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Pain in pancreatic cancer: A medical oncologist's view
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 percent of patients have cancer of the head of the pancreas. Most of these patients develop jaundice, and this can clearly affect the metabolism of drugs excreted through the liver. Anorexia, nausea and vomiting, and weakness are common 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 vomiting, anorexia, weakness and pain. Most of the discomforts associated with diagnostic procedures 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 characterized by clinical wasting and pain. Survival is most often measured in a few months after diagnosis. Local and regional spread may obstruct various organs and infiltrate surrounding structures. This can produce pain as well as other clinical problems. Retroperitoneal infiltration is particularly important since it may be the most significant cause of pain. Infections, particularly ascending cholangitis, can be devastating. Cholangitis is related to obstruction, is often recurrent, and may require changing the stents inserted to provide internal biliary drainage. Parenteral antibiotics and hospitalization are often needed for control. The liver is the 0 U.S. Cancer Pain Relief Committee, 1988 Published by Elsevier, New York, New York
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, fatigue, fever, insomnia, anorexia, nausea and vomiting, weakness, malaise, anxiety and depression. The last two factors occur more frequently in patients with pancreatic cancer than in those with cancer of other intraabdominal 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
0885-3924/88/$3.50
Pain in Pancreatic Cancer
Vol. 3 No. 4 Fall 1988
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 experimental chemotherapy and therapy (Table 2). There is no uniformly effective chemotherapy for pancreatic cancer. Tumor shrinkage and symptomatic improvement occur in perhaps 10% of those in which it is used. Reports from institutions and groups performing clinical trials of chemotherapy report objective 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 patients with pancreatic cancer, including many who have a poor performance status. Thus, overall response rates are less than those published.
There is little information about the association between chemotherapy, tumor response or remission, and pain relief. The majority of patients 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 experience a tumor response. It thus remains unclear that chemotherapy has an effect on pain in this situation, although a “placebo” effect may provide transitory benefit 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 shrinkage less than the arbitrary 50%,, i.e., not sufficient to be defined as an objective response, may also be associated with pain relief. Side effects from chemotherapy are appreciable (Table 3). As an example, one can consider the most standard chemotherapy, which includes 5-fluorouracil, doxorubicin and mitomytin C; this so-called FAM regimen requires intravenous injections given several times a month. Most patients experience nausea and
Table 2* Antitumor Effects (Tumor Remissions) of Selected Chemotherapeutic Pancreatic Cancer A.
Single
I69
Agents and Combinations in Advanced
agents:
Patients Agent
Evaluated
Response,
%
“8 36 21
5-fluorourdcil streptozotocin mitomycin C semustine doxorubicin methotrexate carmustine etoposide
!I
7 4 0 0
B. Combination chemotherapy:
Patients Agents
Evaluated
54uorouracil doxorubicin mitomycin streptozotocin (FAM-S) 5-fluorouracil, doxorubicin, mitomycin C (FAM) streptozotocin, mitomycin C, 5-fluorouracil (SMF) *Modified 9:3-7.
from
Horton
Kesponse, %
C,
J. Management
of cancer
of the pancreas.
Current
Concepts
in Oncology
1987;
Horton
170
Table ? Significant Side Effects of Systemic Antitumor Therapy
1. Cytotoxic combination chemotherapy: anorexia, nausea, vomiting, malaise, weakness, marrow suppression: anemia, risk of infection or bleeding, alopecia, drug infiltration into soft tissues 2. Biologic res onse modifiers: fever, flu-like syndromes, ma P. arse, depression, increased capillary permeability, fluid retention, hypotension, organ toxicities: marrow, liver, CNS, renal, other
vomiting and feel generally ill after each injection, sometimes for days or weeks. Alopecia is universal, weight loss usually occurs, and hematologic effects are common. Paravenous infiltration of mitomycin C or doxorubicin may occur, producing painful ulcerations that may need surgical excision.
Journal of Pain and Symptom Management
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 generally associated with considerable toxicity. After treatment with an interferon, for example, most patients feel ill, are febrile, and have a sense of having the flu. Confusion, paresthesias, 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 patients. New chemotherapeutic agents are under investigation, but it is likely that each will be associated with a spectrum of toxicity that can augment the pain and enhance the suffering so common in this disease.
