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Appendices

Appendix 1. CENTRAL update January 2013

1. exp stomach neoplasms/

2. (stomach adj5 neoplas$).ti,ab.

3. (stomach adj5 cancer$).ti,ab.

4. (stomach adj5 carcin$).ti,ab.

5. (stomach adj5 tumo$).ti,ab.

6. (stomach adj5 metasta$).ti,ab.

7. (stomach adj5 malig$).ti,ab.

8. (gastric adj5 neoplas$).ti,ab.

9. (gastric adj5 cancer$).ti,ab.

10. (gastric adj5 carcin$).ti,ab.

11. (gastric adj5 tumo$).ti,ab.

12. (gastric adj5 metasta$).ti,ab.

13. (gastric adj5 malig$).ti,ab.

14. or/1‐13

15. exp drug therapy/

16. chemothera$.ti,ab.

17. drug therap$.ti,ab.

18. antineoplastic$.ti,ab.

19. or/15‐18

20. exp palliative care/

21. palliat$.ti,ab.

22. unresect$.ti,ab.

23. inopera$.ti,ab.

24. advanc$.ti,ab.

25. (best adj5 support$ adj5 care).ti,ab.

26. unopera$.ti,ab.

27. (non adj5 resect$).ti,ab.

28. nonresect$.ti,ab.

29. or/20‐28

30. 14 and 19

31. 29 and 30

32. limit 31 to yr="2009 ‐ 2013"

Appendix 2. MEDLINE update March 2009‐Jan 2013

1. randomized controlled trial.pt.

2. controlled clinical trial.pt.

3. randomized.ab.

4. placebo.ab.

5. drug therapy.fs.

6. randomly.ab.

7. trial.ab.

8. groups.ab.

9. or/1‐8

10. exp animals/ not humans.sh.

11. 9 not 10

12. exp stomach neoplasms/

13. (stomach adj5 neoplas$).tw.

14. (stomach adj5 cancer$).tw.

15. (stomach adj5 carcin$).tw.

16. (stomach adj5 tumo$).tw.

17. (stomach adj5 metasta$).tw.

18. (stomach adj5 malig$).tw.

19. (gastric adj5 neoplas$).tw.

20. (gastric adj5 cancer$).tw.

21. (gastric adj5 carcin$).tw.

22. (gastric adj5 tumo$).tw.

23. (gastric adj5 metasta$).tw.

24. (gastric adj5 malig$).tw.

25. or/12‐24

26. exp drug therapy/

27. chemothera$.tw.

28. drug therap$.tw.

29. antineoplastic$.tw.

30. or/26‐29

31. exp palliative care/

32. palliat$.tw.

33. unresect$.tw.

34. inopera$.tw.

35. advanc$.tw.

36. (best adj5 support$ adj5 care).tw.

37. unopera$.tw.

38. (non adj5 resect$).tw.

39. nonresect$.tw.

40. or/31‐39

41. 25 and 30

42. 40 and 41

43. 42 and 11

44. limit 43 to ed=20090309‐20130131

Appendix 3. Embase update March 2009‐Jan 2013

1. exp randomized controlled trial/

2. randomi?ed controlled trial$.tw.

3. exp randomization/

4. exp single blind procedure/

5. exp double blind procedure/

6. or/1‐5

7. animal.hw.

8. human.hw.

9. 7 not (7 and 8)

10. 6 not 9

11. exp clinical trial/

12. (clin$ adj3 stud$).ti,ab,tw.

13. (clin$ adj3 trial$).ti,ab,tw.

14. ((singl$ or doubl$ or treb$ or tripl$) adj3 (blind$ or mask$)).ti,ab,tw.

15. exp placebo/

16. placebo$.ti,ab,tw.

17. random.ti,ab,tw.

18. (crossover$ or cross‐over$).ti,ab,tw.

19. or/11‐18

20. 19 not 9

21. 20 not 10

22. exp comparative study/

23. exp evaluation/

24. exp prospective study/

25. exp controlled study/

26. (control$ or prospective$ or volunteer$).ti,ab,tw.

27. or/22‐26

28. 27 not 9

29. 10 or 21 or 28

30. exp stomach tumor/

31. (stomach adj5 neoplas$).tw.

32. (stomach adj5 cancer$).tw.

33. (stomach adj5 carcin$).tw.

34. (stomach adj5 tumo$).tw.

35. (stomach adj5 metasta$).tw.

36. (stomach adj5 malig$).tw.

37. (gastric adj5 neoplas$).tw.

38. (gastric adj5 cancer$).tw.

39. (gastric adj5 carcin$).tw.

40. (gastric adj5 tumo$).tw.

41. (gastric adj5 metasta$).tw.

42. (gastric adj5 malig$).tw.

43. or/30‐42

44. exp drug therapy/

45. chemothera$.tw.

46. drug therap$.tw.

47. antineoplastic$.tw.

48. or/44‐47

49. exp palliative therapy/

50. palliat$.tw.

51. unresect$.tw.

52. inopera$.tw.

53. advanc$.tw.

54. (best adj5 support$ adj5 care).tw.

55. unopera$.tw.

56. (non adj5 resect$).tw.

57. nonresect$.tw.

58. or/49‐57

59. 43 and 48

60. 58 and 59

61. 29 and 60

62. limit 61 to em=200910‐201306

Study flow diagram: review update
Figuras y tablas -
Figure 1

Study flow diagram: review update

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 2

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 3

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Comparison 1 Chemotherapy versus best supportive care, Outcome 1 Overall survival.
Figuras y tablas -
Analysis 1.1

Comparison 1 Chemotherapy versus best supportive care, Outcome 1 Overall survival.

Comparison 1 Chemotherapy versus best supportive care, Outcome 2 Time to progression.
Figuras y tablas -
Analysis 1.2

Comparison 1 Chemotherapy versus best supportive care, Outcome 2 Time to progression.

Comparison 2 Combination versus single‐agent chemotherapy, Outcome 1 Overall survival.
Figuras y tablas -
Analysis 2.1

Comparison 2 Combination versus single‐agent chemotherapy, Outcome 1 Overall survival.

