Interferon Boosts Survival After Pancreatic Cancer Resection

Carole Bullock

March 10, 2011

March 10, 2011 (San Antonio, Texas) — Adjuvant interferon was tolerated and improved survival in a small study of patients undergoing pancreaticoduodenectomy, researchers reported here at the Society of Surgical Oncology 64th Annual Cancer Symposium.

Matthew Katz, MD, assistant professor of surgery, University of Texas M.D. Anderson Cancer Center, Houston, noted that most patients experienced some adverse effects, but "all were grade 3 events, and the most common were hematologic."

In several major trials, adjuvant interferon has shown an overall survival benefit, but patients need to be advised about the possibility of adverse effects, researchers note.

"There has been interest in the use of interferon-based chemoradiation as adjuvant therapy for patients with pancreatic cancer for more than 10 years, but there have been concerns about its toxicity. We hypothesized that we could administer this regimen safely, with minimal adverse effects on patients' quality of life," Dr. Katz said in an interview with Medscape Medical News.

"For well-selected patients, there is significant benefit and most of the side effects are reversible. The study shows there is a favorable overall outcome," he said.

In the single-center phase 2 study, toxicity, quality of life, and survival were determined in 29 patients with resected pancreatic head adenocarcinoma who received 1 of 3 protocols: interferon-alfa-2b (3 million units on Monday, Wednesday, and Friday), cisplatin (30 mg/m2, 6 doses), and 5-fluorouracil (175 mg/m2 per day).

All patients had T3 tumors, 22 (79%) had positive lymph nodes, and 4 (14%) had positive (R1) margins. In all, 24 patients (86%) completed therapy.

After 62 months, 19 patients had died and 20 had recurrences (6 local, 13 distant, and 1 combined).

The median duration of overall survival for treated patients was 42.3 months (95% confidence interval, 30.5 to 54.2 months); 86% completed therapy.

Adverse effects included leukopenia (15 patients [54%]), neutropenia (12 patients [43%]), and fatigue, anorexia, and stomatitis (8 patients each [29%]). No grade 4 toxicity occurred.

According to Dr. Katz, "although the study was limited by its small size and unrandomized design, the overall survival duration of 42 months was remarkable, and almost twice . . . that typically associated with standard chemotherapy and chemoradiation regimens."

Patients were treated with external-beam radiation (50.4 Gy) followed by 2 courses of systemic 5-fluorouracil. The protocol was modified after the eleventh patient to include a 1-week break in the middle of chemoradiation.

Eastern Cooperative Oncology Group Performance Status ranged from 0 (11 patients [39%]) to 1 (17 patients [61%]). Quality of life was assessed using validated instruments based on a point system evaluating how well the patient felt after treatment.

Researchers concluded that interferon-based chemoradiation is associated with favorable survival when administered to patients with good performance status in the adjuvant setting at experienced treatment centers.

According to Charles Scoggins, MD, MBA, associate professor of surgical oncology at the University of Louisville, Kentucky, who moderated the session, "these data show a vast improvement in overall survival for patients afflicted with pancreatic cancer. This single-center report mirrors [the results] shown by the [group from the] Virginia Mason [Medical Center, in Seattle, Washington], and adds further evidence that under tightly controlled circumstances, the addition of interferon to adjuvant chemoradiation can provide real benefit to the patient while managing the challenging and complex toxicity profile.

"Unfortunately, this toxicity profile proved too much for the randomized multicenter trial that was conducted by the American College of Surgeons Oncology Group, leading to early stoppage of the trial."

"Further data are needed to confirm the wonderful results presented by Dr. Katz," Dr. Scoggins added.

Asked by Medscape Medical News to comment on the study, Clifford Cho, MD, FACS, assistant professor, Department of Surgery, University of Wisconsin School of Medicine and Public Health in Madison, said: "This nice study illuminates 3 points regarding a chemotherapeutic regimen that has demonstrated great therapeutic potential but almost insurmountable toxicity."

"First, the early survival outcomes are promising and seem to corroborate the potential for survival benefit observed in the original Virginia Mason trial."

"Second, although significant treatment-related morbidity was again seen, protocol measures instituted to anticipate and treat these toxicities allowed the investigators to pull these patients through to completion."

"Finally, it appears that the impact of these toxicities on participants' quality of life might not be as negative as one might have expected — raising the interesting possibility that patients may be more willing to endure treatment-related toxicity than we thought."

"Ultimately, I think this study might reinvigorate investigative interest in this regimen for healthy, carefully selected people with pancreatic adenocarcinoma," Dr. Cho concluded.

The study was supported by University of Texas M.D. Anderson Cancer Center, Houston. The author has disclosed no relevant financial relationships.

Society of Surgical Oncology (SSO) 64th Annual Cancer Symposium: Abstract31. Presented March 4, 2011.


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