경희대학교 의과대학·의학전문대학원

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(1)

Treatment of GI cancer

Esophagus Stomach Small intestine Colon cancer Rectal cancer Anal cancer Liver cancer Pancreatic cancer Biliary tract cancer

2008년

Treatment of Esophageal Cancer

• Surgery

– 5-year survival: 20%

• Radiation

• Chemotherapy

– Response rate: 30-60% – Cisplatin based combination

• Chemotherapy and radiation followed surgery

• Palliation

(2)

5-year Survival Rate

NEJM 2003;349:2241

Treatment of Gastric Carcinoma

• Surgery

– Only chance for cure – 5-year survival:

• Stage I (91%), II (72%), III (44%), IV (9%)

• Advanced stage

– Chemotherapy

• Response: 30-50%

• 5-FU, doxorubicin, mitomycin-C, cisplatin, methotrexate,

taxane

• Taxane, iritnotecan, oxaliplatin, capecitabine, TS-1

• Postoperative adjuvant chemotherapy: ?

– 5-FU, leukovorin with radiation (in USA)

(3)

Stage-Stratified Survival in Gastric Cancer

Stage-Adjusted 5-Year Overall Suvival(%)

No. Country IA IB II IIIA IIIB IV Western studies Hundahl 78 58 34 20 8 7 50,169 US Siewart 86 69 55 38 17 16 1,654 Germany Asian studies Kim 93 84 69 46 30 9 10,783 Korea Hayashi 95.8 77.7 51.2 30.1 14.8 6.2 940 Japan Morowaki 98.4 97.8 65 48.3 35.5 15.9 1,468 Japan

Treatment of Gastric Carcinoma

• Surgery

– Only chance for cure – 5-year survival:

• Stage I (91%), II (72%), III (44%), IV (9%)

• Advanced stage

– Chemotherapy

• Response: 30-50%

• 5-FU, doxorubicin, mitomycin-C, cisplatin, methotrexate • Taxane, irinotecan, oxaliplatin, capecitabine, S-1

• Postoperative adjuvant chemotherapy: ?

– 5-FU, leukovorin with radiation (in USA)

(4)

Lancet 2010;376:687

Treatment of Gastric Carcinoma

• Surgery

– Only chance for cure – 5-year survival:

• Stage I (91%), II (72%), III (44%), IV (9%)

• Advanced stage – Chemotherapy

• Response: 30-50%

• 5-FU, doxorubicin, mitomycin-C, cisplatin, methotrexate, taxane • Taxane, iritnotecan, oxaliplatin, capecitabine, TS-1

• Postoperative adjuvant chemotherapy: ?

– 5-FU, leukovorin with radiation (in USA)

– S-1(oral fluoropyrimidine) monotherapy for 1 yr (in Japan) – Oxaliplatin+capecitabine for 6 months (in Korea)

(5)

SWOG9008/INT0116 Study (2001)

• Stage IB-IV(M0)

• N=556 during 7 years accrual period

Macdonald JS et al. N Engl J Med 345:725, 2001

SWOG9008/INT0116

Relapse-free survival

Macdonald JS et al. N Engl J Med 345:725, 2001

Overall survival

(6)

SWOG9008/INT0116

• D2 resection was recommended • However, LN was dissected as follows

D0 54% D1 36% D2 10%

• NCI, NCCN recommendation

Adjuvant chemoradiotherapy for stage IB-IV(M0)

Macdonald JS et al. N Engl J Med 345:725, 2001

Treatment of Gastric Carcinoma

• Surgery

– Only chance for cure – 5-year survival:

• Stage I (91%), II (72%), III (44%), IV (9%)

• Advanced stage – Chemotherapy

• Response: 30-50%

• 5-FU, doxorubicin, mitomycin-C, cisplatin, methotrexate, taxane • Taxane, iritnotecan, oxaliplatin, capecitabine, TS-1

• Postoperative adjuvant chemotherapy: ?

