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Pancreatic Cancer (PDQ®): Treatment
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Table of Contents

General Information
Cellular Classification
Stage Information
TNM definitions
AJCC stage groupings
Treatment Option Overview
Stage I Pancreatic Cancer
Stage IIA Pancreatic Cancer
Stage IIB Pancreatic Cancer
Stage III Pancreatic Cancer
Stage IV Pancreatic Cancer
Recurrent Pancreatic Cancer
Changes to This Summary (06/22/2004)
More Information

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 2004:[1]

  • New cases: 31,860.
  • Deaths: 31,270.

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 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 rate of less than 4%.[3] The highest cure rate occurs if the tumor is truly localized to the pancreas; however, this stage of 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 overall survival rate of all stages is less than 1% at 5 years with most patients dying within 1 year.[7-10]

There are no tumor-specific markers 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] However, the presence of a normal CA 19-9 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. However, palliation of symptoms may be achieved with conventional treatment. Symptoms due to 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 overall survival.[12,13] Palliative efforts may also be directed to the potentially disabling psychological events associated with the diagnosis and treatment of pancreatic cancer.[14]

References

  1. American Cancer Society.: Cancer Facts and Figures 2004. Atlanta, Ga: American Cancer Society, 2004. Also available online. Last accessed May 13, 2004. 

  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.  [PUBMED Abstract]

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

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

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

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

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

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

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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 (this tumor has lower malignant potential, and may be cured with surgery alone).[1,2]

Borderline Malignancies

  • Mucinous cystic tumor with dysplasia.
  • Intraductal papillary mucinous tumor with dysplasia.[3]
  • Pseudopapillary solid tumor.

References

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

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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. However, in order to communicate a uniform definition of disease, 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 limited to the pancreas, 2 cm or less in greatest dimension
  • T2: Tumor limited to the pancreas, 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

References

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

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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.[3-5] [Level of evidence: 3iA] Frequently, malabsorption due to 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.

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

References

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

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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%.[1-5] 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 due to the high incidence of both local and distant tumor recurrence.[6-8] [Level of evidence: 3iA] The role of postoperative therapy in the management of this disease is inadequately defined as there are limited randomized clinical trial data to support the use of postoperative therapy in patients with resected pancreatic cancer.[9-13] These trials are all 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 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 toward improved median, 2-year, and 5-year overall survival with adjuvant therapy compared with surgery alone (12.6 months, 23%, 10% vs 17.1 months, 37% and 20%, 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 1 of 4 groups (i.e., observation, chemotherapy, chemoradiation or chemoradiation followed by additional chemotherapy), with a 2 X 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 there was a high rate of protocol nonadherence.[12-14] [Level of evidence: 1iiA] Additional trials are still warranted, therefore, 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 chemoradiation (CRT), CRT with protracted infusion 5-FU or the addition of mitomycin-C, CRT with elective hepatic irradiation, 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.[15-19]

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 irradiation.[9-13]

Treatment options under clinical evaluation:

  1. 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 Cancer.gov Web site.
  2. Postoperative chemotherapy alone. The ESPAC-3 trial is ongoing to evaluate postoperative chemotherapy with either 5-FU/leucovorin or gemcitabine versus no additional treatment.[23]
  3. Postoperative biologic agents including farnesyl transferase inhibitors and avastin in combination with radiation therapy and/or chemotherapy.

References

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

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

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

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

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

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

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PDQ Clinical Trial]

  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 June 7, 2004. 

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Stage IIA Pancreatic Cancer

Some patients with stage IIA pancreatic cancer have tumors that are technically unresectable; these patients may benefit from palliative bypass of biliary obstruction by surgical, endoscopic, or radiologic means.[1] While there are some data demonstrating a survival advantage associated with combined chemotherapy and radiation therapy for patients with locally advanced unresectable disease,[2-4] 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,[2-5] 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.[8-12]
  2. Radiation therapy with 5-FU chemotherapy for patients with locally unresectable disease.[2-4]
  3. Palliative surgical biliary bypass, percutaneous radiologic biliary stent placement, or endoscopic biliary stent placement.[6,13]

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. 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. Postoperative biologic agents including farnesyl transferase inhibitors and avastin in combination with radiation and/or chemotherapy.
  4. For patients with locally unresectable tumors, preoperative irradiation 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.[5,16]

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

References

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

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

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  6. 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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

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

  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.  [PUBMED Abstract]

  10. 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.  [PUBMED Abstract]

  11. 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.  [PUBMED Abstract]

  12. 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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PDQ Clinical Trial]

  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 June 7, 2004. 

  16. 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.  [PUBMED Abstract]

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Stage IIB Pancreatic Cancer

A few patients with stage IIB pancreatic cancer have tumors that are technically resectable, but few cures have been reported. More frequently, palliative bypass of biliary obstruction by surgical, endoscopic, or radiologic means should be performed.[1]

While there are data demonstrating 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,[2-5] 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.[6,8-11]
  2. Radiation therapy with 5-FU chemotherapy for patients with locally unresectable disease.[2-4]
  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. 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. Postoperative biologic agents including farnesyl transferase inhibitors and avastin in combination with radiation and/or chemotherapy.
  4. For patients with locally unresectable tumors, preoperative irradiation with various chemotherapeutic agents and/or radiosensitizers is under clinical evaluation.
  5. Intraoperative radiation therapy and/or implantation of radioactive sources.[5,16]

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

References

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

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

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

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

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PDQ Clinical Trial]

  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 June 7, 2004. 

