Treatment of gastric carcinoma

1. GASTRIC CARCINOMA
- Treatment
By,
Dr.S. Preethiya

2. - Systemic therapy
- Immunotherapy
- Radiotherapy
- Palliative care

3. Systemic therapy
● Recommended for advanced esophageal, EGJ adenocarcinoma and gastric
adenocarcinoma
● Localized gastric cancer - perioperative or postoperative chemotherapy +
chemoradiation
● Following D2 lymph node resection - postoperative chemotherapy
● Two drug regimen - advanced disease (lower toxicity )
● Three drug regimen - medically fit patients with good PS and access to
frequent toxicity evaluation

5. PREOPERATIVE
CHEMOTHERAPY
3 cycles preoperatively &
3 cycles post operatively
CHEMORADIATION
Paclitaxel &
carboplatin
Recommended
1.5-FU & oxaliplatin
2. 5-FU and cisplatin
3. Fluoropyrimidine (5-FU or
capecitabine ) & paclitaxel
OTHER
1.5-FU and
cisplatin
RECOMMENDED
1. Fluoropyrimidine and
oxaliplatin
2. 5-FU , leucovorin ,
oxaliplatin and docetaxel
(FLOT )

6. Oxaliplatin 85 mg/m2 IV on day 1
Leucovorin 400 mg/m2 IV on day 1
5-FU 400mg/m2 IV on day 1
5-FU 1200 mg/m2 IV continuous
infusion over
24 hrs daily on
days 1 and 2
Oxaliplatin 85 mg/m2 IV on day 11
Leucovorin 200mg/m2 IV on day 1
Fluorouracil 2600mg/m2 IV
Continuous
infusion over
24 hrs on
day 1
Preoperative chemotherapy
Fluoropyrimidine and oxaliplatin - 3 cycles preop and 3 cycles
postop
14 days cycle 14 days cycle

7. Capecitabine 1000mg/m2 Per-oral BD on days 1-
14
Oxaliplatin 130 mg/m2 IV on day 1
21 days cycle

8. Fluorouracil , leucovorin , oxaliplatin and
docetaxel (FLOT )
➔ 4 cycles preoperatively and 4 cycles post operatively ( cycled
every 14 days)
◆ 5-FU (2600 mg/m2 )/ IV continuous infusion over 24 hrs
on day 1
◆ Leucovorin (200 mg/m2)/ IV on day 1
◆ Oxaliplatin (85 mg/m2 )/ IV on day 1
◆ Docetaxel (50 mg/m2)/ IV on day 1

9. Preoperative Chemoradiation
Fluorouracil and
oxaliplatin( every 14
days for 3 cycles with
radiation )
1. Oxaliplatin (85 mg/m2) /
IV on day 1
2. Leucovorin (400 mg/m2)
/ - day 1
3. 5-FU (400 mg/m2)/ IV -
day 1
5-FU (800 mg/m2) / IV
continuous infusion on
day 1 and 2
Capecitabine &
Oxaliplatin
1. Oxaliplatin (85 mg/m2)/
IV - Days 1,15, 29 - 3
doses
2. Capecitabine ( 625
mg/m2) /
Per-oral
BD
On days 1-5 for 5 weeks
Fluorouracil & cisplatine (
35 day cycle)
1. Cisplatin - 75-100 mg/m2 -
days 1 & 29
2. 5-FU (750 - 1000 mg/m2 )/ IV
continuous infusion over 24
hrs daily on days 1-4 and 29-
32
Or (cycled every 21 days for 2
cycles )
1. Cisplatin (15 mg/m2 )/ IV -
days 1-5
2. 5-FU ( 800 mg/m2)/ IV
continuous infusion on days 1-
5

10. Capecitabine & Cisplatin (weekly for
5 weeks )
1. Cisplatin (30 mg/m2) / IV - day 1
2. Capecitabine - (800 mg/m2) / PO -
BD
Day 1-5
Paclitxel and Fluoropyrimidine (
weekly for 5 weeks)
1. Paclitaxel (45-50 mg/m2 ) / IV
/day 1 weekly
2. 5-FU (300 mg/m2) / IV
continuous infusion / days 1-5
Or
1. Paclitaxel (45-50 mg/m2) / IV /
day 1
2. Capecitabine (625 - 825 mg/m2)
/PO -BD - days 1-5

