• Gastrointestinal Cancer Disease Site Group. Earle CC, Agboola O, Maroun J, Zuraw L. The treatment of locally advanced pancreatic cancer [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2004 Feb 20 [online update]. 17 p. (Practice guideline report; no. 2-7). [29 references]

Locally advanced (unresectable but non-metastatic) pancreatic cancer

Assessment of Therapeutic Effectiveness
Evaluation
Treatment

Oncology
Radiation Oncology

Physicians

To evaluate the optimal treatment for patients with locally advanced (unresectable but non-metastatic) pancreatic cancer

Adult patients with locally advanced (unresectable but nonmetastatic) adenocarcinoma of the exocrine pancreas

1. Chemoradiotherapy (bolus 5-fluorouracil [5-FU] combined with radiation)
2. Radiotherapy alone
3. Chemotherapy alone
4. Anti-cancer treatments (listed above) in combination with supportive care (e.g., pain control, nutritional support)

Note: Guideline developers considered but did not recommend supportive care alone in patients medically suitable for chemotherapy and radiation treatment.

• Overall survival
• Disease-free survival
• Local control
• Adverse effects
• Quality of life

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases

22 randomized trials, one abstract report of a meta-analysis, and one preliminary repot of an ongoing trial were reviewed.

Expert Consensus (Committee)

Not applicable

Review of Published Meta-Analyses
Systematic Review with Evidence Tables

Quantitative meta-analysis was not undertaken because the trials were too clinically heterogeneous to pool. The doses of radiotherapy varied widely, as did the chemotherapeutic agents and schedules.

Expert Consensus

The Gastrointestinal Cancer Disease Site Group (DSG) reached fairly easy consensus on the guideline recommendations. Since the evidence for radiation is relatively weak, there was discussion around whether treatment with gemcitabine alone should be presented as an equally acceptable alternative. The only randomized data on gemcitabine is the study by Burris et al, which demonstrated that gemcitabine improves symptoms and modestly improves survival compared with 5-fluorouracil (FU) as single-agent chemotherapy in patients with locally advanced or metastatic pancreatic cancer. These patients were symptomatic, had a life expectancy of at least twelve weeks, and had a Karnofsky performance status of at least 50% (equivalent to an Eastern Cooperative Oncology Group [ECOG] performance status of less than 3). This randomized trial is discussed in detail in another guideline developed by the Gastrointestinal Cancer DSG, which concludes that gemcitabine is a reasonable treatment option in patients with locally advanced or metastatic pancreatic cancer. Since 26% of the patients included in the randomized trial by Burris et al had locally advanced disease (although they were not reported separately) and since the overall results detected a benefit with gemcitabine, the Gastrointestinal Cancer DSG inferred that patients with locally advanced disease unable to undergo radiation may be appropriately treated as having metastatic disease. A qualifying statement noting this was added to the recommendations.

The majority of Gastrointestinal Cancer DSG members felt that changing the phrase that states combined chemoradiotherapy is the "recommended standard" to "current conventional practice" was appropriate. Also, a qualifying statement that indicates to the reader that the evidence on which current conventional practice is based is modest at best was added to the recommendations. Based on feedback from the DSG members, some suggested chemotherapy regimens were added to the text of the document.

Not applicable

A formal cost analysis was not performed and published cost analyses were not reviewed.

External Peer Review
Internal Peer Review

Practitioner feedback was obtained through a mailed survey of 152 practitioners in Ontario (29 medical oncologists, 20 radiation oncologists, and 103 surgeons). The survey consisted of items evaluating the methods, results, and interpretive summary used to inform the draft recommendations and whether the draft recommendations above should be approved as a practice guideline. Written comments were invited. Follow-up reminders were sent at two weeks (post card) and four weeks (complete package mailed again). The Gastrointestinal Cancer Disease Site Group (DSG) reviewed the results of the survey.

The practice guideline report was circulated to members of the Practice Guidelines Coordinating Committee (PGCC) for review and approval. Ten of 11 members of the PGCC returned ballots. Eight members approved the practice guideline as written, and two members approved the guideline conditional on the Gastrointestinal Cancer DSG addressing specific concerns.

The practice guideline report was subsequently approved by the Gastrointestinal Cancer DSG and the Practice Guidelines Coordinating Committee.

2004 Update

Based on new evidence that was published after the original practice guideline was completed, the Gastrointestinal Cancer DSG decided to modify the qualifying statements. The updated qualifying statement was not distributed to practitioners, as the Gastrointestinal DSG considered the modification minor.

The intent of treatment of locally advanced pancreatic cancer is palliation in symptomatic patients and prolongation of life in medically suitable cases. The following options are appropriate:

• For medically suitable patients, current conventional practice is to offer combined chemotherapy and radiotherapy.
• Outside a clinical trial, 5-fluorouracil (5-FU) given as bolus or infusion is the preferred chemotherapeutic agent to combine with radiotherapy. The optimal mode and duration of 5-fluorouracil delivery is unclear; however, infusional therapy appears to give better treatment outcome.

None provided

The recommendations are supported by evidence-based practice guidelines, meta-analyses, and randomized controlled trials.

Provision of optimal treatment for patients with locally advanced (unresectable but non-metastatic) pancreatic cancer with improved patient outcomes (e.g., overall survival, disease-free survival, local control, adverse effects and quality of life

Combination 5-fluorouracil (FU) and radiation is generally well tolerated; however, severe vomiting, mucositis, and leukopenia can occur in about 5% of patients. Although not superior to 5-fluorouracil in efficacy, other chemotherapeutic regimens appear to be more toxic.

Original Guideline

• Specific anti-cancer treatments (such as resection, chemotherapy, and radiation) may be supplemented with supportive care (such as pain control, nutritional support, biliary stenting, and bowel decompression as needed) if appropriate.
• The evidence on which current conventional practice is based is relatively weak.
• Chemotherapy alone with gemcitabine is an acceptable alternative.
• Care has been taken in the preparation of the information contained in this document. Nonetheless, any person seeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical circumstances or seek out the supervision of a qualified clinician. Cancer Care Ontario makes no representation or warranties of any kind whatsoever regarding their content or use or application and disclaims any responsibility for their application or use in any way.

2004 Update

• Supportive care alone is not recommended in patients who are medically suitable for chemotherapy and radiation treatment.

An implementation strategy was not provided.

End of Life Care
Living with Illness

Effectiveness

• Gastrointestinal Cancer Disease Site Group. Earle CC, Agboola O, Maroun J, Zuraw L. The treatment of locally advanced pancreatic cancer [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2004 Feb 20 [online update]. 17 p. (Practice guideline report; no. 2-7). [29 references]

Not applicable: The guideline was not adapted from another source.

2002 June 10 (revised 2004 Feb 20)

Program in Evidence-based Care - State/Local Government Agency [Non-U.S.]

The Practice Guidelines Initiative (PGI) is the main project of the Program in Evidence-based Care (PEBC), a Province of Ontario initiative sponsored by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care.

Cancer Care Ontario
Ontario Ministry of Health and Long-Term Care

Provincial Gastrointestinal Cancer Disease Site Group

Members of the Gastrointestinal Cancer Disease Site Group disclosed potential conflict of interest information.

None available

This summary was completed by ECRI on January 23, 2004. The information was verified by the guideline developer as of February 25, 2004. This NGC summary was updated by ECRI on September 24, 2004. The updated information was verified by the guideline developer on October 20, 2004.