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 percent of patients have cancer of the head of the pancreas. Most of these patients develop jaundice, and this can clearly affect the metabolism of drugs excreted through the liver. Anorexia, nausea and vomiting, and weakness are common 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 vomiting, anorexia, weakness and pain. Most of the discomforts associated with diagnostic procedures 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 characterized by clinical wasting and pain. Survival is most often measured in a few months after diagnosis. Local and regional spread may obstruct various organs and infiltrate surrounding structures. This can produce pain as well as other clinical problems. Retroperitoneal infiltration is particularly important since it may be the most significant cause of pain. Infections, particularly ascending cholangitis, can be devastating. Cholangitis is related to obstruction, is often recurrent, and may require changing the stents inserted to provide internal biliary drainage. Parenteral antibiotics and hospitalization are often needed for control. The liver is the 0 U.S. Cancer Pain Relief Committee, 1988 Published by Elsevier, New York, New York
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, fatigue, fever, insomnia, anorexia, nausea and vomiting, weakness, malaise, anxiety and depression. The last two factors occur more frequently in patients with pancreatic cancer than in those with cancer of other intraabdominal 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
0885-3924/88/$3.50
Pain in Pancreatic Cancer
Vol. 3 No. 4 Fall 1988
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 experimental chemotherapy and therapy (Table 2). There is no uniformly effective chemotherapy for pancreatic cancer. Tumor shrinkage and symptomatic improvement occur in perhaps 10% of those in which it is used. Reports from institutions and groups performing clinical trials of chemotherapy report objective 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 patients with pancreatic cancer, including many who have a poor performance status. Thus, overall response rates are less than those published.
There is little information about the association between chemotherapy, tumor response or remission, and pain relief. The majority of patients 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 experience a tumor response. It thus remains unclear that chemotherapy has an effect on pain in this situation, although a “placebo” effect may provide transitory benefit 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 shrinkage less than the arbitrary 50%,, i.e., not sufficient to be defined as an objective response, may also be associated with pain relief. Side effects from chemotherapy are appreciable (Table 3). As an example, one can consider the most standard chemotherapy, which includes 5-fluorouracil, doxorubicin and mitomytin C; this so-called FAM regimen requires intravenous injections given several times a month. Most patients experience nausea and
Table 2* Antitumor Effects (Tumor Remissions) of Selected Chemotherapeutic Pancreatic Cancer A.
Single
I69
Agents and Combinations in Advanced
agents:
Patients Agent
Evaluated
Response,
%
“8 36 21
5-fluorourdcil streptozotocin mitomycin C semustine doxorubicin methotrexate carmustine etoposide
!I
7 4 0 0
B. Combination chemotherapy:
Patients Agents
Evaluated
54uorouracil doxorubicin mitomycin streptozotocin (FAM-S) 5-fluorouracil, doxorubicin, mitomycin C (FAM) streptozotocin, mitomycin C, 5-fluorouracil (SMF) *Modified 9:3-7.
from
Horton
Kesponse, %
C,
J. Management
of cancer
of the pancreas.
Current
Concepts
in Oncology
1987;
Horton
170
Table ? Significant Side Effects of Systemic Antitumor Therapy
1. Cytotoxic combination chemotherapy: anorexia, nausea, vomiting, malaise, weakness, marrow suppression: anemia, risk of infection or bleeding, alopecia, drug infiltration into soft tissues 2. Biologic res onse modifiers: fever, flu-like syndromes, ma P. arse, depression, increased capillary permeability, fluid retention, hypotension, organ toxicities: marrow, liver, CNS, renal, other
vomiting and feel generally ill after each injection, sometimes for days or weeks. Alopecia is universal, weight loss usually occurs, and hematologic effects are common. Paravenous infiltration of mitomycin C or doxorubicin may occur, producing painful ulcerations that may need surgical excision.
Journal of Pain and Symptom Management
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 generally associated with considerable toxicity. After treatment with an interferon, for example, most patients feel ill, are febrile, and have a sense of having the flu. Confusion, paresthesias, 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 patients. New chemotherapeutic agents are under investigation, but it is likely that each will be associated with a spectrum of toxicity that can augment the pain and enhance the suffering so common in this disease.