging scan, and endoscopic ultrasound. The introduction of minimally invasive techniques, such as laparoscopy and laparoscopic ultrasound, may decrease the use of laparotomy.^1,2 Surgical resection remains the primary modality when feasible since, on occasion, resection can lead to long-term survival and provides effective palliation.^3,4,5,[Level of evidence: 3iA] Frequently, malabsorption caused by exocrine insufficiency contributes to malnutrition. Attention to pancreatic enzyme replacement can help alleviate this problem. (Refer to the PDQ summary on Nutrition in Cancer Care for more information.) Celiac axis (and intrapleural) nerve blocks can provide highly effective and long-lasting control of pain for some patients. Information about ongoing clinical trials is available from the NCI Web site .

The designations in PDQ that treatments are “standard” or “under clinical evaluation” are not to be used as a basis for reimbursement determinations.

¹ John TG, Greig JD, Carter DC, et al.: Carcinoma of the pancreatic head and periampullary region. Tumor staging with laparoscopy and laparoscopic ultrasonography. Ann Surg 221 (2): 156-64, 1995.

² Minnard EA, Conlon KC, Hoos A, et al.: Laparoscopic ultrasound enhances standard laparoscopy in the staging of pancreatic cancer. Ann Surg 228 (2): 182-7, 1998.

³ Yeo CJ, Cameron JL, Lillemoe KD, et al.: Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg 221 (6): 721-31; discussion 731-3, 1995.

⁴ Conlon KC, Klimstra DS, Brennan MF: Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg 223 (3): 273-9, 1996.

⁵ Yeo CJ, Abrams RA, Grochow LB, et al.: Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 225 (5): 621-33; discussion 633-6, 1997.

Stage I Pancreatic Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Approximately 20% of patients present with pancreatic cancer amenable to local surgical resection, with operative mortality rates of approximately 1% to 16%.^1,2,3,4,5 Using information from the Medicare claims database, a national cohort study of over 7,000 patients undergoing pancreaticoduodenectomy between 1992 and 1995 revealed higher in-hospital mortality rates at low-volume hospitals (<1 pancreaticoduodenectomy per year) versus high-volume hospitals (>5 per year)(16% vs. 4% respectively, P <.01).¹ Complete resection can yield 5-year survival rates of 18% to 24%, but ultimate control remains poor because of the high incidence of both local and distant tumor recurrence.^6,7,8,[Level of evidence: 3iA] The role of postoperative therapy in the management of this disease is inadequately defined because limited randomized clinical trial data are available to support the use of postoperative therapy in patients with resected pancreatic cancer.^{9,10,11,12,13} These trials are statistically underpowered and provide conflicting results.

A small randomized trial conducted by the Gastrointestinal Study Group (GITSG) in 1985 demonstrated a significant but modest improvement in median-term and long-term survival over resection alone with postoperative bolus 5-fluorouracil (5-FU) and regional split course radiation given at a dose of 40 Gy.^9,[Level of evidence: 1iiA];^10,[Level of evidence: 2A] An attempt by the European Organization for the Research and Treatment of Cancer to reproduce the results of the GITSG trial failed to confirm a significant benefit for adjuvant chemoradiation (CRT) over resection alone;^11,[Level of evidence: 1iiA] however, this trial treated patients with pancreatic as well as periampullary cancers (with a potential better prognosis). A subset analysis of the patients with primary pancreatic tumors indicated a trend towards improved median, 2-year, and 5-year overall survival with adjuvant therapy compared with surgery alone (17.1 months, 37% and 20% vs. 12.6 months, 23% and 10%, P = .09 for median survival). An updated analysis of a subsequent European Study for Pancreatic Cancer (ESPAC 1) trial that examined only patients who underwent strict randomization following pancreatic resection to one of four groups (i.e., observation, chemotherapy, CRT or CRT followed by additional chemotherapy), with a 2 × 2 factorial design reported, at a median follow-up of 47 months, a survival benefit for only the patients who received postoperative chemotherapy. These results were difficult to interpret, however, because of a high rate of protocol nonadherence.^12,13,14,[Level of evidence: 1iiA] Additional trials are still warranted to determine effective adjuvant therapy for this disease.

Further phase I and phase II clinical trials exploring other local and systemic combination adjuvant therapies such as preoperative CRT, CRT with protracted infusion 5-FU or the addition of mitomycin-C, CRT with elective hepatic radiation therapy, intra-arterial CRT, and CRT with intraoperative radiation or high-dose standard radiation therapy have failed to produce significant improvements in survival over historical controls with postoperative 5-FU and 50.4 Gy radiation therapy.^{15,16,17,18,19,}

Standard treatment options:

1. Radical pancreatic resection:
   • Whipple procedure (pancreaticoduodenal resection).
   • Total pancreatectomy when necessary for adequate margins.
   • Distal pancreatectomy for tumors of the body and tail of the pancreas.^20,21,
2. Radical pancreatic resection with or without postoperative 5-FU chemotherapy and radiation therapy.^{9,10,11,12,13,}