  16. 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.  [PUBMED Abstract]

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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, due to local vessel impingement or invasion by tumor. Therefore, palliative bypass of biliary obstruction by surgical, endoscopic, or radiologic means may be performed.[1]

While there are data demonstrating 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 to 2% with 5-FU, P=.003).[4] [Level of evidence: 1iiA]

Pain associated with unresectable pancreatic cancer may be palliated with radiation therapy, with or without chemotherapy,[2,5-7] or with chemical splanchnicectomy with 50% alcohol at the time of surgical exploration.[8] Celiac nerve blocks and local neurosurgical procedures to relieve pain can be considered.[9]

Standard treatment options:

  1. Pancreatectomy when feasible, with or without adjuvant 5-FU chemotherapy and radiation therapy.[8,10-13]
  2. Radiation therapy with 5-FU chemotherapy for patients with locally unresectable disease.[2,5,6]
  3. Palliative surgical biliary and/or gastric bypass, percutaneous radiologic biliary stent placement, or endoscopic biliary stent placement.[14,15]

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.[16]
  2. Postoperative chemotherapy alone. The ESPAC-3 trial is ongoing to evaluate postoperative chemotherapy with either 5-FU/leucovorin or gemcitabine versus no additional treatment.[17]
  3. Postoperative biologic agents including farnesyl transferase inhibitors and avastin in combination with radiation and/or chemotherapy.
  4. For patients with locally unresectable tumors, radiation combined with novel chemotherapeutic agents and/or radiosensitizers.[18] Gemcitabine is being explored in combination with radiation therapy.[19]
  5. Intraoperative radiation therapy and/or implantation of radioactive sources.[7,20]

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

References

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

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

  6. 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.  [PUBMED Abstract]

  7. 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.  [PUBMED Abstract]

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

  9. 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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  14. 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.  [PUBMED Abstract]

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

  16. 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.  [PDQ Clinical Trial]

  17. 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 June 7, 2004. 

  18. 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.  [PUBMED Abstract]

  19. 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.  [PUBMED Abstract]

  20. 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.  [PUBMED Abstract]

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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.[1-3] 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 to 2% with 5-FU, P=.003).[2] [Level of evidence: 1iiA] When 5-FU was added to gemcitabine and compared to 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.[4] [Level of evidence: 1iiA] 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.[5]

Standard treatment options:

  1. Chemotherapy with gemcitabine or fluorouracil.[1,6-13]
  2. Pain-relieving procedures (e.g., celiac or intrapleural block) and supportive care.[14]
  3. Palliative surgical biliary bypass, percutaneous radiologic biliary stent placement, or endoscopically placed biliary stents.[15-17]

Treatment options under clinical evaluation:

Clinical trials evaluating modulated fluorouracil, new anticancer agents, or biologicals (phase I and II).[6-11,13,18-23] Information about ongoing clinical trials is available from the NCI Cancer.gov Web site.

References

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  4. 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.  [PUBMED Abstract]

  5. 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.  [PUBMED Abstract]

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

  7. 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.  [PUBMED Abstract]

  8. 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.  [PUBMED Abstract]

  9. 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.  [PUBMED Abstract]

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

  11. 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.  [PUBMED Abstract]

  12. 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.  [PUBMED Abstract]

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

  14. 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.  [PUBMED Abstract]

  15. 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.  [PUBMED Abstract]

  16. 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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  18. 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.  [PUBMED Abstract]

  19. 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.  [PUBMED Abstract]

  20. 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.  [PUBMED Abstract]

  21. 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.  [PUBMED Abstract]

  22. 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.  [PUBMED Abstract]

  23. 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.  [PUBMED Abstract]

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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 [3-5] ).
  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 Cancer.gov Web site.

References

  1. Evans DB, Abbruzzese JL, Willett CG: Cancer of the pancreas. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2001, pp 1126-1161. 

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

  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.  [PUBMED Abstract]

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Changes to This Summary (06/22/2004)

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

Added estimated new cases and deaths from pancreatic cancer in the US in 2004 (cited American Cancer Society).

Stage I Pancreatic Cancer

Added text to state that the role of postoperative therapy in the management of this disease is inadequately defined. Added 2004 Neoptolemos et al. and Choti as references 13 and 14, respectively. Added text to state that an analysis of the ESPAC 1 trial that examined only patients who underwent strict randomization following pancreatic resection to 1 of 4 groups (i.e., observation, chemotherapy, chemoradiation or chemoradiation followed by additional chemotherapy), with a 2 X 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 there was a high rate of protocol nonadherence. Additional trials are still warranted, therefore, to determine effective adjuvant therapy for this disease.

Added postoperative chemotherapy alone (cited ESPAC trial) and biologic agents as new treatment options under clinical evaluation.

Stage IIA Pancreatic Cancer

Added postoperative chemotherapy alone (cited ESPAC trial) and postoperative biologic agents as treatment options under clinical evaluation. Added Klinkenbijl et al., 2001 Neoptolemos et al., and 2004 Neoptolemos et al. as references 10, 11, and 12, respectively.

Stage III Pancreatic Cancer

Added postoperative chemotherapy alone (cited ESPAC trial) and postoperative biologic agents as treatment options under clinical evaluation. Added Klinkenbijl et al., 2001 Neoptolemos et al., and 2004 Neoptolemos et al. as references 11, 12, and 13, respectively.

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Important:

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

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