Comparison 2 Combination versus single‐agent chemotherapy, Outcome 2 Tumour response.
Figuras y tablas -
Analysis 2.2

Comparison 2 Combination versus single‐agent chemotherapy, Outcome 2 Tumour response.

Comparison 2 Combination versus single‐agent chemotherapy, Outcome 3 Time to progression.
Figuras y tablas -
Analysis 2.3

Comparison 2 Combination versus single‐agent chemotherapy, Outcome 3 Time to progression.

Comparison 2 Combination versus single‐agent chemotherapy, Outcome 4 Treatment‐related death.
Figuras y tablas -
Analysis 2.4

Comparison 2 Combination versus single‐agent chemotherapy, Outcome 4 Treatment‐related death.

Comparison 3 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/cisplatin combinations (without anthracyclines), Outcome 1 Overall survival.
Figuras y tablas -
Analysis 3.1

Comparison 3 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/cisplatin combinations (without anthracyclines), Outcome 1 Overall survival.

Comparison 3 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/cisplatin combinations (without anthracyclines), Outcome 2 Tumour response.
Figuras y tablas -
Analysis 3.2

Comparison 3 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/cisplatin combinations (without anthracyclines), Outcome 2 Tumour response.

Comparison 3 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/cisplatin combinations (without anthracyclines), Outcome 3 Time to progression.
Figuras y tablas -
Analysis 3.3

Comparison 3 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/cisplatin combinations (without anthracyclines), Outcome 3 Time to progression.

Comparison 4 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/anthracycline combinations (without cisplatin), Outcome 1 Overall survival.
Figuras y tablas -
Analysis 4.1

Comparison 4 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/anthracycline combinations (without cisplatin), Outcome 1 Overall survival.

Comparison 5 Chemotherapy with irinotecan versus non‐irinotecan‐containing regimes, Outcome 1 Overall survival.
Figuras y tablas -
Analysis 5.1

Comparison 5 Chemotherapy with irinotecan versus non‐irinotecan‐containing regimes, Outcome 1 Overall survival.

Comparison 5 Chemotherapy with irinotecan versus non‐irinotecan‐containing regimes, Outcome 2 Tumour response.
Figuras y tablas -
Analysis 5.2

Comparison 5 Chemotherapy with irinotecan versus non‐irinotecan‐containing regimes, Outcome 2 Tumour response.

Comparison 5 Chemotherapy with irinotecan versus non‐irinotecan‐containing regimes, Outcome 3 Progression‐free survival.
Figuras y tablas -
Analysis 5.3

Comparison 5 Chemotherapy with irinotecan versus non‐irinotecan‐containing regimes, Outcome 3 Progression‐free survival.

Comparison 5 Chemotherapy with irinotecan versus non‐irinotecan‐containing regimes, Outcome 4 Treatment‐related death.
Figuras y tablas -
Analysis 5.4

Comparison 5 Chemotherapy with irinotecan versus non‐irinotecan‐containing regimes, Outcome 4 Treatment‐related death.

Comparison 5 Chemotherapy with irinotecan versus non‐irinotecan‐containing regimes, Outcome 5 Treatment discontinuation due to toxicity.
Figuras y tablas -
Analysis 5.5

Comparison 5 Chemotherapy with irinotecan versus non‐irinotecan‐containing regimes, Outcome 5 Treatment discontinuation due to toxicity.

Comparison 6 Chemotherapy with docetaxel versus non‐docetaxel‐containing regimes, Outcome 1 Overall survival.
Figuras y tablas -
Analysis 6.1

Comparison 6 Chemotherapy with docetaxel versus non‐docetaxel‐containing regimes, Outcome 1 Overall survival.

Comparison 6 Chemotherapy with docetaxel versus non‐docetaxel‐containing regimes, Outcome 2 Tumour response.
Figuras y tablas -
Analysis 6.2

Comparison 6 Chemotherapy with docetaxel versus non‐docetaxel‐containing regimes, Outcome 2 Tumour response.

Comparison 6 Chemotherapy with docetaxel versus non‐docetaxel‐containing regimes, Outcome 3 Time to progression.
Figuras y tablas -
Analysis 6.3

Comparison 6 Chemotherapy with docetaxel versus non‐docetaxel‐containing regimes, Outcome 3 Time to progression.

Comparison 6 Chemotherapy with docetaxel versus non‐docetaxel‐containing regimes, Outcome 4 Progression‐free survival.
Figuras y tablas -
Analysis 6.4

Comparison 6 Chemotherapy with docetaxel versus non‐docetaxel‐containing regimes, Outcome 4 Progression‐free survival.

Comparison 6 Chemotherapy with docetaxel versus non‐docetaxel‐containing regimes, Outcome 5 Treatment‐related death.
Figuras y tablas -
Analysis 6.5

Comparison 6 Chemotherapy with docetaxel versus non‐docetaxel‐containing regimes, Outcome 5 Treatment‐related death.

Comparison 6 Chemotherapy with docetaxel versus non‐docetaxel‐containing regimes, Outcome 6 Treatment discontinuation due to toxicity.
Figuras y tablas -
Analysis 6.6

Comparison 6 Chemotherapy with docetaxel versus non‐docetaxel‐containing regimes, Outcome 6 Treatment discontinuation due to toxicity.

Comparison 7 Chemotherapy with capecitabine versus 5‐FU‐containing regimes, Outcome 1 Overall Survival.
Figuras y tablas -
Analysis 7.1

Comparison 7 Chemotherapy with capecitabine versus 5‐FU‐containing regimes, Outcome 1 Overall Survival.

Comparison 7 Chemotherapy with capecitabine versus 5‐FU‐containing regimes, Outcome 2 Tumour response.
Figuras y tablas -
Analysis 7.2

Comparison 7 Chemotherapy with capecitabine versus 5‐FU‐containing regimes, Outcome 2 Tumour response.

Comparison 7 Chemotherapy with capecitabine versus 5‐FU‐containing regimes, Outcome 3 Time to progression.
Figuras y tablas -
Analysis 7.3

Comparison 7 Chemotherapy with capecitabine versus 5‐FU‐containing regimes, Outcome 3 Time to progression.