Treatment options under clinical evaluation:

1. For patients with resected tumors, postoperative radiation therapy with other chemotherapeutic agents. In 2002, the Radiation Therapy Oncology Group completed a prospective, multicenter randomized trial to evaluate whether gemcitabine chemotherapy administered before and following radiation with concurrent 5-FU is superior to adjuvant 5-FU for patients with completely resected tumors; preliminary analysis is pending.²² Information about ongoing clinical trials is available from the NCI Web site.
2. For patients with resected tumors, postoperative chemotherapy alone. The European Study for Pancreatic Cancer (ESPAC-3) trial is ongoing to evaluate postoperative chemotherapy with either 5-FU/leucovorin or gemcitabine versus no additional treatment.^23,

¹ Birkmeyer JD, Finlayson SR, Tosteson AN, et al.: Effect of hospital volume on in-hospital mortality with pancreaticoduodenectomy. Surgery 125 (3): 250-6, 1999.

² Cameron JL, Pitt HA, Yeo CJ, et al.: One hundred and forty-five consecutive pancreaticoduodenectomies without mortality. Ann Surg 217 (5): 430-5; discussion 435-8, 1993.

³ Spanknebel K, Conlon KC: Advances in the surgical management of pancreatic cancer. Cancer J 7 (4): 312-23, 2001 Jul-Aug.

⁴ Balcom JH 4th, Rattner DW, Warshaw AL, et al.: Ten-year experience with 733 pancreatic resections: changing indications, older patients, and decreasing length of hospitalization. Arch Surg 136 (4): 391-8, 2001.

⁵ Sohn TA, Yeo CJ, Cameron JL, et al.: Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg 4 (6): 567-79, 2000 Nov-Dec.

⁶ Cameron JL, Crist DW, Sitzmann JV, et al.: Factors influencing survival after pancreaticoduodenectomy for pancreatic cancer. Am J Surg 161 (1): 120-4; discussion 124-5, 1991.

⁷ Yeo CJ, Cameron JL, Lillemoe KD, et al.: Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg 221 (6): 721-31; discussion 731-3, 1995.

⁸ Yeo CJ, Abrams RA, Grochow LB, et al.: Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 225 (5): 621-33; discussion 633-6, 1997.

⁹ Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer 59 (12): 2006-10, 1987.

¹⁰ Kalser MH, Ellenberg SS: Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120 (8): 899-903, 1985.

¹¹ 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 cancer cooperative group. Ann Surg 230 (6): 776-82; discussion 782-4, 1999.

¹² Neoptolemos JP, Dunn JA, Stocken DD, et al.: Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 358 (9293): 1576-85, 2001.

¹³ Neoptolemos JP, Stocken DD, Friess H, et al.: A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350 (12): 1200-10, 2004.

¹⁴ Choti MA: Adjuvant therapy for pancreatic cancer--the debate continues. N Engl J Med 350 (12): 1249-51, 2004.

¹⁵ Tepper JE, Noyes D, Krall JM, et al.: Intraoperative radiation therapy of pancreatic carcinoma: a report of RTOG-8505. Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 21 (5): 1145-9, 1991.

¹⁶ Whittington R, Neuberg D, Tester WJ, et al.: Protracted intravenous fluorouracil infusion with radiation therapy in the management of localized pancreaticobiliary carcinoma: a phase I Eastern Cooperative Oncology Group Trial. J Clin Oncol 13 (1): 227-32, 1995.

¹⁷ Hoffman JP, Lipsitz S, Pisansky T, et al.: Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group Study. J Clin Oncol 16 (1): 317-23, 1998.

¹⁸ Evans DB, Abbruzzese JL, Cleary KR, et al.: Preoperative chemoradiation for adenocarcinoma of the pancreas: excessive toxicity of prophylactic hepatic irradiation. Int J Radiat Oncol Biol Phys 33 (4): 913-8, 1995.

¹⁹ Thomas CR Jr, Weiden PL, Traverso LW, et al.: Concomitant intraarterial cisplatin, intravenous 5-flourouracil, and split-course radiation therapy for locally advanced unresectable pancreatic adenocarcinoma: a phase II study of the Puget Sound Oncology Consortium (PSOC-703). Am J Clin Oncol 20 (2): 161-5, 1997.

²⁰ Dalton RR, Sarr MG, van Heerden JA, et al.: Carcinoma of the body and tail of the pancreas: is curative resection justified? Surgery 111 (5): 489-94, 1992.

²¹ Brennan MF, Moccia RD, Klimstra D: Management of adenocarcinoma of the body and tail of the pancreas. Ann Surg 223 (5): 506-11; discussion 511-2, 1996.

²² Regine WF, Radiation Therapy Oncology Group: Phase III Randomized Study of Adjuvant Fluorouracil-Based Chemoradiotherapy Preceded and Followed By Fluorouracil Versus Gemcitabine in Patients With Resected Adenocarcinoma of the Pancreas, RTOG-9704, Clinical trial, Closed.

