Case:
60 years old male with no previous significant past medical history, he presented with epigastric pain, weight loss and lethargy. After multiple investigations including CT chest abdomen pelvis, MRCP, ERCP, he was diagnosed with locally advanced pancreatic cancer T4N1M0, the pancreatic mass was encasing the superior mesenteric artery (SMA), his case was discussed at the gastroenterology MDT. In view of the patient’s good performance status(PS), the initial management was for induction chemotherapy with FOLFIRINOX then for rescan after 3 months, if there was a good response to treatment, patient will proceed to have surgery or chemoradiotherapy(CRT) depending on the operability of the tumour. Unfortunately, after 3 months of induction chemotherapy, patient progressed with lung metastasis. Subsequently his performance status deteriorated (PS 2) and proceeded to palliative chemotherapy with single agent gemcitabine, subsequent to 3cycles of chemotherapy, patients died with disease progression. In this essay; I will outline some of the evidence for induction chemotherapy in locally advanced pancreatic cancer (LAPC) and the different lines of palliative chemotherapy, additionally I will try to outline some of the mechanism of resistance to chemotherapy in pancreatic cancer. Introduction: Pancreatic cancer is the fourth commonest cause of cancer mortality in the UK. There are about 8800 new cases of pancreatic cancer in the UK each year and 8700 die from this disease.1 Less than 20%of patients has respectable disease at diagnosis, that means about 80%of patients have either locally advanced disease that preclude them from curative resection or they have metastatic disease. These patients have extremely poor prognosis.2 Unfortunately pancreatic cancer is rapidly and inevitably fatal with a 5 year survival of 5% even in the respectable setting with one year survival of 20%. The prognosis of metastatic pancreatic cancer is about 6 months, LAPC is 12 months and respectable disease has a median survival of 24 months. This grim picture has driven researcher efforts into this disease in order to improve survival. Management of locally advanced pancreatic cancer(LAPC): Chemotherapy alone, primary chemoradiotherapy CRT or induction chemotherapy followed by CRT or surgery if disease is respectable are all possible but contentious options for patients in this group. …show more content…
However, chemotherapy remains the mainstay of treatment for this group of patients. And primary chemotherapy with or without consolidating CRT is the current treatment choice in the UK.1
(Chauffert et al 2008); randomised patient with a diagnosis of LAPC between upfront CRT with a dose of 60 Gy in 30 fractions delivered concurrently with cisplatin and 5FU followed by maintenance gemcitabine and the second arm were treated with gemcitabine alone. the median survival was shorter in the CRT arm 8.4 months comparing to gemcitabine arm with median survival of 14.3 months. The author concluded that CRT followed by gemcitabine was more toxic and less effective comparing to chemotherapy alone and this clearly shows the important of chemotherapy.3
In LAPC there is high risk of micrometastaic disease and disease progression occurs in 30-40%of patients within the first 3-4 months, therefore initiating chemotherapy is the preferred treatment over upfront CRT.3 Further studies, such as LAP07 which is a phase III trial which compared consolidation chemoradiotherapy 54Gy with continuing chemotherapy alone in patients who had received 4 cycles of induction chemotherapy with gemcitabine with or without erlotinib. This study showed that overall survival was
60 years old male with no previous significant past medical history, he presented with epigastric pain, weight loss and lethargy. After multiple investigations including CT chest abdomen pelvis, MRCP, ERCP, he was diagnosed with locally advanced pancreatic cancer T4N1M0, the pancreatic mass was encasing the superior mesenteric artery (SMA), his case was discussed at the gastroenterology MDT. In view of the patient’s good performance status(PS), the initial management was for induction chemotherapy with FOLFIRINOX then for rescan after 3 months, if there was a good response to treatment, patient will proceed to have surgery or chemoradiotherapy(CRT) depending on the operability of the tumour. Unfortunately, after 3 months of induction chemotherapy, patient progressed with lung metastasis. Subsequently his performance status deteriorated (PS 2) and proceeded to palliative chemotherapy with single agent gemcitabine, subsequent to 3cycles of chemotherapy, patients died with disease progression. In this essay; I will outline some of the evidence for induction chemotherapy in locally advanced pancreatic cancer (LAPC) and the different lines of palliative chemotherapy, additionally I will try to outline some of the mechanism of resistance to chemotherapy in pancreatic cancer. Introduction: Pancreatic cancer is the fourth commonest cause of cancer mortality in the UK. There are about 8800 new cases of pancreatic cancer in the UK each year and 8700 die from this disease.1 Less than 20%of patients has respectable disease at diagnosis, that means about 80%of patients have either locally advanced disease that preclude them from curative resection or they have metastatic disease. These patients have extremely poor prognosis.2 Unfortunately pancreatic cancer is rapidly and inevitably fatal with a 5 year survival of 5% even in the respectable setting with one year survival of 20%. The prognosis of metastatic pancreatic cancer is about 6 months, LAPC is 12 months and respectable disease has a median survival of 24 months. This grim picture has driven researcher efforts into this disease in order to improve survival. Management of locally advanced pancreatic cancer(LAPC): Chemotherapy alone, primary chemoradiotherapy CRT or induction chemotherapy followed by CRT or surgery if disease is respectable are all possible but contentious options for patients in this group. …show more content…
However, chemotherapy remains the mainstay of treatment for this group of patients. And primary chemotherapy with or without consolidating CRT is the current treatment choice in the UK.1
(Chauffert et al 2008); randomised patient with a diagnosis of LAPC between upfront CRT with a dose of 60 Gy in 30 fractions delivered concurrently with cisplatin and 5FU followed by maintenance gemcitabine and the second arm were treated with gemcitabine alone. the median survival was shorter in the CRT arm 8.4 months comparing to gemcitabine arm with median survival of 14.3 months. The author concluded that CRT followed by gemcitabine was more toxic and less effective comparing to chemotherapy alone and this clearly shows the important of chemotherapy.3
In LAPC there is high risk of micrometastaic disease and disease progression occurs in 30-40%of patients within the first 3-4 months, therefore initiating chemotherapy is the preferred treatment over upfront CRT.3 Further studies, such as LAP07 which is a phase III trial which compared consolidation chemoradiotherapy 54Gy with continuing chemotherapy alone in patients who had received 4 cycles of induction chemotherapy with gemcitabine with or without erlotinib. This study showed that overall survival was