Systemic chemotherapy of metastatic colorectal cancer

1
Systemic chemotherapy of metastatic colorectal
cancer

• ????????
• 96.10.1

2
Introduction

• Most patients with metastatic colorectal cancer
  (MCRC) develop the tumor recurrence months to
  years after initial treatment.
• Cure is not possible for most patients with MCRC,
  although some patients who have limited
  involvement (particularly liver) may be cured by
  further surgery, for others, chemotherapy (C/T)
  is the most appropriate option.
• C/T doesn't cure MCRC, but it can improve
  symptoms and prolong life.

3
Surgery for resectable advanced disease

• Surgery can be considered for patients whose
  colorectal ca has spread in a limited way outside
  of the intestine, to an area such as the liver.
• Intravenous C/T might permit some patients who
  have liver metastasis that are initially
  unresectable or borderline resectable to have
  successful surgery.

4
Chemotherapy V.S best supportive care

• The median overall survival for patients with
  unresectable MCRC who receive supportive care
  alone is approximately five to six months.
• Although systemic C/T has not significantly
  improved five-year survival rates, it has
  produced meaningful improvements in median
  survival and progression-free survival (PFS).
• These benefits are most pronounced with regimens
  containing Irinotecan or Oxaliplatin in
  combination with 5-FU median survival durations
  consistently approach 2024months.

5
Timing to institute chemotherapy

• Many patients with MCRC are asymptomatic. The
  value of early C/T versus treatment deferral
  until symptoms develop is controversial.
• The only randomized trials directly addressing
  this issue have studied patients receiving
  leucovorin 5-FU
• Trial 1Earlier treatment was associated with an
  improvement in median survival (14 versus 9
  months), symptom-free interval, and PFS.
• Trial 2The two-month benefit in median overall
  survival with early treatment (13 versus 11
  months) was not statistically significant.
• In the U.S.A, many patients institute treatment
  at a time when they are asymptomatic.

6
Chemotherapy for unresectable disease

• Conventional chemotherapy
• 5-fluororacil(5-FU)
• Xeloda( orally active 5-FU-like drugs)
• Oxaliplatin( Eloxatin)
• Irinotecan( Campto)
• Target therapies
• Bevacizumab ( Avastin)binds the vascular
  endothelial growth factor ( VEGF).
• Cetuximab ( Erbitux) targets the epidermal
  growth factor receptor ( EGFR).
• Pantumumab ( Vectibix) targets the EGFR, in a
  different way than Erbitux.

7
Assessment during therapy

• CT scan, PET ( every 23 cycles)
• CEA ( every 13months)
• Persistently rising CEA levels should prompt
  restaging, but suggest disease progression and
  the need for an alternative treatment strategy.
• Caution should be used when interpreting a rising
  CEA level during the first 4 to 6 weeks of a new
  therapy, since spurious early elevation in serum
  CEA may occur, especially after Oxaliplatin.

8
First- line chemotherapy

• FOLFOX( Oxaliplatin plus 5-FU and leucovorin Q2W)
• FOLFIRI( Irinotecan plus 5-FU and leucovorin
  Q2W)
• Patients should have a central line and a
  portable IV pump.
• In the U.S.A, most patients are offered first-
  line FOLFOX, and FOLFIRI is reserved for second-
  line therapy.
• Xeloda Oxaliplatin( ????IV pump ?)( ??????)
• Benefit of adding Avastin
• A significant higher response, it prolongs
  survival.
• Patients who cant tolerate Irinotecan or
  Oxaliplatin
• Less toxic alternative 5-FU leucovorin(
  Avastin)

9
Second- line chemotherapy

• If FOLFOX( or Xeloda Oxaliplatin) plus Avastin
  was the first line regimen, the patient is
  usually switched to FOLFIRI with or without
  Avastin.
• FOLFIRI Avastin ? FOLFOX( or Xeloda
  Oxaliplatin) with or without Avastin.
• Adding Erbitux to Irinotecan can shrink tumors in
  patients who stop responding FOLFIRI regimen.
• Erbitux plus irinotecan is used for third- line
  therapy after failure of both FOLFOX and FOLFIRI.
• It is also used as second line therapy if there
  is progression on FOLFIRI plus Avastin.

10
Chemotherapy side effects
11
Chemotherapy side effects( ?)
12
Management of side effects

• Neurotoxicity of Oxaliplatin
• Lengthening the infusion duration can prevent
  the recurrence of pseudolaryngospasm.
• Hypersensitive reactions( rash, fever, ocular and
  respiratory symptoms) of Oxaliplatin
• Adding premedication of diphenhydramine( Vena)
  and steroids
• Decreas the dose or lengthen the infusion
  duration

13
Management of side effects

• Impair wound healing, GI perforation and fistula
  formation of Avastin
• 28 days between surgery and Avastin therapy
• Proteinuria intermittent U/A during Avastin
• Hypersensitive reactions of Erbitux
• Premedication with an H1 Antagonist
• ( dihenhydramin 50mg IV), infusion ratelt5ml/min
• Magnesium wasting syndrome of Erbitux
• Monitor serum magnesium level during and
  following ( for at least 8 weeks) therapy.

14
Summary

• Initial C/T may increase the number of patients
  with isolated hepatic metastases who are
  potentially eligible for resection.
• Although the long-term prognosis is poor for
  patients with unresectable MCRC, palliative C/T
  can relieve symptoms and prolong survival.
• The most active drugs for MCRC are the
  fluoropyrimidines, oxaliplatin, and irinotecan.
  The approval of the therapeutic monoclonal
  antibodies, bevacizumab, cetuximab, and
  panitumumab has increased the number of
  therapeutic options.
• However, the optimal combination and sequencing
  of all of these agents are unresolved issues.

15

• Thanks for your attention!