²³ ESPAC-3(v2) Phase III Adjuvant Trial in Pancreatic Cancer Comparing 5FU and D-L-Folinic Acid vs. Gemcitabine. Leeds, UK: National Cancer Research Network Trials Portfolio, 2004. Available online. Last accessed May 5, 2006.

Stage IIA Pancreatic Cancer

Some patients with stage IIA pancreatic cancer whose tumors are technically unresectable should be considered for participation in clinical trials.¹ These patients may benefit from palliation of biliary obstruction by endoscopic, surgical, or radiological means.² Although some data demonstrate a survival advantage associated with combined chemotherapy and radiation therapy for patients with locally advanced unresectable disease,^3,4,5 patients with unresectable pancreatic cancer should be considered for participation in clinical trials.

Pain associated with unresectable pancreatic cancer may be palliated with radiation therapy, with or without chemotherapy,^3,4,5,6 or with chemical splanchnicectomy with 50% alcohol at the time of surgical exploration.⁷ Celiac nerve blocks and local neurosurgical procedures to relieve pain can be considered.^8,

Standard treatment options:

1. Pancreatectomy when feasible, with or without adjuvant fluorouracil (5-FU) chemotherapy and radiation therapy.^{9,10,11,12,13,}
2. Radiation therapy with 5-FU chemotherapy for patients with locally unresectable disease.^3,4,5,
3. Palliative surgical biliary bypass, percutaneous radiologic biliary stent placement, or endoscopic biliary stent placement.^7,14,

Treatment options under clinical evaluation:

1. For patients with resected tumors, postoperative radiation therapy with other chemotherapeutic agents. In 2002, the Radiation Therapy Oncology Group completed a prospective, multicenter randomized trial to evaluate whether gemcitabine chemotherapy administered prior to and following radiation with concurrent 5-FU is superior to adjuvant 5-FU for patients with completely resected tumors; preliminary analysis is pending.^15,
2. For patients with resected tumors, postoperative chemotherapy alone. The ESPAC-3 trial is ongoing to evaluate postoperative chemotherapy with either 5-FU/leucovorin or gemcitabine versus no additional treatment.¹⁶
3. For patients with technically unresectable tumors, biologic agents in combination with radiation and/or chemotherapy.^17,
4. For patients with locally unresectable tumors, preoperative radiation therapy with various chemotherapeutic agents and/or radiosensitizers is under clinical evaluation.
5. Intraoperative radiation therapy and/or implantation of radioactive sources is another treatment option.^6,18,

Information about ongoing clinical trials is available from the NCI Web site.

¹ Pingpank JF, Hoffman JP, Ross EA, et al.: Effect of preoperative chemoradiotherapy on surgical margin status of resected adenocarcinoma of the head of the pancreas. J Gastrointest Surg 5 (2): 121-30, 2001 Mar-Apr.

² Sohn TA, Lillemoe KD, Cameron JL, et al.: Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J Am Coll Surg 188 (6): 658-66; discussion 666-9, 1999.

³ Moertel CG, Frytak S, Hahn RG, et al.: 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. Cancer 48 (8): 1705-10, 1981.

⁴ Whittington R, Solin L, Mohiuddin M, et al.: Multimodality therapy of localized unresectable pancreatic adenocarcinoma. Cancer 54 (9): 1991-8, 1984.

⁵ Moertel CG, Childs DS Jr, Reitemeier RJ, et al.: Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet 2 (7626): 865-7, 1969.

⁶ Tepper JE, Noyes D, Krall JM, et al.: Intraoperative radiation therapy of pancreatic carcinoma: a report of RTOG-8505. Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 21 (5): 1145-9, 1991.

⁷ van den Bosch RP, van der Schelling GP, Klinkenbijl JH, et al.: Guidelines for the application of surgery and endoprostheses in the palliation of obstructive jaundice in advanced cancer of the pancreas. Ann Surg 219 (1): 18-24, 1994.

⁸ Polati E, Finco G, Gottin L, et al.: Prospective randomized double-blind trial of neurolytic coeliac plexus block in patients with pancreatic cancer. Br J Surg 85 (2): 199-201, 1998.

⁹ Kalser MH, Ellenberg SS: Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120 (8): 899-903, 1985.

¹⁰ Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer 59 (12): 2006-10, 1987.

¹¹ 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 cancer cooperative group. Ann Surg 230 (6): 776-82; discussion 782-4, 1999.

¹² Neoptolemos JP, Dunn JA, Stocken DD, et al.: Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 358 (9293): 1576-85, 2001.

¹³ Neoptolemos JP, Stocken DD, Friess H, et al.: A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350 (12): 1200-10, 2004.

¹⁴ Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.

¹⁵ Regine WF, Radiation Therapy Oncology Group: Phase III Randomized Study of Adjuvant Fluorouracil-Based Chemoradiotherapy Preceded and Followed By Fluorouracil Versus Gemcitabine in Patients With Resected Adenocarcinoma of the Pancreas, RTOG-9704, Clinical trial, Closed.

