Radiation Oncology/Stomach/Unresectable

Unresectable Gastric Cancer

Chemo-RT

• For medically-inoperable or for palliation.
• 12-20% may be long term survivors.

• Mayo Clinic (1960's) -- RT alone vs. RT + 5-FU
  • Randomized. 64 patients with unresectable cancers of the stomach, pancreas, and large bowel. Arm 1) EBRT 35-40 Gy vs. Arm 2) Same EBRT + concurrent 5-FU
  • 1969 PMID 4186452 -- "Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer." (Moertel CG, Lancet. 1969 Oct 25;2(7626):865-7.)
    • Outcome: median OS RT alone 6.3 months vs. chemo-RT 10.4 months (SS); 1-year OS 6% vs. 22%
    • Conclusion: Concurrent chemo-RT significantly augments RT alone
  • Comment: First study to show a benefit for combined chemo/RT

• GITSG - PMID 6176313 — "A comparison of combination chemotherapy and combined modality therapy for locally advanced gastric carcinoma." Cancer. 1982 May 1;49(9):1771-7.
  • 90 pts. 5-FU/MeCCNU + RT vs Chemo alone for node-positive or T4 tumors. Allowed resection (majority had residual disease).
  • Closed early due to increased deaths in chemo/RT arm; however, with longer follow-up, there was a plateau of the survival curve with 18% surviving beyond 5 years -- this benefit was in those who had their tumor resected.
  • Comment: Supported rationale for adjuvant trials in patients at high risk for relapse because chemo/RT was shown to control microscopic disease

Advanced

• Multinational V325 (1999-2003) -- DCF vs. CF
  • Randomized, multinational. 445 patients with advanced gastric or GE junction CA treated with docetaxel 75 mg/m2, cisplatin 75 mg/m2, fluorouracil 750mg/m2 C.I. (DCF) vs. cisplatin 100 mg/m2 and fluorouracil 1000 mg/m2 (CF)
  • 2-years, 2006 PMID 17075117 -- "Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group." (Van Cutsem E, J Clin Oncol. 2006 Nov 1;24(31):4991-7.)
    • 2-year outcome: OS: DCF 18% vs. CF 9% (SS)
    • Toxicity: Grade 3-4 events (neutropenia, stomatitis, diarrhea, lethargy) DCF 69% vs. CF 59%
  • Clinical benefit, 2007 PMID 17664467 -- "Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: the V-325 Study Group." (Ajani JA, J Clin Oncol. 2007 Aug 1;25(22):3205-9.)
    • Outcome: Time-to-KPS-worsening DCF 6.1 months vs. CF 4.8 months (SS); no difference in weight loss or appetite change
    • Conclusion: Addition of D to CF improves clinical benefit
  • Quality of life, 2007 PMID 17664468 -- "Quality of life with docetaxel plus cisplatin and fluorouracil compared with cisplatin and fluorouracil from a phase III trial for advanced gastric or gastroesophageal adenocarcinoma: the V-325 Study Group." (Ajani JA, J Clin Oncol. 2007 Aug 1;25(22):3210-6.)
    • QLQ-C3 and EQ-5D questionnaries. QOL preserved for DCF vs. CF (SS)
  • Conclusion: DCF provides improved OS, clinical benefit, and quality of life over CF

• EORTC GI 213 (1992-1995) -- ECF vs. FAMTX
  • 1997 PMID 8996151 -- "Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer." (Webb A, J Clin Oncol. 1997 Jan;15(1):261-7.)
  • Randomized. 274 patients, inoperable carcinoma of esophagus, GE junction, or stomach. Arm 1) ECF x8 cycles vs. Arm 2) FAMTX x8 cycles
    • Outcome: median OS ECF 9 months vs. FAMTX 6 months (SS); 1-year OS 36% vs. 21% (SS)
    • Toxicity: tolerable, 3 toxic deaths
    • Conclusion: ECF results in survival advantage and tolerable toxicity