Comparison 7 Chemotherapy with capecitabine versus 5‐FU‐containing regimes, Outcome 4 Progression‐free survival.
Figuras y tablas -
Analysis 7.4

Comparison 7 Chemotherapy with capecitabine versus 5‐FU‐containing regimes, Outcome 4 Progression‐free survival.

Comparison 7 Chemotherapy with capecitabine versus 5‐FU‐containing regimes, Outcome 5 Treatment‐related death.
Figuras y tablas -
Analysis 7.5

Comparison 7 Chemotherapy with capecitabine versus 5‐FU‐containing regimes, Outcome 5 Treatment‐related death.

Comparison 7 Chemotherapy with capecitabine versus 5‐FU‐containing regimes, Outcome 6 Treatment discontinuation due to toxicity.
Figuras y tablas -
Analysis 7.6

Comparison 7 Chemotherapy with capecitabine versus 5‐FU‐containing regimes, Outcome 6 Treatment discontinuation due to toxicity.

Comparison 8 Chemotherapy with oxaliplatin versus the same regime including cisplatin, Outcome 1 Overall Survival.
Figuras y tablas -
Analysis 8.1

Comparison 8 Chemotherapy with oxaliplatin versus the same regime including cisplatin, Outcome 1 Overall Survival.

Comparison 8 Chemotherapy with oxaliplatin versus the same regime including cisplatin, Outcome 2 Tumour response.
Figuras y tablas -
Analysis 8.2

Comparison 8 Chemotherapy with oxaliplatin versus the same regime including cisplatin, Outcome 2 Tumour response.

Comparison 8 Chemotherapy with oxaliplatin versus the same regime including cisplatin, Outcome 3 Progression‐free survival.
Figuras y tablas -
Analysis 8.3

Comparison 8 Chemotherapy with oxaliplatin versus the same regime including cisplatin, Outcome 3 Progression‐free survival.

Comparison 8 Chemotherapy with oxaliplatin versus the same regime including cisplatin, Outcome 4 Treatment‐related death.
Figuras y tablas -
Analysis 8.4

Comparison 8 Chemotherapy with oxaliplatin versus the same regime including cisplatin, Outcome 4 Treatment‐related death.

Comparison 8 Chemotherapy with oxaliplatin versus the same regime including cisplatin, Outcome 5 Treatment discontinuation due to toxicity.
Figuras y tablas -
Analysis 8.5

Comparison 8 Chemotherapy with oxaliplatin versus the same regime including cisplatin, Outcome 5 Treatment discontinuation due to toxicity.

Comparison 9 Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine), Outcome 1 Overall survival.
Figuras y tablas -
Analysis 9.1

Comparison 9 Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine), Outcome 1 Overall survival.

Comparison 9 Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine), Outcome 2 Tumour response.
Figuras y tablas -
Analysis 9.2

Comparison 9 Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine), Outcome 2 Tumour response.

Comparison 9 Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine), Outcome 3 Progression‐free survival.
Figuras y tablas -
Analysis 9.3

Comparison 9 Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine), Outcome 3 Progression‐free survival.

Comparison 9 Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine), Outcome 4 Treatment‐related death.
Figuras y tablas -
Analysis 9.4

Comparison 9 Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine), Outcome 4 Treatment‐related death.

Comparison 9 Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine), Outcome 5 Treatment discontinuation due to toxicity.
Figuras y tablas -
Analysis 9.5

Comparison 9 Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine), Outcome 5 Treatment discontinuation due to toxicity.

Comparison 10 S‐1 versus 5‐FU‐containing regimes, Outcome 1 Overall Survival.
Figuras y tablas -
Analysis 10.1

Comparison 10 S‐1 versus 5‐FU‐containing regimes, Outcome 1 Overall Survival.

Comparison 10 S‐1 versus 5‐FU‐containing regimes, Outcome 2 Tumour response.
Figuras y tablas -
Analysis 10.2

Comparison 10 S‐1 versus 5‐FU‐containing regimes, Outcome 2 Tumour response.

Comparison 10 S‐1 versus 5‐FU‐containing regimes, Outcome 3 Progression‐free survival.
Figuras y tablas -
Analysis 10.3

Comparison 10 S‐1 versus 5‐FU‐containing regimes, Outcome 3 Progression‐free survival.

Comparison 10 S‐1 versus 5‐FU‐containing regimes, Outcome 4 Time‐to treatment failure.
Figuras y tablas -
Analysis 10.4

Comparison 10 S‐1 versus 5‐FU‐containing regimes, Outcome 4 Time‐to treatment failure.

Comparison 10 S‐1 versus 5‐FU‐containing regimes, Outcome 5 Treatment‐related deaths.
Figuras y tablas -
Analysis 10.5

Comparison 10 S‐1 versus 5‐FU‐containing regimes, Outcome 5 Treatment‐related deaths.

Comparison 10 S‐1 versus 5‐FU‐containing regimes, Outcome 6 Treatment discontinuation due to toxicity.
Figuras y tablas -
Analysis 10.6

Comparison 10 S‐1 versus 5‐FU‐containing regimes, Outcome 6 Treatment discontinuation due to toxicity.

Summary of findings for the main comparison. Chemotherapy versus best supportive care for advanced gastric cancer

Chemotherapy versus best supportive care for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies
Intervention: chemotherapy

Control: best supportive care alone

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Best supportive care

Chemotherapy

Overall survival

Study population

HR 0.37
(0.24 to 0.55)

184
(3 studies)

⊕⊕⊕⊝
moderate1

Weighted average of median survival durations from included studies

4.3 months

11.0 months

Time to progression

Study population

HR 0.31
(0.22 to 0.43)

144
(2 studies)

⊕⊕⊕⊝
moderate1

Weighted average of median survival durations from included studies

2.5 months

7.4 months

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Early termination of Pyrhönen 1995; downgraded by one level for risk of bias.

Outcomes shown include those which were measured in the studies, or reported in a consistent fashion across included studies. Several critical outcomes (e.g. tumour response, treatment‐related death, and discontinuation due to toxicity) were not evaluated or reported in a consistent fashion in these studies, as they were mainly conducted before year 2000.