¹⁶ ESPAC-3(v2) Phase III Adjuvant Trial in Pancreatic Cancer Comparing 5FU and D-L-Folinic Acid vs. Gemcitabine. Leeds, UK: National Cancer Research Network Trials Portfolio, 2004. Available online. Last accessed May 5, 2006.

¹⁷ Rich TA, Radiation Therapy Oncology Group: Phase II Randomized Study of Gemcitabine, Paclitaxel, and Radiotherapy With or Without Tipifarnib in Patients With Locally Advanced Pancreatic Cancer, RTOG-PA-0020, Clinical trial, Closed.

¹⁸ Reni M, Panucci MG, Ferreri AJ, et al.: Effect on local control and survival of electron beam intraoperative irradiation for resectable pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys 50 (3): 651-8, 2001.

Stage IIB Pancreatic Cancer

Some patients with stage IIB pancreatic cancer have tumors that are technically resectable, but few cures have been reported, and these patients should be considered for clinical trials. Patients with unresectable tumors may also benefit from palliation of biliary obstruction by endoscopic, surgical, or radiological means.^1,

Although some data demonstrate a survival advantage associated with combined chemotherapy and radiation therapy,² most patients with unresectable pancreatic cancer should be considered for participation in clinical trials. Radiation therapy alone may palliate symptoms, but a survival benefit is not demonstrable.

Pain associated with unresectable pancreatic cancer may be palliated with radiation therapy, with or without chemotherapy,^2,3,4,5 or with chemical splanchnicectomy with 50% alcohol at the time of surgical exploration.⁶ Celiac nerve blocks and local neurosurgical procedures to relieve pain can be considered.^7,

Standard treatment options:

1. Pancreatectomy when feasible, with or without adjuvant fluorouracil (5-FU) chemotherapy and radiation therapy.^6,8,9,10,11,
2. Radiation therapy with 5-FU chemotherapy for patients with locally unresectable disease.^2,3,4,
3. Palliative surgical biliary and/or gastric bypass, percutaneous radiologic biliary stent placement, or endoscopic biliary stent placement.^12,13,

Treatment options under clinical evaluation:

1. For patients with resected tumors, postoperative radiation therapy with other chemotherapeutic agents. In 2002, the Radiation Therapy Oncology Group completed a prospective, multicenter randomized trial to evaluate whether gemcitabine chemotherapy administered prior to and following radiation with concurrent 5-FU is superior to adjuvant 5-FU for patients with completely resected tumors; preliminary analysis is pending.^14,
2. For patients with resected tumors, postoperative chemotherapy alone. The ESPAC-3 trial is ongoing to evaluate postoperative chemotherapy with either 5-FU/leucovorin or gemcitabine versus no additional treatment.¹⁵
3. For patients with technically unresectable tumors, biologic agents in combination with radiation and/or chemotherapy.^16,
4. For patients with locally unresectable tumors, preoperative radiation therapy with various chemotherapeutic agents and/or radiosensitizers is under clinical evaluation.
5. Intraoperative radiation therapy and/or implantation of radioactive sources.^5,17,

Information about ongoing clinical trials is available from the NCI Web site.

¹ Sohn TA, Lillemoe KD, Cameron JL, et al.: Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J Am Coll Surg 188 (6): 658-66; discussion 666-9, 1999.

² Moertel CG, Frytak S, Hahn RG, et al.: 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. Cancer 48 (8): 1705-10, 1981.

³ Whittington R, Solin L, Mohiuddin M, et al.: Multimodality therapy of localized unresectable pancreatic adenocarcinoma. Cancer 54 (9): 1991-8, 1984.

⁴ Moertel CG, Childs DS Jr, Reitemeier RJ, et al.: Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet 2 (7626): 865-7, 1969.

⁵ Tepper JE, Noyes D, Krall JM, et al.: Intraoperative radiation therapy of pancreatic carcinoma: a report of RTOG-8505. Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 21 (5): 1145-9, 1991.

⁶ Kalser MH, Ellenberg SS: Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120 (8): 899-903, 1985.

⁷ Polati E, Finco G, Gottin L, et al.: Prospective randomized double-blind trial of neurolytic coeliac plexus block in patients with pancreatic cancer. Br J Surg 85 (2): 199-201, 1998.

⁸ Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer 59 (12): 2006-10, 1987.

⁹ 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 cancer cooperative group. Ann Surg 230 (6): 776-82; discussion 782-4, 1999.

¹⁰ Neoptolemos JP, Dunn JA, Stocken DD, et al.: Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 358 (9293): 1576-85, 2001.

¹¹ Neoptolemos JP, Stocken DD, Friess H, et al.: A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350 (12): 1200-10, 2004.

