Chemotherapy, Interferon Alfa, and Radiation Therapy in Treating Patients Who Have Undergone Surgery For Pancreatic Cancer

OBJECTIVES:

Primary

* Determine the overall survival of patients with previously resected pancreatic adenocarcinoma treated with postoperative cisplatin, interferon alfa, fluorouracil, and concurrent radiotherapy.
* Determine the toxic effects of this regimen in these patients.

Secondary

* Determine the disease-specific, biochemical failure-free, and symptom/treatment-free survival of patients treated with this regimen.
* Determine the quality of life of patients treated with this regimen.

OUTLINE:

* Chemoradiotherapy: Patients receive fluorouracil intravenous (IV) continuously and interferon alfa subcutaneously (SQ) 3 times per week (total of 17 doses) on days 1-19 and 29-45 and cisplatin IV over 6 hours on days 1, 8, 15, 29, 36 and 43. Patients also undergo concurrent radiotherapy once daily, 5 days a week in weeks 1-3 and 5-7 (28 fractions).
* Post-chemoradiotherapy fluorouracil: Patients receive fluorouracil IV continuously on days 71-108 and 127-168.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

• Recombinant Interferon Alfa (Biological), also known as Interferon alfa-2b, IFN: 3 million units subcutaneously every other day (Monday, Wednesday and Friday) during Days 1-19 and 29-45, for 6 1/2 weeks totaling 17 doses.
• Cisplatin (Drug), also known as Platinol-AQ, Platinol, CDDP: 30 mg/m\^2 IV over 60 minutes on days 1, 8, 15, 29, 36, 43 - weekly for total 6 doses, during 5 1/2 weeks radiation therapy.
• Fluorouracil (Drug), also known as 5-fluorouracil, Adrucil, Efudex: 175 mg/m\^2/day continuous infusion over 6 1/2 weeks for total 3 courses: Days 1-19 and 29-45, Days 71-108 and Days 127-168.
• Radiation Therapy (Radiation), also known as RT, Radiatherapy: External beam radiation on days 1-19 and days 29-45, 9 day treatment break on day 20.

Primary outcomes

• Median Overall Survival (OS) [Participants followed till disease progression or death (approximately 6 years)]: Overall Survival defined overall survival time, measured from date of tissue diagnosis till disease progression or death.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Biopsy proven completely resected (R0 or R1) pancreatic adenocarcinoma of the pancreatic head or uncinate process \[American Joint Committee on Cancer (AJCC) Stage I-III\]. Surgery (pancreaticoduodenectomy) may be performed at M. D. Anderson Cancer Center or prior to referral to M. D. Anderson Cancer Center. Protocol treatment must begin within 12 weeks of surgery.
2. Postoperative (pre-treatment) computed tomography (CT) scan without evidence of radiographically defineable residual primary/metastatic disease or clinically significant post-surgical changes.
3. Staging studies completed within three weeks +/- 3 days of protocol registration.
4. Hemoglobin (Hb) >9.0 g/%, White Blood Count (WBC) >3,000 cells/mm3 (Absolute neutrophil count (ANC)>1,500 cells/mm3), platelets >75,000 cells/mm3.
5. Postoperative serum calcium (CA) 19-9 < 100.
6. Performance status: Zubrod 0 or 1.
7. Creatinine £1.5 mg/dL and calculated or measured creatinine clearance (CrCl) of 60 ml/min or greater by the following formula: Creatinine clearance rate (CrCl) = (140 - age) * Weight (kg) * 0.85 (female) OR * 1.00 (male) 72 * serum creatinine
8. Patients should have bilateral renal function, as determined on excretory urogram (IVP) or abdominal CT, or ³ 2/3 of one functioning kidney must be able to be shielded from the radiation beam.
9. No acute infections at the time of therapy initiation.
10. Women of childbearing potential must agree to practice adequate contraception and to refrain from breast feeding, as specified in the informed consent.
11. Patients must sign a study-specific consent form, which is attached to this protocol.
12. Patients with a prior history of non-pancreatic malignancy who are free of disease from their primary cancer may be eligible at the discretion of the study chair.

Exclusion Criteria:

1. Residual (clinical or CT definable) metastatic or incompletely resected local disease.
2. Patients with positive peritoneal cytology (for adenocarcinoma) detected at laparotomy for pancreaticoduodenectomy or as part of prior laparoscopic assessment of peritoneal cytology.
3. Patients with a history of hypersensitivity to interferon alfa-2b.
4. Patients with significant cardiovascular disease, such as unstable angina or congestive heart failure.
5. Pregnancy or breastfeeding.
6. Patients with severe pulmonary disease.
7. Children under the age of 18 are excluded (as the disease is rare and toxicity profile of this regimen untested in pediatric patients).
8. Presence or history of severe depression.

Participant flow

Outcome results

• Median Overall Survival (OS) (Primary), Median, months: Postoperative Chemoradiation Regimen 42 (32.1 to 64.5)

Adverse events

Time frame: Toxicity assessed for participants while on 6 week chemoradiation treatment period with a one week break (equivalent 7 weeks). Data collected over 7 years and 4 months through on-going follow up.

Serious adverse events by term

• Peter W. Pisters, MD, Study chair, M.D. Anderson Cancer Center

NIH grants: P30CA016672