Figuras y tablas -
Summary of findings for the main comparison. Chemotherapy versus best supportive care for advanced gastric cancer
Summary of findings 2. Combination versus single‐agent chemotherapy for advanced gastric cancer

Combination versus single‐agent chemotherapy for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies
Intervention: combination

Control: single‐agent chemotherapy

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Single‐agent chemotherapy

Combination

Overall survival

Study population

HR 0.84
(0.79 to 0.89)

4447
(23)

⊕⊕⊕⊝
moderate1

Weighted average of median survival durations from included studies

  • 10.5 months in studies published after year 2000

  • 6.4 months in studies published before year 2000

  • 11.6 months in studies published after year 2000

  • 7.3 months in studies published before year 2000

Tumour response

Study population

OR 2.30
(1.94 to 2.72)

2833
(18)

⊕⊕⊕⊕
high1

226 per 1000

402 per 1000
(361 to 442)

Moderate

231 per 1000

409 per 1000
(368 to 450)

Time to progression

Study population

HR 0.69
(0.55 to 0.87)

720
(4)

⊕⊕⊕⊝
moderate1

Weighted average of median survival durations from included studies

2.8 months

4.1 months

Treatment‐related death

Study population

OR 1.64
(0.83 to 3.24)

3876
(18)

⊕⊕⊝⊝
moderate2

5 per 1000

9 per 1000
(4 to 17)

Moderate

0 per 1000

0 per 1000
(0 to 0)

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded by one level for risk of bias.
2 Downgraded by two levels for serious imprecision.

Figuras y tablas -
Summary of findings 2. Combination versus single‐agent chemotherapy for advanced gastric cancer
Summary of findings 3. 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/cisplatin combinations (without anthracyclines) for advanced gastric cancer

5‐FU/cisplatin/anthracycline combinations versus 5‐FU/cisplatin combinations (without anthracyclines) for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies
Intervention: 5‐FU/cisplatin/anthracycline combinations

Control: 5‐FU/cisplatin combinations (without anthracyclines)

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

5‐FU/cisplatin combinations (without anthracyclines)

5‐FU/cisplatin/anthracycline combinations

Overall survival

Study population

HR 0.74
(0.61 to 0.89)

579
(4)

⊕⊕⊕⊝
moderate1

Weighted average of median survival durations from included studies

8.6 months

9.9 months

Tumour response

Study population

OR 2.86
(1.14 to 7.16)

78
(1)

⊕⊕⊝⊝
low2

385 per 1000

641 per 1000
(416 to 817)

Moderate

385 per 1000

642 per 1000
(416 to 818)

Time to progression

Study population

HR 0.62
(0.38 to 0.98)

78
(1)

⊕⊕⊝⊝
low2

Median survival durations from the only included study

7.9 months

12.1 months

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded by one level for risk of bias.
2 Downgraded by two levels for serious imprecision.

Outcomes shown include those which were measured in the studies, or reported in a consistent fashion across included studies. Several critical outcomes (e.g. treatment‐related death and discontinuation due to toxicity) were not evaluated or reported in a consistent fashion in these studies, as they were mainly conducted before year 2000.

Figuras y tablas -
Summary of findings 3. 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/cisplatin combinations (without anthracyclines) for advanced gastric cancer
Summary of findings 4. 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/anthracycline combinations (without cisplatin) for advanced gastric cancer

5‐FU/cisplatin/anthracycline combinations versus 5‐FU/anthracycline combinations (without cisplatin) for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies
Intervention: 5‐FU/cisplatin/anthracycline combinations

Control: 5‐FU/cisplatin combinations (without anthracyclines)

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

5‐FU/anthracycline combinations (without cisplatin)

5‐FU/cisplatin/anthracycline combinations

Overall survival

Study population

HR 0.82
(0.73 to 0.92)

1147
(7)

⊕⊕⊝⊝
low1,2

Weighted average of median survival durations from included studies

6.2 months

8.4 months

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded by one level for risk of bias.
2 Downgraded by one level for statistical heterogeneity.

Several critical outcomes (i.e. tumour response, progression‐free survival, treatment‐related death and discontinuation due to toxicity) were not evaluated or reported in a consistent fashion in these studies, most of which were conducted before year 2000.

Figuras y tablas -
Summary of findings 4. 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/anthracycline combinations (without cisplatin) for advanced gastric cancer
Summary of findings 5. Irinotecan versus non‐irinotecan‐containing regimens for advanced gastric cancer

Irinotecan versus non‐irinotecan‐containing regimens for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies
Intervention: irinotecan

Control: non‐irinotecan‐containing regimens

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Non‐irinotecan‐containing regimens

Chemotherapy with Irinotecan

Overall survival

Study population

HR 0.87
(0.80 to 0.95)

2135
(10 studies)

⊕⊕⊕⊝
moderate1

Weighted average of median survival durations from included studies

9.7 months

11.3 months

Overall survival ‐ Substitutive comparisons

Study population

HR 0.87

(0.75 to 1.00)

826
(6 studies)

⊕⊕⊕⊝
moderate1

Weighted average of median survival durations from included studies

9.1 months

9.9 months

Overall survival ‐ Additive comparisons

Study population

HR 0.88
(0.76 to 1.03)

500
(3 studies)

⊕⊕⊝⊝
low1,2

Weighted average of median survival durations from included studies

10.9 months

11.9 months

Overall survival ‐ Other comparisons

Study population

HR 0.87
(0.76 to 1.00)

809
(2 studies)

⊕⊝⊝⊝
very low1,3

Weighted average of median survival durations from included studies

11.4 months

12.6 months

Tumour response

Study population

OR 1.72

(1.24 to 2.40)

1266
(10 studies)

⊕⊕⊝⊝
low3

288 per 1000

410 per 1000
(334 to 493)

Moderate

275 per 1000

395 per 1000
(320 to 477)

Tumour response ‐ Substitutive comparisons

Study population

OR 1.53

(0.93 to 2.50)

756
(6 studies)

⊕⊕⊝⊝
low3

297 per 1000

393 per 1000
(282 to 514)

Moderate

294 per 1000

389 per 1000
(279 to 510)

Tumour response ‐ Additive comparisons

Study population

OR 2.18

(1.25 to 3.80)