¹² van den Bosch RP, van der Schelling GP, Klinkenbijl JH, et al.: Guidelines for the application of surgery and endoprostheses in the palliation of obstructive jaundice in advanced cancer of the pancreas. Ann Surg 219 (1): 18-24, 1994.

¹³ Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.

¹⁴ Regine WF, Radiation Therapy Oncology Group: Phase III Randomized Study of Adjuvant Fluorouracil-Based Chemoradiotherapy Preceded and Followed By Fluorouracil Versus Gemcitabine in Patients With Resected Adenocarcinoma of the Pancreas, RTOG-9704, Clinical trial, Closed.

¹⁵ ESPAC-3(v2) Phase III Adjuvant Trial in Pancreatic Cancer Comparing 5FU and D-L-Folinic Acid vs. Gemcitabine. Leeds, UK: National Cancer Research Network Trials Portfolio, 2004. Available online. Last accessed May 5, 2006.

¹⁶ Rich TA, Radiation Therapy Oncology Group: Phase II Randomized Study of Gemcitabine, Paclitaxel, and Radiotherapy With or Without Tipifarnib in Patients With Locally Advanced Pancreatic Cancer, RTOG-PA-0020, Clinical trial, Closed.

¹⁷ Reni M, Panucci MG, Ferreri AJ, et al.: Effect on local control and survival of electron beam intraoperative irradiation for resectable pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys 50 (3): 651-8, 2001.

Stage III Pancreatic Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Many patients with stage III pancreatic cancer have tumors that are technically unresectable because of local vessel impingement or invasion by tumor. These patients may benefit from palliation of biliary obstruction by endoscopic, surgical, or radiological means.^1,

Although some data demonstrate a survival advantage associated with combined chemotherapy and radiation therapy,² most patients with unresectable pancreatic cancer should be considered for participation in clinical trials. Radiation therapy alone may palliate symptoms, but a survival benefit is not demonstrable. Chemotherapy alone occasionally produces an objective antitumor response, but the limited survival warrants participation in clinical trials. Gemcitabine has shown durable disease palliation in patients with advanced or metastatic pancreatic cancer refractory to fluorouracil (5-FU).³ A phase III trial of gemcitabine versus 5-FU as first-line therapy in patients with advanced or metastatic adenocarcinoma of the pancreas reported a significant improvement in survival among patients treated with gemcitabine (1-year survival was 18% with gemcitabine as compared with 2% with 5-FU, P = .003).^4,[Level of evidence: 1iiA] A preliminary report, in abstract form, of a phase III trial in which 569 patients with advanced or metastatic pancreatic carcinomas showed that erlotinib (100 mg/day) modestly prolonged survival when combined with gemcitabine (1000 mg/m2 weekly) compared with gemcitabine alone.^5,6 Differences in overall survival favored the erlotinib arm (hazard ratio [HR] = 0.81; 95% confidence interval [CI], 0.67–0.97; P = .025). The corresponding median and 1-year survival rates for patients receiving erlotinib versus placebo were 6.4 months and 5.9 months, and 24% versus 17%, respectively.^5,[Level of evidence: 1iiA]

Pain associated with unresectable pancreatic cancer may be palliated with radiation therapy, with or without chemotherapy,^2,7,8,9 or with chemical splanchnicectomy with 50% alcohol at the time of surgical exploration.¹⁰ Celiac nerve blocks and local neurosurgical procedures to relieve pain can be considered.^11,

Standard treatment options:

1. Pancreatectomy when feasible, with or without adjuvant 5-FU chemotherapy and radiation therapy.^{10,12,13,14,15,}
2. Radiation therapy with 5-FU chemotherapy for patients with locally unresectable disease.^2,7,8,
3. Palliative surgical biliary and/or gastric bypass, percutaneous radiologic biliary stent placement, or endoscopic biliary stent placement.^16,17,

Treatment options under clinical evaluation:

1. For patients with resected tumors, postoperative radiation therapy with other chemotherapeutic agents. In 2002, the Radiation Therapy Oncology Group completed a prospective, multicenter randomized trial to evaluate whether gemcitabine chemotherapy administered prior to and following radiation with concurrent 5-FU is superior to adjuvant 5-FU for patients with completely resected tumors; preliminary analysis is pending.¹⁸
2. For patients with resected tumors, postoperative chemotherapy alone. The European Study for Pancreatic Cancer (ESPAC-3) trial is ongoing to evaluate postoperative chemotherapy with either 5-FU/leucovorin or gemcitabine versus no additional treatment.¹⁹
3. For patients with technically unresectable tumors, biologic agents in combination with radiation and/or chemotherapy.^20,
4. For patients with locally unresectable tumors, radiation combined with novel chemotherapeutic agents and/or radiosensitizers.^21, Gemcitabine is being explored in combination with radiation therapy.²²
5. Intraoperative radiation therapy and/or implantation of radioactive sources.^9,23,

Information about ongoing clinical trials is available from the NCI Web site.