11. Post operative
● Chemoradiation (pts . received less than D2 LN dissection )
❖ Fluoropyrimidine (infusion 5-FU or capecitabine ) before and after
Fluoropyrimidine based chemoradiation
1 cycle before and 2 cycles after chemoradiation (every 21 days)
Capecitabine ( 750-1000 mg/m2) - peroral , BD on days 1- 14
With radiation - capecitabine (625 - 825 mg/m2) ,PO, BD on days 1-5 (weekly
for 5 weeks )
2 cycles before and 4 cycles after chemoradiation ( every 14 days )
Leucovorin ( 400 mg/m2) /IV - day 1
5 -FU (400 mg/m2) / IV - day 1
5-FU (1200 mg/m2) /IV -continuous infusion over 24 hrs daily on days 1 and 2

12. With radiation : 5-FU (200-250 mg/m2 / IV continuous infusion -
24 hrs daily on days 1-5 ( weekly for 5 wks )
● Chemotherapy (pts have undergone D2 LN dissection )
➔ Capecitabine and Oxaliplatin ( every 21 days - 8 cycles)
Capecitabine (1000 mg/m2) / peroral - BD on days 1-14
Oxaliplatin ( 130 mg/m2) / IV on day 1
● Chemoradiation for unresectable disease
★ Fluorouracil and Oxaliplatin
★ Fluorouracil and Cisplatin
★ Fluoropyrimidine ( Fluorouracil or capecitabine ) and paclitaxel

13. Unresectable locally advanced , recurrent or
metastatic disease ( local therapy not indicated )
First line therapy - Two drug regimen
Fluoropyrimidine & Oxaliplatin
● Every 14 days
Oxaliplatin ( 85 mg/m2) / IV - day 1
Leucovorin ( 400 mg/m2) /IV - day 1
5 - FU ( 400 mg/m2) / IV - day 1
5 - FU ( 1200 mg/m2) - IV - continuous infusion over
24 hrs - day 1 and day 2
● Every 14 days
Oxaliplatin ( 85 mg/m2) / IV - day 1
Leucovorin ( 200 mg/m2) /IV - day 1
5 - FU ( 2600 mg/m2) - IV - continuous infusion over
24 hrs - day 1 and day 2
● Every 21 days
Capecitabine ( 1000mg/m2) - peroral - BD - day
1-14
Oxaliplatin (130 mg/m2) - IV - day 1
Trastuzumab ( with chemotherapy )
8 mg/kg - IV loading dose - day 1 ------->
6 mg/kg - IV every 21 days
Or
6 mg/kg - IV loading dose on day 1 of cycle , -----
-> 4 mg/kg IV every 14 days .

14. Fluoropyrimidine & cisplatin
Every 28 days cycle
Cisplatin ( 75-100 mg/m2) - day 1
5 - FU (750-1000 mg/m2) / IV
continuous infusion over 24 hrs daily
on days 1-14
Every 14 days cycle
Cisplatin ( 50 mg/m2) - day 1
Leucovorin (200 mg/m2) / IV - day 1
5 - FU (2000 mg/m2) / IV continuous
infusion over 24 hrs daily on days 1
Every 21 days
Cisplatin (80 mg/m2) / IV - daily
on day 1
Capecitabine (1000 mg/m2) -
peroral - BD on days 1-14

15. Second - line and subsequent therapy
Preferred regimen
1. Ramucirumab & paclitaxel (every 28 days )
Ramucirumab ( 8mg/kg) / IV - days 1 and 15
Paclitaxel ( 80 mg/kg) - days 1,8 and 15
1. Taxane
Docetaxel (75-100mg/m2) / IV - day 1 ( every 21 days )
Paclitaxel (135-200 mg/m2) / IV - day 1( every 21
days)
Paclitaxel (80 mg/m2) / IV - day 1 weekly ( every 28
days)
Paclitaxel (80 mg/m2) / IV - day 1 , 8 and 15 ( every 28
days)
3. Irinotecan
250 -350 mg/m2 / IV - day 1 ( every 21 days )
150 -180 mg/m2 / IV - day 1 ( every 14 days )
125 mg/m2 / IV - day 1 & 8 ( every 21 days )
4. Trifluridine and Tipiracil ( every 28 days )
35 mg / m2 up to a maximum dose of 80 mg per
dose ( based on trifluridine component )
PO twice daily on days 1-5 and 8-12