345
(3 studies)

⊕⊕⊝⊝
low1,2

224 per 1000

386 per 1000
(265 to 522)

Moderate

219 per 1000

379 per 1000
(260 to 516)

Tumour response ‐ Other comparisons

Study population

OR 1.87
(0.89 to 3.91)

165
(2 studies)

⊕⊝⊝⊝
very low1,2,4

376 per 1000

530 per 1000
(350 to 702)

Moderate

367 per 1000

520 per 1000
(340 to 694)

Progression‐free survival

Study population

HR 0.76

(0.69 to 0.84)

1640
(7 studies)

⊕⊕⊕⊕
high

Weighted average of median survival durations from included studies

4.4 months

5.9 months

Progression‐free survival ‐ Substitutive comparison

Study population

HR 0.85

(0.72 to 1.00)

741
(5 studies)

⊕⊕⊕⊝
moderate1

Weighted average of median survival durations from included studies

4.2 months

5.3 months

Progression‐free survival ‐ Additive comparisons

Study population

HR 0.51
(0.33 to 0.77)

90
(1)

⊕⊕⊕⊝
moderate2

Median survival durations from the only included study

3.2 months

6.9 months

Progression‐free survival ‐ Other comparisons

Study population

HR 0.74

(0.66 to 0.84)

809
(2 studies)

⊕⊕⊕⊕
high

Weighted average of median survival durations from included studies

5.4 months

6.6 months

Treatment‐related death

Study population

OR 0.88

(0.23 to 3.32)

1979
(9 studies)

⊕⊕⊝⊝
low2,4

10 per 1000

9 per 1000
(2 to 32)

Moderate

2 per 1000

2 per 1000
(0 to 7)

Treatment discontinuation due to toxicity

Study population

OR 1.00

(0.46 to 2.20)

1979
(9 studies)

⊕⊝⊝⊝
very low2,3

137 per 1000

137 per 1000
(68 to 258)

Moderate

215 per 1000

215 per 1000
(112 to 376)

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded by one level for risk of bias.
2 Downgraded by one level for imprecision.
3 Downgraded by two levels for severe statistical heterogeneity.
4 Downgraded by one level for statistical heterogeneity.

Figuras y tablas -
Summary of findings 5. Irinotecan versus non‐irinotecan‐containing regimens for advanced gastric cancer
Summary of findings 6. Docetaxel versus non‐docetaxel‐containing regimens for advanced gastric cancer

Docetaxel versus non‐docetaxel‐containing regimens for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies
Intervention: docetaxel

Control: non‐docetaxel‐containing regimens

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Non‐docetaxel‐containing regimens

Chemotherapy with docetaxel

Overall survival

Study population

HR 0.86

(0.78 to 0.95)

2001
(8 studies)

⊕⊕⊕⊕
high

Weighted average of median survival durations from included studies

9.9 months

11.2 months

Overall survival ‐ Substitutive comparisons

Study population

HR 1.05

(0.87 to 1.27)

479
(3 studies)

⊕⊕⊕⊝
moderate1

Weighted average of median survival durations from included studies

9.4 months

9.2 months

Overall survival ‐ Additive comparisons

Study population

HR 0.80

(0.71 to 0.91)

1466
(4 studies)

⊕⊕⊕⊝
moderate2

Weighted average of median survival durations from included studies

10.6 months

12.3 months

Overall survival ‐ Other comparisons

Study population

HR 0.80

(0.46 to 1.39)

56
(1 study)

⊕⊝⊝⊝
very low1,2,3

Median survival durations from the only included study

9.5 months

11.9 months

Tumour response

Study population

OR 1.37

(1.03 to 1.83)

1820
(9 studies)

⊕⊕⊕⊝
moderate4

311 per 1000

382 per 1000
(317 to 452)

Moderate

310 per 1000

381 per 1000
(316 to 451)

Tumour response ‐ Substitutive comparison

Study population

OR 1.03

(0.71 to 1.50)

525
(4 studies)

⊕⊕⊕⊝
moderate1

314 per 1000

320 per 1000
(245 to 407)

Moderate

327 per 1000

334 per 1000
(256 to 422)

Tumour response ‐ Additive comparison

Study population

OR 1.83

(1.45 to 2.32)

1235
(4 studies)

⊕⊕⊕⊕
high

295 per 1000

434 per 1000
(378 to 493)

Moderate

296 per 1000

435 per 1000
(379 to 494)

Tumour response ‐ Other comparison

Study population

OR 0.33

(0.12 to 0.96)

60
(1 study)

⊕⊝⊝⊝
very low1,3

600 per 1000

331 per 1000
(153 to 590)

Moderate

600 per 1000

331 per 1000
(153 to 590)

Time to progression

Study population

HR 1.06

(0.85 to 1.32)

360
(2 studies)

⊕⊝⊝⊝
very low1,2,3

Weighted average of median survival durations from included studies

6.0 months

5.9 months

Progression‐free survival

Study population

HR 0.76

(0.63 to 0.91)

1498
(5 studies)

⊕⊕⊕⊝
moderate4

Weighted average of median survival durations from included studies

4.8 months

6.0 months

Progression‐free survival ‐ Substitutive comparisons

Study population

HR 1.15

(0.77 to 1.72)

119
(1 study)

⊕⊝⊝⊝
very low1,2,3

Median survival durations from the only included study

4.9 months

4.6 months

Progression‐free survival ‐ Additive comparison

Study population

HR 0.70

(0.61 to 0.81)

1323
(3 studies)

⊕⊕⊕⊕
high

Weighted average of median survival durations from included studies

4.3 months

6.0 months

Progression‐free survival ‐ Other comparison

Study population

HR 0.94

(0.55 to 1.60)

56
(1 study)

⊕⊝⊝⊝
very low1,3

Median survival durations from the only included study

6.4 months

6.8 months

Treatment‐related death

Study population

OR 1.10
(0.55 to 2.20)

2113
(7 studies)

⊕⊕⊕⊝
moderate1

12 per 1000

14 per 1000
(7 to 27)

Moderate

5 per 1000

5 per 1000
(3 to 11)

Treatment discontinuation due to toxicity

Study population

OR 0.81

(0.53 to 1.25)

1066
(5 studies)

⊕⊕⊝⊝
low1,4

211 per 1000

178 per 1000
(124 to 251)

Moderate

197 per 1000

166 per 1000
(115 to 235)

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded by one level for imprecision.
2 Downgraded by one level for risk of bias.
3 Downgraded by two levels for serious imprecision.
4 Downgraded by one level for statistical heterogeneity.

