The document discusses the role of chemotherapy in carcinoma of the stomach. It outlines several key trials investigating neoadjuvant, adjuvant and perioperative chemotherapy approaches. The MAGIC trial showed significantly improved 5-year survival with perioperative chemotherapy compared to surgery alone. The French FNCLCC trial also demonstrated improved disease-free and overall survival with perioperative chemotherapy. Adjuvant chemoradiation was shown in the INT0116/SWOG 9008 trial to improve 5-year overall and disease-free survival compared to surgery alone. The Japanese S-1 trial found significant benefit in 5-year disease-free and overall survival with adjuvant S-1 chemotherapy compared to observation after surgery.

1. ROLE OFCHEMOTHERAPYIN
CARCINOMA STOMACH
DR SAILENDRA
SENIOR RESIDENT
DEPT OF RADIOTHERAPY
MAULANA AZAD MEDICAL COLLEGE

2. STAGING

4. CURRENT RECOMMENDATION
• SURGERY ALONE
T1N0 and
selective T2N0
• SURGERY FOLLOWED BY CTRT
• PRE OP CT SX POST OP CT
T2-T4/
N+,RESECTABLE
• CTRT
• CHEMOTHERAPY ALONE
• BEST SUPPORTIVE CARE
UNRESECTABLE
• CHEMOTHERAPY ALONE
• BEST SUPPORTIVE CARE
• PALLIATIVE RT
M1

6. CHEMOTHERAPY
NEOADJUVANT
OR
PERIOPERATIVE
CONCURRENT
ADJUVANT

7. NEOADJUVANT/PERIOPERATIVE
3
TRIALS
MAGIC trial French
FNLCC/FFCD trial
EORTC trial 40954

8. MAGIC TRIAL

9. ELIGIBILITY CRITERIA
ANY AGE
STAGE T2 OR HIGHER
PS - 0 OR 1
ADENOCARCINOMA OF STOMACH OR DISTAL
ESOPHAGUS
NO EVIDENCE OF DISTANCE METASTASIS

10. 250
patients
Perioperative
chemotherapy
&
surgery
253
patients
Surgery only
TOTAL 503 PATIENTS
JULY 1994 TO APRIL 2002

11. CHEMOTHERAPY USED
Epirubicine Cisplatin
Infusional
5FU

12. PFS OS
5 yr survival 36% Vs 23%

13. SUMMARY
• PFS and OS are significantly better in
perioperative chemotherapy arm
• Estimated improvement in the five-year
survival rate was 13%.
• Local failure rate was 14% Vs 21%
• Distance metastasis rate was 24% Vs 37%

14. Limitations
• Nonstandardized surgery
• Inaccurate preoperative staging
• Higher proportion of patients in chemotherapy
arm undergo potentially curative surgery(79% VS
70%)
• T1/2 (52 Vs 37%)and N0/1(84 Vs 71%)patients are
more in chemotherapy arm
• Only 104 (42%) patients were able to complete
protocol treatment.

15. FRENCH FNCLCC TRIAL

16. THIS TRIAL WAS CLOSED EARLY DUE
TO LACK OF ACCRUAL
CHEMOTHERAPY USED WAS CISPLATIN AND 5FU
Between November, 1995,
and December, 2003

17. AFTER MEDIAN FOLLOW UP OF 5.7 YEARS
5YR DFS
34% VS 19%
5YR OS
38% VS 24%

18. SUMMARY
• Significant improvement in DFS and OS with
perioperative chemotherapy
• Most common toxicity were neutropenia and
nausea and vomiting.
• All the patients under go D2 resection which is
the standard surgical procedure in gastric
carcinoma.

19. LIMITATIONS
• Pretreatment staging was not reported.
• The planned sample size of the trial was not
reached.

20. META ANALYSIS
• Concluded that neoadjuvant chemotherapy was
associated with a statistically significant benefit in
terms of both overall survival and PFS.
• Neoadjuvant chemotherapy was associated with
a significantly higher complete (R0) tumor
resection rate and did not significantly worsen
rates of operative complications, perioperative
mortality, or grade 3 or 4 adverse effects.

21. ADJUVANT CHEMORADIATION
3
RANDOMIZED
TRIALS
INT0116/
SWOG
9008
(Macdonald
et al.)
CALGB
80101
ARTIST
TRIAL

23. patients with primaries T3 or higher
and/or node-positive gastric cancer
after R0 resection were randomised

24. RADIOCHEMOTHERAPY CONSISTED OF BOLUS
FLUOROURACIL AND LEUCOVORIN BEFORE,
DURING, AND AFTER RADIOTHERAPY.

25. STUDY DESIGN
1 MONTH AFTER RT
2 MORE CYCLES OF LVFU EVERY 28DAYS
FU 400 mg/m2/d and LV 20 mg/m2/d was given the
first four and the last three days of radiotherapy.
DAY 28
RADIOTHERAPY 45Gy/25# IN 5 WEEKS
DAY 1 TO 5
LEUCOVORIN(20mg) AND 5 FLUOROURACIL(425mg)

26. FIVE-YEAR OVERALL SURVIVAL 43% VERSUS
28% IN FAVOUR OF CTRT

27. 3 YEAR DISEASE FREE SURVIVAL 48% VS
31% IN FAVOUR OF CTRT

28. • DISTANT RELAPSE WAS 16% VS 18%
• REGIONAL RELAPSE WAS 22% VS 39%

29. SUMMARY
• Even after 10years of follow up the survival
advantage WITH CTRT is better than surgery
alone.
• 3yr OS was 50% Vs 41%
• 3yr RFS was 48% Vs 31%
• Toxicity was more with CTRT
• CTRT significantly decreases the locoregional
failure
• Standard of care in USA

