168 Journal of Pain and Symptom Management Vol. 3 No. 4 Fall 1988

Pain in Pancreatic Cancer: A Medical Oncologist’s View John Horton, MB, ChB Albany Medical College, Albany, New York

Presenting Comfdaints The presenting symptoms of pancreatic

cancer deserve reemphasis. Seventy-five per- cent of patients have cancer of the head of the pancreas. Most of these patients develop jaun- dice, and this can clearly affect the metabolism of drugs excreted through the liver. Anorexia, nausea and vomiting, and weakness are com- mon presenting complaints and many patients are depressed or anxious. Those patients with cancer of the body and tail of the pancreas most often present with weight loss, nausea and vom- iting, anorexia, weakness and pain. Most of the discomforts associated with diagnostic proce- dures are relatively minor except for those from laparotomy which is still needed for diagnosis in many instances. Many patients understand poorly the reasons for many of the studies that are performed, and painful complications from such studies sometimes occur.

Clinical Course

The course of pancreatic cancer is character- ized by clinical wasting and pain. Survival is most often measured in a few months after diagnosis. Local and regional spread may ob- struct various organs and infiltrate surrounding structures. This can produce pain as well as other clinical problems. Retroperitoneal infil- tration is particularly important since it may be the most significant cause of pain. Infections, particularly ascending cholangitis, can be devas- tating. Cholangitis is related to obstruction, is often recurrent, and may require changing the stents inserted to provide internal biliary drain- age. Parenteral antibiotics and hospitalization are often needed for control. The liver is the

most significant site for distant metastases. This can result in wasting and altered metabolism of drugs, and may itself produce pain. Peritoneal metastases and metastases to bone and other areas may also occur.

Factors Afecting Pain Control Clinical observation suggests that a variety of

factors may affect pain severity and control in patients with pancreatic cancer (Table 1). These include a history of previous pain, fa- tigue, fever, insomnia, anorexia, nausea and vomiting, weakness, malaise, anxiety and de- pression. The last two factors occur more fre- quently in patients with pancreatic cancer than in those with cancer of other intraab- dominal sites, perhaps due to the presence of jaundice or some poorly understood paracrine effect. In addition to these factors, others may also influence the effectiveness, side effects, toxicity and tolerance of analgesic drugs. The selection of drug, its dosage and scheduling are obviously important, but some factors, such as absorption, metabolism and excretion are less appreciated. These factors rely on proper organ function and may be adversely affected

Table 1 Factors that Influence Pain and Pain Control in

Patients with Cancer of the Pancreas

1. Preexisting pain 2. Malnutrition:

anorexia, nausea, vomiting, diarrhea 3. Psychological and psychosocial:

fatigue, insomnia, malaise, weakness, anxiety, depression, isolation

4. Infection: fever and debility

0 U.S. Cancer Pain Relief Committee, 1988 Published by Elsevier, New York, New York 0885-3924/88/$3.50

Vol. 3 No. 4 Fall 1988 Pain in Pancreatic Cancer I69

by complications of pancreatic cancer that affect the gastrointestinal tract, liver and kidneys. Drug-drug interactions are also important issues to consider, since patients with pancreatic cancer may require a wide variety of drugs.

Medical Treatment Systemic antitumor chemotherapy may be

discussed in two categories, so-called standard chemotherapy and experimental therapy (Table 2). There is no uniformly effective che- motherapy for pancreatic cancer. Tumor shrinkage and symptomatic improvement occur in perhaps 10% of those in which it is used. Reports from institutions and groups perform- ing clinical trials of chemotherapy report objec- tive response rates in the 30%) to 40% range, but case selection is restricted to those patients who have the best performance status. The general community of medical oncologists treat a larger proportion of the population of pa- tients with pancreatic cancer, including many who have a poor performance status. Thus, overall response rates are less than those pub- lished.

There is little information about the associa- tion between chemotherapy, tumor response or remission, and pain relief. The majority of pa- tients who receive chemotherapy have pain. and medical oncologists generally believe that measurable tumor shrinkage is associated with some reduction of pain. Most patients treated with chemotherapy, however, will not experi- ence a tumor response.

It thus remains unclear that chemotherapy has an effect on pain in this situation, although a “placebo” effect may provide transitory bene- fit to some patients. In addition, the arbitrary definition of an “objective” tumor response usually requires greater than 50% reduction in measured tumor area. It is possible that shrink- age less than the arbitrary 50%,, i.e., not suffi- cient to be defined as an objective response, may also be associated with pain relief.

Side effects from chemotherapy are apprecia- ble (Table 3). As an example, one can consider the most standard chemotherapy, which in- cludes 5-fluorouracil, doxorubicin and mitomy- tin C; this so-called FAM regimen requires in- travenous injections given several times a month. Most patients experience nausea and

Table 2* Antitumor Effects (Tumor Remissions) of Selected Chemotherapeutic Agents and Combinations in Advanced

Pancreatic Cancer

A. Single agents: Patients

Agent Evaluated Response, %

5-fluorourdcil streptozotocin mitomycin C semustine doxorubicin methotrexate carmustine etoposide

“8 36 21

!I 7 4 0 0

B. Combination chemotherapy: Patients

Agents Evaluated Kesponse, %

54uorouracil doxorubicin mitomycin C, streptozotocin (FAM-S)

5-fluorouracil, doxorubicin, mitomycin C (FAM)

streptozotocin, mitomycin C, 5-fluorouracil (SMF)

*Modified from Horton J. Management of cancer of the pancreas. Current Concepts in Oncology 1987; 9:3-7.

170 Horton Journal of Pain and Symptom Management

Table ? Significant Side Effects of Systemic

Antitumor Therapy

1. Cytotoxic combination chemotherapy: anorexia, nausea, vomiting, malaise, weakness, marrow sup- pression:

anemia, risk of infection or bleeding, alopecia, drug infiltration into soft tissues

2. Biologic res dromes, P.

onse modifiers: fever, flu-like syn- ma arse, depression, increased capillary

permeability, fluid retention, hypotension, organ toxicities:

marrow, liver, CNS, renal, other

vomiting and feel generally ill after each injec- tion, sometimes for days or weeks. Alopecia is universal, weight loss usually occurs, and hema- tologic effects are common. Paravenous infil- tration of mitomycin C or doxorubicin may occur, producing painful ulcerations that may need surgical excision.

There is recently a great deal of interest in new systemic approaches for the treatment of pancreatic cancer, such as the biologic response modifiers interleukin, interferons and tumor necrosis factor. These treatments are also gen- erally associated with considerable toxicity. After treatment with an interferon, for exam- ple, most patients feel ill, are febrile, and have a sense of having the flu. Confusion, paresthe- sias, seizures, and a host of other complications can occur, each potentially complicating pain control.

Thus, the medical management of pancreatic cancer is inadequate and can compound the challenge of pain management in these pa- tients. New chemotherapeutic agents are under investigation, but it is likely that each will be as- sociated with a spectrum of toxicity that can augment the pain and enhance the suffering so common in this disease.