– 5-FU, leukovorin with radiation (in USA)

– S-1(oral fluoropyrimidine) monotherapy for 1 yr (in Japan) – Oxaliplatin+capecitabine for 6 months (in Korea)

(7)
(8)

Disease-free survival Overall survival

Lancet 2012; 379:315-21

HR 0.56 95% CI 0.44-0.72 P<0.0001

Treatment of Gastric Carcinoma

• Surgery

– Only chance for cure – 5-year survival:

• Stage I (91%), II (72%), III (44%), IV (9%)

• Advanced stage – Chemotherapy

• Response: 30-50%

• 5-FU, doxorubicin, mitomycin-C, cisplatin, methotrexate, taxane • Taxane, iritnotecan, oxaliplatin, capecitabine, TS-1

• Postoperative adjuvant chemotherapy: ? – 5-FU, leukovorin with radiation (in USA)

– S-1(oral fluoropyrimidine) monotherapy for 1 yr (in Japan) – Oxaliplatin+capecitabine, phase 3 trial, ongoing (in Korea) • Preoperative (neoadjuvant) chemotherapy: ?

(9)

Phase II trials of neoadjuvant

chemotherapy in gastric cancer

Author Year No Response Operable Resectable Death

major cCR/pCR Ajani 1991 25 6 (25%) 0/0 25 (100%) 18 (72%) 1 Ajani 1993 48 15 (31%) 6/0 41 (85%) 37 (77%) 1 Ajani 1995 32 13 (41%) 3/1 29 (91%) 22 (76%) 1 Ajani 1999 30 10 (34%) 5/2 29 (97%) 25 (83%) 0 Kelsen 1996 56 (35-40%) ? 50 (89%) 34 (61%) 1 Crookes 1997 59 17 (41%) ?/5 56 (95%) 40 (68%) 2 cCR, clinical CR; pCR, pathologic CR

Treatment of Colorectal Cancer(1)

• Surgical resection

– Careful follow-up for 5 years

• CEA; every 3 months • P/E; every 6 months • colonoscopy; every 3 years

– Poor prognostic factor

• Stage, histologic grade, perforation,

venous invasion, preop CEA,

(10)

Treatment of Colorectal Cancer(2)

• Postoperative adjuvant therapy

– Chemotherapy

• Stage III

– 40% decrease in recurrence rates – 30% improvement in survival

• 5-FU+leucovorin, oxaliplatin+5-FU+leucovorin

– Irradiation

• Stage II/III rectal cancer

– Reduce regional recurrence rate: 20-25%

Treatment of Colorectal Cancer(3)

• Solitary hepatic metastasis

– Partial liver resection – 5-year survival: 25-30%

• Locally advanced rectal cancer

– Preoperative chemoradiation

• Metastatic disease

– Systemic chemotherapy – Response rate: 15-40%

– 5-FU+leucovorin, oxaliplatin, irinotecan, capecitabine – Cetuximab, bevacizumab

(11)

N Engl Med 2004;351:1731

Distant recurrence

Local recurrence

Treatment of Anal Cancer

• Radical surgery

– Abdominal-perineal resection, lymph node

sampling, permanent colostomy

– 5-year survival: 55-70%(20% in LNs

involvement)

• Irradiation+chemotherapy

– > 80% response with small lesion( < 3 cm)

– Cure: 70%

(12)

Treatment of Pancreatic Cancer

• Surgery

– 10% suitable for surgical resection, 30% R1 resection – Median survival 20-23 months, 5-year survival 20% – Good risk

• < 3cm, well-differentiation, lymph node-negative

– Postop adjuvant therapy

• 5FU+folinic acid(LV) • Gemcitabine

• CCRT(with 5FU) followed gemcitabine

• Unresectable disease

– Median survival: 6 months – Locally advanced:

• Gemcitabine followed by consolidation RT

– Chemotherapy

• Gemcitabine: improve quality of life

• Gemcitabine+erlotinib • Gemcitabine+capecitabine

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