¹ Sohn TA, Lillemoe KD, Cameron JL, et al.: Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J Am Coll Surg 188 (6): 658-66; discussion 666-9, 1999.

² Moertel CG, Frytak S, Hahn RG, et al.: 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. Cancer 48 (8): 1705-10, 1981.

³ Rothenberg ML, Moore MJ, Cripps MC, et al.: A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol 7 (4): 347-53, 1996.

⁴ Burris HA 3rd, Moore MJ, Andersen J, et al.: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15 (6): 2403-13, 1997.

⁵ Moore MJ, Goldstein D, Hamm J, et al.: Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group [NCIC-CTG]. [Abstract] J Clin Oncol 23 (Suppl 16): A-1, 1s, 2005.

⁶ Moore MJ, NCIC-Clinical Trials Group: Phase III Randomized Study of Gemcitabine With or Without Erlotinib in Patients With Unresectable Locally Advanced or Metastatic Pancreatic Cancer, CAN-NCIC-PA3, Clinical trial, Closed.

⁷ Whittington R, Solin L, Mohiuddin M, et al.: Multimodality therapy of localized unresectable pancreatic adenocarcinoma. Cancer 54 (9): 1991-8, 1984.

⁸ Moertel CG, Childs DS Jr, Reitemeier RJ, et al.: Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet 2 (7626): 865-7, 1969.

⁹ Tepper JE, Noyes D, Krall JM, et al.: Intraoperative radiation therapy of pancreatic carcinoma: a report of RTOG-8505. Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 21 (5): 1145-9, 1991.

¹⁰ Kalser MH, Ellenberg SS: Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120 (8): 899-903, 1985.

¹¹ Polati E, Finco G, Gottin L, et al.: Prospective randomized double-blind trial of neurolytic coeliac plexus block in patients with pancreatic cancer. Br J Surg 85 (2): 199-201, 1998.

¹² Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer 59 (12): 2006-10, 1987.

¹³ 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 cancer cooperative group. Ann Surg 230 (6): 776-82; discussion 782-4, 1999.

¹⁴ Neoptolemos JP, Dunn JA, Stocken DD, et al.: Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 358 (9293): 1576-85, 2001.

¹⁵ Neoptolemos JP, Stocken DD, Friess H, et al.: A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350 (12): 1200-10, 2004.

¹⁶ van den Bosch RP, van der Schelling GP, Klinkenbijl JH, et al.: Guidelines for the application of surgery and endoprostheses in the palliation of obstructive jaundice in advanced cancer of the pancreas. Ann Surg 219 (1): 18-24, 1994.

¹⁷ Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.

¹⁸ Regine WF, Radiation Therapy Oncology Group: Phase III Randomized Study of Adjuvant Fluorouracil-Based Chemoradiotherapy Preceded and Followed By Fluorouracil Versus Gemcitabine in Patients With Resected Adenocarcinoma of the Pancreas, RTOG-9704, Clinical trial, Closed.

¹⁹ ESPAC-3(v2) Phase III Adjuvant Trial in Pancreatic Cancer Comparing 5FU and D-L-Folinic Acid vs. Gemcitabine. Leeds, UK: National Cancer Research Network Trials Portfolio, 2004. Available online. Last accessed May 5, 2006.

²⁰ Rich TA, Radiation Therapy Oncology Group: Phase II Randomized Study of Gemcitabine, Paclitaxel, and Radiotherapy With or Without Tipifarnib in Patients With Locally Advanced Pancreatic Cancer, RTOG-PA-0020, Clinical trial, Closed.

²¹ Epelbaum R, Rosenblatt E, Nasrallah S, et al.: Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer. J Surg Oncol 81 (3): 138-43, 2002.

²² Li CP, Chao Y, Chi KH, et al.: Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: gemcitabine versus 5-fluorouracil, a randomized controlled study. Int J Radiat Oncol Biol Phys 57 (1): 98-104, 2003.

²³ Reni M, Panucci MG, Ferreri AJ, et al.: Effect on local control and survival of electron beam intraoperative irradiation for resectable pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys 50 (3): 651-8, 2001.

