What is the effectiveness of chemotherapy for a patient with gastric malignancy?

Effectiveness of Chemotherapy for Gastric Malignancy

Chemotherapy is highly effective for gastric malignancy and significantly improves survival and quality of life compared to best supportive care alone, with the specific approach depending on disease stage: perioperative chemotherapy is the standard for resectable disease, while palliative chemotherapy extends median survival from 5 to 8 months in metastatic disease. 1, 2

Effectiveness in Resectable/Locoregional Disease

Perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) is the current standard and demonstrates superior outcomes for resectable gastric cancer, improving 5-year survival from 23% to 36% compared to surgery alone. 3, 4

• The MAGIC trial established that perioperative ECF (epirubicin, cisplatin, 5-FU) chemotherapy significantly improves progression-free and overall survival, with 5-year survival rates of 36% versus 23% with surgery alone. 3
• Surgery alone is insufficient therapy for most patients with resectable gastric cancer in Western populations. 3
• Perioperative chemotherapy is a Category 1 recommendation for medically fit patients with resectable locoregional gastric adenocarcinoma. 3

Postoperative Chemoradiation Alternative

For patients who undergo surgery without preoperative chemotherapy, postoperative chemoradiation is an effective alternative:

• The Intergroup-0116 trial demonstrated that adjuvant 5-FU/leucovorin plus concurrent radiotherapy (45 Gy) improved median survival from 27 to 36 months and 5-year overall survival from 41% to 50% (P=0.005). 3
• This benefit persists after more than 10 years of follow-up with a hazard ratio of 1.32 favoring chemoradiation. 3
• This approach is standard in the United States but less accepted in Europe due to concerns about the quality of surgery in the trial (54% underwent less than D1 lymphadenectomy). 3

Effectiveness in Advanced/Metastatic Disease

Palliative chemotherapy provides substantial survival benefit and quality of life improvement in metastatic gastric cancer for patients with good performance status (ECOG ≤2 or Karnofsky ≥60%). 1, 2

Survival Benefits

• Chemotherapy extends median overall survival from 5 months with best supportive care alone to 8 months with chemotherapy plus best supportive care. 1, 2
• Time to progression improves from 2 months to 5 months with chemotherapy. 2
• Quality of life is improved or prolonged in 45% of chemotherapy patients versus 20% with best supportive care alone. 2

First-Line Regimens and Response Rates

For HER2-positive disease (22% of gastric cancers), trastuzumab plus cisplatin and fluoropyrimidine is the standard, improving median overall survival from 11.1 to 13.8 months (HR 0.74, P=0.0048). 3, 1, 5

• HER2 testing must be performed on all patients with advanced gastric cancer before initiating treatment. 3, 1
• For HER2-negative disease, FOLFOX or CAPOX doublets are preferred, with median overall survival of 11.2 months (superior to ECF with HR 0.80, P=0.02). 1
• Single-agent response rates range from 10-30%, while combination chemotherapy achieves 30-60% response rates. 6
• The TCF regimen (docetaxel, cisplatin, fluorouracil) demonstrated significantly longer time to progression (5.6 vs 3.7 months, p=0.0004) and overall survival (9.2 vs 8.6 months, p=0.0201) compared to cisplatin/fluorouracil alone. 5

Second-Line Therapy Effectiveness

Ramucirumab plus paclitaxel is the preferred second-line regimen for patients maintaining ECOG PS ≤2, extending median overall survival to 9.6 months versus 7.4 months with paclitaxel alone. 1

• Irinotecan monotherapy improves survival versus best supportive care (median OS 4.0 vs 2.4 months, HR 0.48, P=0.023). 1
• Docetaxel, paclitaxel, and irinotecan all demonstrate activity as second-line agents. 3

Patient Selection Criteria

Performance status is the critical determinant of chemotherapy benefit:

• Patients with ECOG PS 0-2 or Karnofsky ≥60% should receive chemotherapy as it provides survival and quality of life benefits. 1, 2
• Patients with ECOG PS ≥3 or Karnofsky <60% should receive best supportive care only, as chemotherapy provides no benefit and increases toxicity. 1, 2
• Age alone is not a contraindication; elderly patients benefit from chemotherapy, though dose reduction (60% of standard capecitabine/oxaliplatin) is noninferior with better tolerability. 1

Common Pitfalls and Caveats

The most critical pitfall is treating patients with poor performance status with chemotherapy, as this increases toxicity without survival benefit. 2

• Failure to test HER2 status results in missing the opportunity for trastuzumab therapy, which provides a 2.7-month survival advantage in HER2-positive patients. 3, 1
• In the adjuvant setting, the benefit of postoperative chemoradiation may be less pronounced after optimal D2 lymphadenectomy compared to suboptimal surgery. 3
• Best supportive care should always be provided concurrently with chemotherapy, not as an alternative, including symptom management, nutritional support, and psychosocial care. 2
• Imminently dying patients (weeks to days to live) are not candidates for chemotherapy regardless of performance status. 2