Figuras y tablas -
Summary of findings 6. Docetaxel versus non‐docetaxel‐containing regimens for advanced gastric cancer
Summary of findings 7. Capecitabine versus 5‐FU‐containing regimens for advanced gastric cancer

Capecitabine versus 5‐FU‐containing regimens for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies with approximately half of all participants enrolled from Asian countries
Intervention: capecitabine

Control: 5‐FU‐containing regimens

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

5‐FU‐containing regimens

Capecitabine‐containing regimens

Overall Survival

Study population

HR 0.94

(0.79 to 1.11)

732
(5 studies)

⊕⊕⊕⊝
moderate1

Weighted average of median survival durations from included studies

10.9 months

10.8 months

Tumour response

Study population

OR 0.85

(0.40 to 1.79)

636
(4 studies)

⊕⊝⊝⊝
very low2,3

384 per 1000

347 per 1000
(200 to 528)

Moderate

394 per 1000

356 per 1000
(206 to 538)

Time to progression

Study population

HR 0.72

(0.47 to 1.12)

85
(1 study)

⊕⊝⊝⊝
very low1,3

Median survival durations from the only included study

5.5 months

6.8 months

Progression‐free survival

Study population

HR 0.98

(0.77 to 1.23)

647
(4 studies)

⊕⊝⊝⊝
very low1,3,4

Weighted average of median survival durations from included studies

6.7 months

6.5 months

Treatment‐related death

Study population

OR 1.88

(0.23 to 15.15)

481
(2 studies)

⊕⊝⊝⊝
very low1,2,3

21 per 1000

38 per 1000
(5 to 241)

Moderate

24 per 1000

44 per 1000
(6 to 271)

Treatment discontinuation due to toxicity

Study population

OR 0.99

(0.56 to 1.77)

311
(1 study)

⊕⊕⊝⊝
low3

181 per 1000

179 per 1000
(110 to 281)

Moderate

181 per 1000

180 per 1000
(110 to 281)

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded by one level for risk of bias.
2 Downgraded by two levels for severe statistical heterogeneity.
3 Downgraded by two levels for serious imprecision.
4 Downgraded by one level for statistical heterogeneity.

Figuras y tablas -
Summary of findings 7. Capecitabine versus 5‐FU‐containing regimens for advanced gastric cancer
Summary of findings 8. Oxaliplatin versus the same regimen including cisplatin for advanced gastric cancer

Oxaliplatin versus the same regimen including cisplatin for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies with the majority of participants enrolled in Asia
Intervention: oxaliplatin‐containing regimen

Control: the same regimen including cisplatin

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Cisplatin‐containing regimen

Oxaliplatin‐containing regimen

Overall Survival

Study population

HR 0.81

(0.67 to 0.98)

1105
(5 studies)

⊕⊕⊝⊝
low1,2

Weighted average of median survival durations from included studies

11.3 months

14.0 months

Tumour response

Study population

OR 1.38

(1.08 to 1.76)

1081
(5 studies)

⊕⊕⊕⊝
moderate1

468 per 1000

548 per 1000
(487 to 607)

Moderate

458 per 1000

538 per 1000
(477 to 598)

Progression‐free survival

Study population

HR 0.88

(0.66 to 1.19)

1034
(4 studies)

⊕⊕⊝⊝
low1,3

Weighted average of median survival durations from included studies

4.9 months

6.0 months

Treatment‐related death

Study population

OR 0.47

(0.17 to 1.30)

1132
(5 studies)

⊕⊕⊝⊝
low1,3

20 per 1000

9 per 1000
(3 to 25)

Moderate

24 per 1000

11 per 1000
(4 to 31)

Treatment discontinuation due to toxicity

Study population

OR 0.97

(0.44 to 2.13)

970
(3 studies)

⊕⊝⊝⊝
very low1,2,3

95 per 1000

93 per 1000
(44 to 183)

Moderate

102 per 1000

99 per 1000
(48 to 195)

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded by one level for risk of bias.
2 Downgraded by one level for statistical heterogeneity.
3 Downgraded by one level for imprecision.

Figuras y tablas -
Summary of findings 8. Oxaliplatin versus the same regimen including cisplatin for advanced gastric cancer
Summary of findings 9. Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine) for advanced gastric cancer

Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine) for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies, without Asian representation
Intervention: taxane‐platinum‐fluoropyrimidine combinations

Control: taxane‐platinum (without fluoropyrimidine)

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Taxane‐platinum (without fluoropyrimidine)

Taxane‐platinum‐fluoropyrimidine combination

Overall survival

Study population

OR 0.86
(0.71 to 1.06)

482
(3 studies)

⊕⊝⊝⊝
very low1,2

Weighted average of median survival durations from included studies

10.0 months

11.7 months

Tumour response

Study population

OR 2.08
(1.37 to 3.15)

482
(3 studies)

⊕⊕⊝⊝
low1,3

234 per 1000

389 per 1000
(295 to 491)

Moderate

231 per 1000

385 per 1000
(292 to 486)

Progression‐free survival

Study population

OR 0.74
(0.59 to 0.93)

482
(3 studies)

⊕⊕⊕⊝
moderate1

Weighted average of median survival durations from included studies

4.4 months

5.7 months

Treatment‐related death

Study population

OR 1.95
(0.73 to 5.17)

482
(3 studies)

⊕⊝⊝⊝
very low1,4

26 per 1000

50 per 1000
(19 to 121)

Moderate

13 per 1000

25 per 1000
(10 to 64)

Treatment discontinuation due to toxicity

Study population

OR 1.71
(0.79 to 3.69)

234
(2 studies)

⊕⊝⊝⊝
very low1,4

105 per 1000

167 per 1000
(85 to 303)

Moderate

99 per 1000

158 per 1000
(80 to 288)

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded by one level for risk of bias.
2 Downgraded by two levels for severe statistical heterogeneity.
3 Downgraded by one level for imprecision.
4 Downgraded by two levels for serious imprecision.

