Keywords
Acute pancreatitis - carboplatin - chemotherapy - gemcitabine - pemetrexed
Introduction
Acute pancreatitis is a common cause of acute abdomen, usually seen by the emergency
physicians. The condition usually manifests with symptoms of severe upper abdominal
pain radiating to back, nausea, vomiting, and fever. The most common causes of acute
pancreatitis include alcoholism, gallstones, hypertriglyceridemia, and drugs. Drug-induced
pancreatitis is one of the rarer causes of acute pancreatitis.[1] Many chemotherapy drugs are known to cause acute pancreatitis. Common causes include
azathioprine 6 MP, capecitabine, paclitaxel, vinorelbine, and ifosfamide.[2]
[3]
[4]
[5]
[6]
[7] Many other anticancer drugs have been found to produce acute pancreatitis including
newer agents such as nivolumab and ipilimumab.[8]
Case Report
A 60-year-old male presented to HealthCare Global Hospital, Bengaluru, (India), with
complaints of dry cough of 5-month duration. There was a gradual increase in the intensity
of cough over 5 months. The patient was a known hypertensive and was on regular antihypertensive
medications for the past 5 years. He had a performance status of 1/5 according to
the Eastern Cooperative Oncology Group scale of performance status. A CT scan was
performed elsewhere had revealed a mass in the anterior segment of left upper lobe
of the lung. A PET-CT scan was performed our hospital revealed 6 cm × 4.3 cm × 4.1
cm metabolically active enhancing lesion in the anterior segment of left upper lobe
infiltrating mediastinum, inferior vena cava, and anterior pleura. There were also
enlarged left hilar, aortopulmonary window, subcarinal, and paratracheal lymph nodes.
According to the TNM staging system, the patient was diagnosed to have IIIB disease.
A lung biopsy was done and histopathological examination revealed features suggestive
of non-small cell lung cancer favoring adenocarcinoma. Investigations to detect EGFR
mutations were sent. A chemotherapy regimen consisting of Inj Pemetrexed 500 mg/m
2 and Inj Carboplatin AUC 5 Q 21 days for four cycles was planned. The patient received
his first cycle of chemotherapy on June 29, 2017. After 2 weeks following the first
cycle on July 13, 2017, the patient presented to emergency with severe upper abdominal
pain radiating to back and several episodes of vomiting. Investigations revealed increased
amylase levels (1807) and lipase levels (10719) [Table 1]. Causes of acute pancreatitis such as alcoholism, gallstones, hypertriglyceridemia,
and biliary interventions were ruled out by detailed history, examination, and necessary
investigations. He was treated with intravenous fluids, antacids, analgesics, and
other supportive measures. He was treated conservatively. Necessary imaging studies
were performed which revealed uncomplicated nature of acute pancreatitis. After about
5 days of treatment, the patient recovered symptomatically and also lipase levels
reverted to normal levels. Since no etiology could be found despite extensive investigations,
it was presumed that acute pancreatitis could have been secondary to chemotherapy.
Hence, it was decided to exclude pemetrexed from subsequent cycles.
Table 1
Serial values of pancreatic enzyme levels
|
1st cycle
|
3rd cycle
|
|
15st day
|
20th day
|
3rd day
|
8th day
|
|
Amylase
|
1807
|
100
|
3108
|
96
|
|
Lipase
|
10,719
|
218
|
37,872
|
196
|
The patient was initiated on Injection paclitaxel for the next chemotherapy cycle
in place of Inj pemetrexed. However, the patient developed a severe hypersensitivity
reaction to Injection Paclitaxel. Hence, Inj paclitaxel was discontinued and the patient
was given only Injection Carboplatin. The patient tolerated the second cycle and had
no supportive care issues.
The patient was started on the third cycle chemotherapy with Injection gemcitabine
and Injection carboplatin. He developed acute abdominal pain with multiple episodes
of vomiting following D8 of third cycle. Acute pancreatitis was suspected and necessary
investigations were done. The serum lipase levels were high (37872) [Table 1]. CT scan of the abdomen showed swelling of the head of pancreas with peripancreatic
collection [Figure 1]. Extensive investigations were done to rule out other more common causes of acute
pancreatitis. He was managed conservatively. He recovered following these measures
and was discharged after 5 days. Since no known cause of acute pancreatitis was found,
it was suspected that both episodes were due to chemotherapy agents. The patient was
advised radiation therapy as it was assumed that further chemotherapy could trigger
recurrent and complicated acute pancreatitis episodes.
Figure 1: The head of pancreas is bulky with moderate peripancreatic fat stranding,
multiple heterogeneous attenuating peripancreatic, and paraduodenal areas with focal
internal fat attenuation–suggestive of acute focal pancreatitis with multiple peripancreatic
and paraduodenal necrotic collections. There was no evidence of ascites or vascular
complications. The modified computed tomography severity index was four
Discussion
Drug-induced acute pancreatitis is a well-known and well-documented entity. Usually,
it is a diagnosis of exclusion and diagnosis is made after excluding all other causes
of acute pancreatitis. Chemotherapy-induced acute pancreatitis is rare and has been
documented with few drugs.
In our patient, the predisposing factors were obesity and male gender.[9] He developed acute pancreatitis after a latent period of about 2 weeks following
chemotherapy in the first episode and about 3 days following chemotherapy in the second
episode. This latency period is consistent with the published data regarding the same.[10]
[11] The patient also had mild pancreatitis which resolved with conservative measures;
however, he requires long-term follow-up to observe for development for complications
such as pancreatic pseudocyst.
Pemetrexed has been shown cause acute pancreatitis in some postmarketing surveillance
reports. There are few case reports and case series reporting acute pancreatitis with
platinum agents. Oxaliplatin and cisplatin appeared to produce acute pancreatitis
more than carboplatin. In fact, only one case of a patient with breast cancer treated
with carboplatin developing acute pancreatitis has been reported.[12] There has been one case report of acute pancreatitis developing following administration
of gemcitabine and cisplatin combination chemotherapy.[13] Our patient appeared to have developed acute pancreatitis following administration
of all three agents, namely pemetrexed, carboplatin, and gemcitabine. Ours is the
first reported case revealing acute pancreatitis following pemetrexed and the second
reported case following carboplatin and gemcitabine.
Conclusions
Although some chemotherapy agents are implicated in the development of acute pancreatitis
commonly such as capecitabine, paclitaxel, vinorelbine, azathioprine, and L-asparaginase,
there are other agents which can rarely cause this dreaded condition. Pemetrexed,
carboplatin, and gemcitabine are few such agents. There should be a high index of
suspicion when diagnosing acute pancreatitis caused by these agents. Care should also
be taken to rule out other major causes of acute pancreatitis before attributing the
etiology to the chemotherapeutic agent.