16. 5. Fluorouracil and irinotecan ( every 14 days )
➔ Irinotecan ( 180 mg/m2) / IV - day 1
➔ Leucovorin ( 400 mg/m2) / IV - day 1
➔ 5-FU (400 mg/m2) / IV - day 1
➔ 5-FU (1200 mg /m2 ) / IV continuous infusion over 24 hrs daily on
days 1 & 2
6. Pembrolizumab (every 21 days )
➔ 200 mg / IV on day 1

17. Immunotherapy as an adjuvant
● Based on the fact preoperative T-cell counts , percentage are reduced which can be
improved or modulated by this therapy
● Stage III carcinoma after radical gastrectomy
○ Started on pod- 5 till end of 2 years
● Regimen :
○ Picibanil ( streptococcus pyogenes derived )
■ Immune agent 1.0 clinical unit on 5th pod
■ From 10 th pod - Mitomycin C + 5-FU
■ Mitomycin C
● 4mg / 50 kg IV - twice weekly ( 2 weeks ) ------> weekly ( 6 weeks)
● 5 FU (500mg/kg ) - IV Twice weekly ( 2 weeks) -------> weekly ( 6
weeks) ---------> 600mg/kg orally daily for 2 years .

18. Immunotherapy
Pembrolizumab ( Keytruda )
★ MOA:
- Blocks PD-1 ( a protein on immune system called T-cells )
- Boost the immune response against cancer cells
- Shrink of tumours or slow down theri growth .
★ Used in patient , who already received treatment including chemotherapy
★ IV infusion , every 3 weeks

19. Radiotherapy
Preoperative and postoperative
➢ Diagnostic studies - identify tumour and pertinent nodal metastasis ( EUS ,
EGD,FDG-PET & CT )
Radiotherapy dosing
● 45- 50 Gy(1.8 Gy/d)
● Higher doses may be used for positive surgical margin in selected cases as a
boost to that area

20. ● External beam radiation therapy ----------> treat stomach cancer
○ 3D -CRT (conformal radiation therapy )
○ IMRT ( intensity modulated radiation therapy )
● Intraoperative radiation therapy
○ Ability to deliver more intensive of radiation to the tumour bed
○ Limited to stage III & IV disease
○ Dose 28-35 Gy
○ Limited data- about beneficial of IORT

21. Palliative care
Aim :
● Prevent and relieve suffering
● Best possible quality of life
● For gastric cancer - interventions undertaken to relieve major
symptoms may result in prolongation of life
Therefore , multimodality approach to palliative care of gastric cancer
patients is encouraged.

22. Karnofsky performance
score >60 % or ECOG score
- score < 2
Karnofsky performance
score <60 % or ECOG
score - score >3
Chemoradiation ( only if locally
unresectable & not previously
received )
(Or )systemic therapy
(or) best supportive therapy
Best supportive care

23. Bleeding
➢ Endoscopic treatment
○ Initially effective , rate of recurrent bleeding is very high
○ Injection therapy
○ Mechanical therapy -eg . endoscopic clips
○ Ablative therapy - eg. argon plasma coagulation
○ Combination methods
★ Interventional Radiology - Angiographic embolization technique
★ External beam radiation therapy - effectively manage acute and
chronic GI bleeding in multiple small series
★ Chronic blood loss from gastric cancer - PPI prescribed to reduce
bleeding risk from gastric cancer / external beam radiation therapy

24. Obstruction
Aim : reduce nausea , vomiting , if possible allow resumption of an oral diet
● Alleviate or bypass obstruction
○ Endoscopy - enteral stent placement -----> relief of outlet obstruction /
esophageal stent for EGJ/GOO
○ Surgery
■ Gastrojejunostomy
■ Gastrectomy in selected pts
○ External beam radiation therapy
○ Chemotherapy

25. ● Obstruction can’t be relieved or bypassed
○ Percutaneous , endoscopic , surgical or interventional radiology
gastrostomy tube placement
○ If ascites + -----> drained prior to venting gastrostomy
● Pts who can’t take oral diet
○ EGJ/gastric cardia obstruction -----> feeding gastrostomy
○ Mid and distal gastric obstruction ------ >feeding Jejunal tubes placement

26. Nausea and vomiting
● Luminal obstruction - endoscopic or fluoroscopic evaluation performed to
determine obstruction
Pain
● External beam radiation therapy
● Chemotherapy

27. References
1. .https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf
2. https://www.cancer.org/cancer/stomach-cancer/treating/targeted-therapies.html