Figuras y tablas -
Summary of findings 9. Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine) for advanced gastric cancer
Summary of findings 10. S‐1 versus 5‐FU‐containing regimens for advanced gastric cancer

S‐1 versus 5‐FU‐containing regimens for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies, mostly performed in Asia
Intervention: S‐1‐containing regimens

Control: 5‐FU‐containing regimens

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

5‐FU‐containing regimens

S‐1 containing regimens

Overall Survival

Study population

HR 0.91
(0.83 to 1.00)

1793
(4 studies)

⊕⊕⊕⊕
high

Weighted average of median survival durations from included studies

9.1 months

9.6 months

Tumour response

Study population

OR 1.73
(1.01 to 2.94)

1753
(7 studies)

⊕⊝⊝⊝
very low1,2

256 per 1000

374 per 1000
(258 to 503)

Moderate

320 per 1000

449 per 1000
(322 to 580)

Progression‐free survival

Study population

HR 0.85
(0.70 to 1.04)

1942
(4 studies)

⊕⊕⊝⊝
low1

Weighted average of median survival durations from included studies

4.3 months

5.0 months

Time‐to treatment failure

Study population

HR 0.88
(0.76 to 1.01)

1818
(5 studies)

⊕⊕⊝⊝
low1

Weighted average of median survival durations from included studies

3.1 months

3.9 months

Treatment‐related deaths

Study population

OR 0.56
(0.30 to 1.06)

1962
(4 studies)

⊕⊕⊕⊝
moderate2

27 per 1000

15 per 1000
(8 to 28)

Moderate

5 per 1000

3 per 1000
(2 to 5)

Treatment discontinuation due to toxicity

Study population

OR 0.85
(0.63 to 1.13)

1726
(3 studies)

⊕⊕⊕⊕
high

128 per 1000

111 per 1000
(85 to 142)

Moderate

144 per 1000

125 per 1000
(96 to 160)

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded by two levels for severe statistical heterogeneity.
2 Downgraded by one level for imprecision.

Figuras y tablas -
Summary of findings 10. S‐1 versus 5‐FU‐containing regimens for advanced gastric cancer
Comparison 1. Chemotherapy versus best supportive care

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall survival Show forest plot

3

184

Hazard ratio (Random, 95% CI)

0.37 [0.24, 0.55]

2 Time to progression Show forest plot

2

144

Hazard ratio (Fixed, 95% CI)

0.31 [0.22, 0.43]

Figuras y tablas -
Comparison 1. Chemotherapy versus best supportive care
Comparison 2. Combination versus single‐agent chemotherapy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall survival Show forest plot

23

4447

Hazard ratio (Fixed, 95% CI)

0.84 [0.79, 0.89]

2 Tumour response Show forest plot

18

2833

Odds Ratio (M‐H, Fixed, 95% CI)

2.30 [1.94, 2.72]

3 Time to progression Show forest plot

4

720

Hazard ratio (Random, 95% CI)

0.69 [0.55, 0.87]

4 Treatment‐related death Show forest plot

18

3876

Odds Ratio (M‐H, Fixed, 95% CI)

1.64 [0.83, 3.24]

Figuras y tablas -
Comparison 2. Combination versus single‐agent chemotherapy
Comparison 3. 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/cisplatin combinations (without anthracyclines)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall survival Show forest plot

4

579

Hazard ratio (Fixed, 95% CI)

0.74 [0.61, 0.89]

2 Tumour response Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3 Time to progression Show forest plot

1

Hazard Ratio (Fixed, 95% CI)

Subtotals only

Figuras y tablas -
Comparison 3. 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/cisplatin combinations (without anthracyclines)
Comparison 4. 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/anthracycline combinations (without cisplatin)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall survival Show forest plot

7

1147

Hazard ratio (Random, 95% CI)

0.82 [0.73, 0.92]

Figuras y tablas -
Comparison 4. 5‐FU/cisplatin/anthracycline combinations versus 5‐FU/anthracycline combinations (without cisplatin)
Comparison 5. Chemotherapy with irinotecan versus non‐irinotecan‐containing regimes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall survival Show forest plot

10

2135

Hazard Ratio (Fixed, 95% CI)

0.87 [0.80, 0.95]

1.1 Substitutive comparisons

6

826

Hazard Ratio (Fixed, 95% CI)

0.87 [0.75, 1.00]

1.2 Additive comparisons

3

500

Hazard Ratio (Fixed, 95% CI)

0.88 [0.76, 1.03]

1.3 Other comparisons

2

809

Hazard Ratio (Fixed, 95% CI)

0.87 [0.76, 1.00]

2 Tumour response Show forest plot

10

1266

Odds Ratio (M‐H, Random, 95% CI)

1.72 [1.24, 2.40]

2.1 Substitutive comparisons

6

756

Odds Ratio (M‐H, Random, 95% CI)

1.53 [0.93, 2.50]

2.2 Additive comparisons

3

345

Odds Ratio (M‐H, Random, 95% CI)

2.18 [1.25, 3.80]

2.3 Other Comparisons

2

165

Odds Ratio (M‐H, Random, 95% CI)

1.87 [0.89, 3.91]

3 Progression‐free survival Show forest plot

7

1640

Hazard Ratio (Fixed, 95% CI)

0.76 [0.69, 0.84]

3.1 Substitutive comparison

5

741

Hazard Ratio (Fixed, 95% CI)

0.85 [0.72, 1.00]

3.2 Additive comparisons

1

90

Hazard Ratio (Fixed, 95% CI)

0.51 [0.33, 0.77]

3.3 Other comparisons

2

809

Hazard Ratio (Fixed, 95% CI)

0.74 [0.66, 0.84]

4 Treatment‐related death Show forest plot

9

1979

Odds Ratio (M‐H, Random, 95% CI)

0.88 [0.23, 3.32]

5 Treatment discontinuation due to toxicity Show forest plot

9

1979

Odds Ratio (M‐H, Random, 95% CI)