Stage IV Pancreatic Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

The low objective response rate and lack of survival benefit with current chemotherapy indicates clinical trials as appropriate treatment of all newly diagnosed patients. Occasional patients have palliation of symptoms when treated by chemotherapy with well-tested older drugs such as fluorouracil (5-FU). Gemcitabine has demonstrated activity in patients with pancreatic cancer and is a useful palliative agent.^1,2,3 A phase III trial of gemcitabine versus 5-FU as first-line therapy in patients with advanced or metastatic adenocarcinoma of the pancreas reported a significant improvement in survival among patients treated with gemcitabine (1-year survival was 18% with gemcitabine as compared with 2% with 5-FU, P = .003).^2,[Level of evidence: 1iiA] A preliminary report, in abstract form, of a phase III trial in which patients with advanced or metastatic pancreatic carcinomas showed that erlotinib (100 mg/day) modestly prolonged survival when combined with gemcitabine (1000 mg/m2 weekly) compared with gemcitabine alone.^4,5 Differences in overall survival (OS) favored the erlotinib arm (hazard ratio = 0.81; 95% confidence interval , 0.67–0.97; P = .025). The corresponding median and 1-year survival rates for patients receiving erlotinib versus placebo were 6.37 months and 5.91 months, and 24% versus 17%, respectively.^4,[Level of evidence: 1iiA] When 5-FU was added to gemcitabine and compared with gemcitabine alone, the median survival of patients with advanced or metastatic disease (6.7 months vs. 5.7 months, respectively, P = .09) was not significantly improved.^6,[Level of evidence: 1iiA] The addition of a farnesyl transferase inhibitor (R115777-tipifarnib) to gemcitabine did not prolong OS in patients with advanced pancreatic cancer as compared with single-agent gemcitabine.^7,[ Level of evidence: 1iA] A randomized, placebo-controlled trial demonstrated that chemical splanchnicectomy with 50% alcohol at the time of surgical exploration significantly reduces pain, particularly in those patients with preoperative pain.⁸

Standard treatment options:

1. Chemotherapy with gemcitabine or 5-FU.^{1,9,10,11,12,13,14,15,16,}
2. Pain-relieving procedures (e.g., celiac or intrapleural block) and supportive care.^17,
3. Palliative surgical biliary bypass, percutaneous radiologic biliary stent placement, or endoscopically placed biliary stents.^18,19,20,

Treatment options under clinical evaluation:

Clinical trials evaluating modulated 5-FU, new anticancer agents, or biologicals (phase I and phase II).^{9,10,11,12,13,14,16,21,22,23,24,25,26} Information about ongoing clinical trials is available from the NCI Web site.

¹ Rothenberg ML, Moore MJ, Cripps MC, et al.: A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol 7 (4): 347-53, 1996.

² Burris HA 3rd, Moore MJ, Andersen J, et al.: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15 (6): 2403-13, 1997.

³ Storniolo AM, Enas NH, Brown CA, et al.: An investigational new drug treatment program for patients with gemcitabine: results for over 3000 patients with pancreatic carcinoma. Cancer 85 (6): 1261-8, 1999.

⁴ Moore MJ, Goldstein D, Hamm J, et al.: Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group [NCIC-CTG]. [Abstract] J Clin Oncol 23 (Suppl 16): A-1, 1s, 2005.

⁵ Moore MJ, NCIC-Clinical Trials Group: Phase III Randomized Study of Gemcitabine With or Without Erlotinib in Patients With Unresectable Locally Advanced or Metastatic Pancreatic Cancer, CAN-NCIC-PA3, Clinical trial, Closed.

⁶ Berlin JD, Catalano P, Thomas JP, et al.: Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol 20 (15): 3270-5, 2002.

⁷ Van Cutsem E, van de Velde H, Karasek P, et al.: Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol 22 (8): 1430-8, 2004.

⁸ Lillemoe KD, Cameron JL, Kaufman HS, et al.: Chemical splanchnicectomy in patients with unresectable pancreatic cancer. A prospective randomized trial. Ann Surg 217 (5): 447-55; discussion 456-7, 1993.

⁹ MacDonald JS, Widerlite L, Schein PS: Biology, diagnosis, and chemotherapeutic management of pancreatic malignancy. Adv Pharmacol Chemother 14: 107-42, 1977.

¹⁰ Bukowski RM, Balcerzak SP, O'Bryan RM, et al.: Randomized trial of 5-fluorouracil and mitomycin C with or without streptozotocin for advanced pancreatic cancer. A Southwest Oncology Group study. Cancer 52 (9): 1577-82, 1983.

¹¹ DeCaprio JA, Mayer RJ, Gonin R, et al.: Fluorouracil and high-dose leucovorin in previously untreated patients with advanced adenocarcinoma of the pancreas: results of a phase II trial. J Clin Oncol 9 (12): 2128-33, 1991.

¹² Kelsen D, Hudis C, Niedzwiecki D, et al.: A phase III comparison trial of streptozotocin, mitomycin, and 5-fluorouracil with cisplatin, cytosine arabinoside, and caffeine in patients with advanced pancreatic carcinoma. Cancer 68 (5): 965-9, 1991.

¹³ O'Connell MJ: Current status of chemotherapy for advanced pancreatic and gastric cancer. J Clin Oncol 3 (7): 1032-9, 1985.

¹⁴ Crown J, Casper ES, Botet J, et al.: Lack of efficacy of high-dose leucovorin and fluorouracil in patients with advanced pancreatic adenocarcinoma. J Clin Oncol 9 (9): 1682-6, 1991.

¹⁵ Carmichael J, Fink U, Russell RC, et al.: Phase II study of gemcitabine in patients with advanced pancreatic cancer. Br J Cancer 73 (1): 101-5, 1996.

¹⁶ Haller DG: Chemotherapy for advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 56 (4 Suppl): 16-23, 2003.