30. LIMITATIONS
• D2 dissection was only performed in 10% of
cases.
• Only 64% of cases completed the treatment
and 17% discontinued treatment due to
toxicity

32. CALGB 80101: Study Schema
R
A
N
D
O
M
I
Z
E
5-FU/LV: 5-FU 425 mg/m2 d1-5, LV 20 mg/m2 d1-5
RT: 45 Gy (1.8 Gy X 25 fractions) with 5-FU 200 mg/m2/d CI
ECF (pre-RT): Epirubicin 50 mg/m2 d1, Cisplatin 60 mg/m2 d1, &
5-FU 200 mg/m2/d CI d1-21
ECF (post-RT): Epirubicin 40 mg/m2 d1, Cisplatin 50 mg/m2 d1, &
5-FU 200 mg/m2/d CI d1-21
5-FU/LV
X1
5-FU/LV
X2
5-FU IVCI
RT
ECF
X1
ECF
X2
5-FU IVCI
RT

33. NO DIFFERENCE
IN DFS
P=0.99
0 1 2 3 4 5 6 7
Years from Study Entry
0.00.20.40.60.81.0
ProportionSurvivingDisease-Free
ECF
5-FU
Disease_Free Survival by Arm
0 1 2 3 4 5 6 7
Years from Study Entry
0.00.20.40.60.81.0
ProportionSurviving
ECF
5-FU
Overall Survival by Arm
NO DIFFRENCE IN OS
P=0.80

34. ARTIST TRIAL

35. CAPECITABINE AND CISPLATIN 2 CYCLES
XPRT 45Gy IN 25#
CAPECITABINE AND CISPLATIN 6 CYCLESR
A
N
D
O
M
I
Z
E
D
458
patients
SURGERY
WITH D2 LN
DISSECTION
CAPECITABINE AND CISPLATIN 2 CYCLES

37. THERE WAS NO DIFFERENCE IN
DFS AND OS

38. SUMMARY
• No difference in DFS and OS
• Subset analysis indicate a significantly better
DFS with chemoradiotherapy in those with
node-positive disease (three-year DFS 76
versus 72 percent, p = 0.004).
• ARTIST –II TRIAL is going on that will further
address the advantage with adjuvant CTRT
over adjuvant chemotherapy.

39. META- ANALYSIS
A meta-analysis compared 6 trials of adjuvant
CTRT with chemotherapy and it conclude that
There is significantly improved 5 yr DFS and Local
control with CTRT
There is a trend towards improved overall survival
but that is not statistically significant

40. ADJUVANT CHEMOTHERAPY
2 TRIALS
JAPANESE
S-1 TRIAL
CLASSIC
trial

41. JAPANESE S-1 TRIAL
(ACTS GC)

42. • Stage II or III gastric cancer
• All had undergone potentially curative
surgery with D2 lymphadenectomy

43. Dose of S-1 was (80 to 120 mg daily for four
weeks, repeated every six weeks for one year)
S-1 is an oral fluoropyrimidine that includes
three different agents:
A. Tegafur
B. Gimeracil (5-chloro-2,4 dihydropyridine, a
potent inhibitor of DPD [dihydropyrimidine
dehydrogenase])
C. Oteracil (potassium oxonate, which inhibits
phosphorylation of intestinal FU, thought
responsible for treatment-related diarrhea)

44. RESULT
SIGNIFICANT BENEFIT IN 5YR DFS
AND OS IN S-1 ARM
P =0.003

45. • S-1 is approved in Japan for adjuvant therapy
of gastric cancer and in Europe for treatment
of advanced gastric cancer.
• It is not available in the United States.
• Except for anorexia (incidence, 6%), grade 3 or
4 adverse events occurred in less than 5% of
the patients in the S-1 group.

46. CLASSIC TRIAL

47. CLASSIC TRIAL DESIGN
CAPECITABINE AND OXALIPLATIN 8 CYCLESR
A
N
D
O
M
I
Z
E
D
1035
patients
SURGERY
WITH D2 LN
DISSECTION
NO ADJUVANT THERAPY
ATLEAST 15LN EXTRACTED
520 PATIENTS
515 PATIENTS

48. 3 YEAR DFS 74% VS 59%
P < 0.0001

49. 3 YEAR OS 83% VS 78%
P = 0.0493
5 YEAR OVERALL SURVIVAL IS 78% VS 69%

50. SUMMARY
• CAPECTABINE 1000mg/m2 DAY 1 -
14,OXALIPLATIN 130mg/m2 ON D1
• 9 TIMES MORE GRADE 3 & 4 TOXICITIES IN
CHEMOTHERAPY ARM
• ONLY 67% OF PATIENTS RECEIVED ALL 8
CYCLES OF CHEMOTHERAPY
• 90% OF PATIENTS REQUIRE CHEMOTHERAPY
DOSE MODIFICATION

51. ACCORDING TO NCCN
Chemotherapy prefered in
• PERIOPERATIVE REGIMEN IS
– Cisplatin and 5FU(cat-1) and ECF(cat-2)
• POST OPERATIVE REGIMEN
– CAPOX(IF RT CAN NOT BE GIVEN)
• CT BEFORE AND AFTER RT
– CAPECITABINE D-1 TO 14 OR LVFU