Adjuvant Chemoradiotherapy and Interferon Alfa in Treating Patients With Resected Pancreatic Cancer

• Toxicity [ Designated as safety issue: Yes ]
• Disease-free survival [ Designated as safety issue: No ]
• Local-regional disease control [ Designated as safety issue: No ]
• Distant disease control [ Designated as safety issue: No ]

RATIONALE: Drugs used in chemotherapy, such as fluorouracil and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Interferon alfa may interfere with the growth of tumor cells. Radiation therapy uses high-energy radiation from x-rays and other sources to kill tumor cells. Combining chemotherapy with interferon alfa and giving them with radiation therapy after surgery may kill any remaining tumor cells.

PURPOSE: Phase II trial to study the effectiveness of adjuvant chemoradiotherapy and interferon alfa in treating patients who have resected stage I, stage II, or stage III pancreatic cancer.

OBJECTIVES:

• Determine the disease-free and overall survival of patients with resected pancreatic adenocarcinoma treated with adjuvant chemoradiotherapy comprising fluorouracil, cisplatin, and interferon alfa.
• Determine the rate and severity of acute and late toxic effects in patients treated with this regimen.
• Determine the local-regional disease control and distant disease control in patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Chemoradiotherapy (CRT): Patients receive fluorouracil IV continuously on days 1-38; cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36; and interferon alfa subcutaneously on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, 33, 36, and 38. Patients also undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38.
• Post-CRT chemotherapy: Beginning 4-6 weeks after the completion of CRT, patients receive fluorouracil IV continuously on days 1-42. Treatment repeats every 56 days for a total of two courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 93 patients will be accrued for this study within 2 years.

• Biological: recombinant interferon alfa
• Drug: cisplatin
• Drug: fluorouracil
• Procedure: adjuvant therapy
• Radiation: radiation therapy

• Picozzi VJ, Abrams RA, Decker PA, Traverso W, O'Reilly EM, Greeno E, Martin RC, Wilfong LS, Rothenberg ML, Posner MC, Pisters PW; for the American College of Surgeons Oncology Group. Multicenter phase II trial of adjuvant therapy for resected pancreatic cancer using cisplatin, 5-fluorouracil, and interferon-alfa-2b-based chemoradiation: ACOSOG Trial Z05031. Ann Oncol. 2010 Jul 29; [Epub ahead of print]
• Picozzi VJ, Abrams RA, Traverso LW, et al.: ACOSOG Z05031: initial report of a multicenter, phase II trial of a novel chemoradiation protocol using cisplatin, 5-FU, and alpha- interferon as adjuvant therapy for resected pancreas cancer. [Abstract] American Society of Clinical Oncology 2008 Gastrointestinal Cancers Symposium, 25-27 January 2008, Orlando, FL. A-125, 2008.
• Picozzi VJ, Abrams RA, Traverso LW, et al.: ACOSOG Z05031: report on a multicenter, phase II trial for adjuvant therapy of resected pancreatic cancer using cisplatin, 5- FU, and alpha-interferon. [Abstract] J Clin Oncol 26 (Suppl 15): A-4505, 2008.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the head of the pancreas

  • Stage I, II, or III (T1-4, N0-1, M0)
  • No recurrent pancreatic cancer

• Must have undergone a potentially curative gross total resection by pancreaticoduodenectomy within the past 56 days

  • Must have R0 (no residual tumor) or R1 (microscopic residual tumor) grade disease post-resection

• No pancreaticoduodenectomy histopathology indicating any of the following types:

  • Adenosquamous carcinoma
  • Ampullary carcinoma
  • Carcinoid tumor
  • Cystadenocarcinoma
  • Cystadenoma
  • Distal common bile duct carcinoma
  • Duodenal carcinoma
  • Islet cell carcinoma
• No metastatic disease by CT scan of the chest and CT scan with intravenous contrast (or MRI) of abdomen/pelvis

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1 OR
• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin greater than 9.5 g/dL

Hepatic

• Bilirubin no greater than 3 mg/dL
• AST and ALT no greater than 2 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Stable or increasing weight within 14 days before start of study treatment (otherwise supplemental nutrition, such as feeding jejunostomy, percutaneous endoscopic gastrostomy, or total parenteral nutrition, must be initiated)
• No evidence of recurrence of any prior malignancy
• No other malignancies within the past 5 years except successfully treated carcinoma in situ of the cervix, lobular carcinoma in situ of the breast, or nonmelanoma skin cancer
• No preexisting psychiatric condition (especially depression) or a history of severe psychiatric disorders

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biologic or immunologic therapies
• No concurrent biological response modifiers for pancreatic cancer
• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
• No concurrent oprelvekin

Chemotherapy

• No prior systemic chemotherapy for pancreatic cancer

Endocrine therapy

• No concurrent dexamethasone

Radiotherapy

• No prior radiotherapy for pancreatic cancer
• No prior external beam photon (x-ray) therapy to the chest, abdomen, or pelvis
• No concurrent intensity modulated radiotherapy

Surgery

• See Disease Characteristics

Other

• Underwent potentially curative therapy for any prior malignancies
• No prior chronic immunosuppressive therapy (e.g., prednisone or methotrexate) for collagen vascular disease or other chronic immunologic abnormality
• No concurrent theophylline
• No concurrent aminoglycoside antibiotics
• No concurrent halogenated antiviral agents (e.g., sorivudine)
• No other concurrent investigational drugs for pancreatic cancer
• No other concurrent systemic or loco-regional therapy for pancreatic cancer