¹⁷ Polati E, Finco G, Gottin L, et al.: Prospective randomized double-blind trial of neurolytic coeliac plexus block in patients with pancreatic cancer. Br J Surg 85 (2): 199-201, 1998.

¹⁸ van den Bosch RP, van der Schelling GP, Klinkenbijl JH, et al.: Guidelines for the application of surgery and endoprostheses in the palliation of obstructive jaundice in advanced cancer of the pancreas. Ann Surg 219 (1): 18-24, 1994.

¹⁹ Sohn TA, Lillemoe KD, Cameron JL, et al.: Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J Am Coll Surg 188 (6): 658-66; discussion 666-9, 1999.

²⁰ Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.

²¹ Rougier P, Adenis A, Ducreux M, et al.: A phase II study: docetaxel as first-line chemotherapy for advanced pancreatic adenocarcinoma. Eur J Cancer 36 (8): 1016-25, 2000.

²² Bramhall SR, Rosemurgy A, Brown PD, et al.: Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial. J Clin Oncol 19 (15): 3447-55, 2001.

²³ Stathopoulos GP, Mavroudis D, Tsavaris N, et al.: Treatment of pancreatic cancer with a combination of docetaxel, gemcitabine and granulocyte colony-stimulating factor: a phase II study of the Greek Cooperative Group for Pancreatic Cancer. Ann Oncol 12 (1): 101-3, 2001.

²⁴ Feliu J, López Alvarez MP, Jaraiz MA, et al.: Phase II trial of gemcitabine and UFT modulated by leucovorin in patients with advanced pancreatic carcinoma. The ONCOPAZ Cooperative Group. Cancer 89 (8): 1706-13, 2000.

²⁵ Rocha Lima CM, Savarese D, Bruckner H, et al.: Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer. J Clin Oncol 20 (5): 1182-91, 2002.

²⁶ Smith D, Gallagher N: A phase II/III study comparing intravenous ZD9331 with gemcitabine in patients with pancreatic cancer. Eur J Cancer 39 (10): 1377-83, 2003.

Recurrent Pancreatic Cancer

Chemotherapy occasionally produces objective antitumor response, but the low percentage of significant responses and lack of survival advantage warrant use of therapies under evaluation.^1,

Standard treatment options:

1. Chemotherapy (fluorouracil ² or gemcitabine ^3,4,5,).
2. Palliative surgical bypass procedures, endoscopic or radiologically placed stents.^6,7,
3. Palliative radiation procedures.
4. Pain relief by celiac axis nerve or intrapleural block (percutaneous).^8,
5. Other palliative medical care alone.

Treatment options under clinical evaluation:

Clinical trials evaluating pharmacologic modulation of fluorinated pyrimidines, new anticancer agents, or biologicals (phase I and II). Information about ongoing clinical trials is available from the NCI Web site.

¹ Yeo CJ, Yeo TP, Hruban RH: Cancer of the pancreas. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 945-82.

² Cullinan SA, Moertel CG, Fleming TR, et al.: A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA 253 (14): 2061-7, 1985.

³ Rothenberg ML, Moore MJ, Cripps MC, et al.: A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol 7 (4): 347-53, 1996.

⁴ Burris HA 3rd, Moore MJ, Andersen J, et al.: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15 (6): 2403-13, 1997.

⁵ Storniolo AM, Enas NH, Brown CA, et al.: An investigational new drug treatment program for patients with gemcitabine: results for over 3000 patients with pancreatic carcinoma. Cancer 85 (6): 1261-8, 1999.

⁶ Sohn TA, Lillemoe KD, Cameron JL, et al.: Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J Am Coll Surg 188 (6): 658-66; discussion 666-9, 1999.

⁷ Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.

⁸ Polati E, Finco G, Gottin L, et al.: Prospective randomized double-blind trial of neurolytic coeliac plexus block in patients with pancreatic cancer. Br J Surg 85 (2): 199-201, 1998.

Changes to This Summary (3/15/2007)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information

Updated statistics with estimated new cases and deaths for 2007 (cited American Cancer Society as reference 1).

More Information

About PDQ

• PDQ® - NCI's Comprehensive Cancer Database.
  • Full description of the NCI PDQ database.

Additional PDQ Summaries

• PDQ® Cancer Information Summaries: Adult Treatment
  • Treatment options for adult cancers.
• PDQ® Cancer Information Summaries: Pediatric Treatment
  • Treatment options for childhood cancers.
• PDQ® Cancer Information Summaries: Supportive Care
  • Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.
• PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer)
  • Tests or procedures that detect specific types of cancer.
• PDQ® Cancer Information Summaries: Prevention
  • Risk factors and methods to increase chances of preventing specific types of cancer.
• PDQ® Cancer Information Summaries: Genetics
  • Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.
• PDQ® Cancer Information Summaries: Complementary and Alternative Medicine
  • Information about complementary and alternative forms of treatment for patients with cancer.

Important:

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