1.00 [0.46, 2.20]

Figuras y tablas -
Comparison 5. Chemotherapy with irinotecan versus non‐irinotecan‐containing regimes
Comparison 6. Chemotherapy with docetaxel versus non‐docetaxel‐containing regimes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall survival Show forest plot

8

2001

Hazard Ratio (Fixed, 95% CI)

0.86 [0.78, 0.95]

1.1 Substitutive comparisons

3

479

Hazard Ratio (Fixed, 95% CI)

1.05 [0.87, 1.27]

1.2 Additive comparisons

4

1466

Hazard Ratio (Fixed, 95% CI)

0.80 [0.71, 0.91]

1.3 Other comparisons

1

56

Hazard Ratio (Fixed, 95% CI)

0.80 [0.46, 1.39]

2 Tumour response Show forest plot

9

1820

Odds Ratio (M‐H, Random, 95% CI)

1.37 [1.03, 1.83]

2.1 Substitutive comparison

4

525

Odds Ratio (M‐H, Random, 95% CI)

1.03 [0.71, 1.50]

2.2 Additive comparison

4

1235

Odds Ratio (M‐H, Random, 95% CI)

1.83 [1.45, 2.32]

2.3 Other comparisons

1

60

Odds Ratio (M‐H, Random, 95% CI)

0.33 [0.12, 0.96]

3 Time to progression Show forest plot

2

360

Hazard Ratio (Random, 95% CI)

1.06 [0.85, 1.32]

4 Progression‐free survival Show forest plot

5

1498

Hazard Ratio (Random, 95% CI)

0.76 [0.63, 0.91]

4.1 Substitutive comparisons

1

119

Hazard Ratio (Random, 95% CI)

1.15 [0.77, 1.72]

4.2 Additive comparison (PFS)

3

1323

Hazard Ratio (Random, 95% CI)

0.70 [0.61, 0.81]

4.3 Other comparisons

1

56

Hazard Ratio (Random, 95% CI)

0.94 [0.55, 1.60]

5 Treatment‐related death Show forest plot

7

2113

Odds Ratio (M‐H, Fixed, 95% CI)

1.10 [0.55, 2.20]

6 Treatment discontinuation due to toxicity Show forest plot

5

1066

Odds Ratio (M‐H, Random, 95% CI)

0.81 [0.53, 1.25]

Figuras y tablas -
Comparison 6. Chemotherapy with docetaxel versus non‐docetaxel‐containing regimes
Comparison 7. Chemotherapy with capecitabine versus 5‐FU‐containing regimes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall Survival Show forest plot

5

732

Hazard Ratio (Fixed, 95% CI)

0.94 [0.79, 1.11]

2 Tumour response Show forest plot

4

636

Odds Ratio (M‐H, Random, 95% CI)

0.85 [0.40, 1.79]

3 Time to progression Show forest plot

1

Hazard Ratio (Fixed, 95% CI)

Subtotals only

4 Progression‐free survival Show forest plot

4

647

Hazard Ratio (Random, 95% CI)

0.98 [0.77, 1.23]

5 Treatment‐related death Show forest plot

2

481

Odds Ratio (M‐H, Random, 95% CI)

1.88 [0.23, 15.15]

6 Treatment discontinuation due to toxicity Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Figuras y tablas -
Comparison 7. Chemotherapy with capecitabine versus 5‐FU‐containing regimes
Comparison 8. Chemotherapy with oxaliplatin versus the same regime including cisplatin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall Survival Show forest plot

5

1105

Hazard Ratio (Random, 95% CI)

0.81 [0.67, 0.98]

2 Tumour response Show forest plot

5

1081

Odds Ratio (M‐H, Fixed, 95% CI)

1.38 [1.08, 1.76]

3 Progression‐free survival Show forest plot

4

1034

Hazard Ratio (Random, 95% CI)

0.88 [0.66, 1.19]

4 Treatment‐related death Show forest plot

5

1132

Odds Ratio (M‐H, Fixed, 95% CI)

0.47 [0.17, 1.30]

5 Treatment discontinuation due to toxicity Show forest plot

3

970

Odds Ratio (M‐H, Random, 95% CI)

0.97 [0.44, 2.13]

Figuras y tablas -
Comparison 8. Chemotherapy with oxaliplatin versus the same regime including cisplatin
Comparison 9. Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall survival Show forest plot

3

482

Hazard Ratio (Fixed, 95% CI)

0.86 [0.71, 1.06]

2 Tumour response Show forest plot

3

482

Odds Ratio (M‐H, Fixed, 95% CI)

2.08 [1.37, 3.15]

3 Progression‐free survival Show forest plot

3

482

Hazard Ratio (Fixed, 95% CI)

0.74 [0.59, 0.93]

4 Treatment‐related death Show forest plot

3

482

Odds Ratio (M‐H, Fixed, 95% CI)

1.95 [0.73, 5.17]

5 Treatment discontinuation due to toxicity Show forest plot

2

234

Odds Ratio (M‐H, Fixed, 95% CI)

1.71 [0.79, 3.69]

Figuras y tablas -
Comparison 9. Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine)
Comparison 10. S‐1 versus 5‐FU‐containing regimes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall Survival Show forest plot

4

1793

Hazard Ratio (Fixed, 95% CI)

0.91 [0.83, 1.00]

2 Tumour response Show forest plot

7

1753

Odds Ratio (M‐H, Random, 95% CI)

1.73 [1.01, 2.94]

3 Progression‐free survival Show forest plot

4

1942

Hazard Ratio (Random, 95% CI)

0.85 [0.70, 1.04]

4 Time‐to treatment failure Show forest plot

5

1818

Hazard Ratio (Random, 95% CI)

0.88 [0.76, 1.01]

5 Treatment‐related deaths Show forest plot

4

1962

Odds Ratio (M‐H, Fixed, 95% CI)

0.56 [0.30, 1.06]

6 Treatment discontinuation due to toxicity Show forest plot

3

1726

Odds Ratio (M‐H, Fixed, 95% CI)

0.85 [0.63, 1.13]

Figuras y tablas -
Comparison 10. S‐1 versus 5‐FU‐containing regimes