Chemotherapy Offers Little Benefit for Localized Stomach Cancer

By Crystal Phend
FLORENCE, Italy, March 12 -- Combination chemotherapy may not improve survival for nonmetastatic gastric cancer after surgery, results of a randomized clinical trial suggested.
Adjuvant chemotherapy failed to significantly increase disease-free or overall survival compared with surgery alone (HR 0.92 for recurrence and 0.90 for death), reported Francesco Di Costanzo, M.D., of the University Hospital Careggi here, and colleagues online in the Journal of the National Cancer Institute.
These findings, while disappointing, agree with those of other recent trials that showed no significant improvement with a variety of chemotherapy regimens for localized gastric cancer, the researchers said.
However, these findings are not the final word in the controversy over adjuvant chemotherapy in gastric cancer, said Aiwen Wu, M.D., and Jiafu Ji, M.D., both of the Beijing Cancer Hospital and Institute in Beijing, China, in an accompanying editorial.
The overall evidence is inconsistent but seems to support adjuvant chemotherapy, radiotherapy, or both whether postoperative or perioperative, especially for advanced stage disease, they said.
"Surgery alone is no longer the standard treatment for patients with resectable gastric cancer, independent of the patient population or the practice location," Drs. Wu and Ji concluded.
Based on promising results in advanced gastric cancer, the researchers randomized 258 patients with histologically proven, nonmetastatic stomach adenocarcinoma to receive either open-label chemotherapy or no further treatment after potentially curative surgery at 33 Italian centers.
Chemotherapy consisted of the PELF regimen, which included 30 mg/m2 epirubicin (Ellence) and 40 mg/m2 cisplatin (Platinol) on days one and five and 100 mg/m2 leucovorin (Wellcovorin) and 300 mg/m2 5-fluorouracil (Adrucil) on days one through four.
After a mean 73 months of follow-up, 139 patients had died (53% in the chemotherapy arm and 55% in the surgery alone group).
Overall, 128 patients developed recurrent disease (48% with chemotherapy versus 52% without), most commonly to the liver, peritoneum, or lymph nodes.
Five-year overall survival tended to be lower with chemotherapy than follow-up alone after surgery (47.6% versus 48.7%) as did median overall survival (56.7 versus 57.6 months).
However, disease-free survival at five years tended to be higher with adjuvant chemotherapy than with surgery alone (42.3% versus 41.6%, median 41.2 versus 34.3 months).
The differences between the regimens were not significant for either overall survival (HR of death 0.90, 95% CI 0.64 to 1.26) or disease-free survival (HR of recurrence 0.92, 95% CI 0.66 to 1.27).
Any potential benefit of adjuvant chemotherapy appeared to be concentrated among older patients.
Adjuvant chemotherapy was associated with a 42% reduction in recurrence among patients 60 and older (HR 0.58, 95% CI 0.35 to 0.96) but showed no advantage in recurrence among patients younger than 60 (HR 0.94, 95% CI 0.58 to 1.52).
Likewise for overall survival, chemotherapy tended to reduce risk of death for patients 60 and older (HR 0.62, 95% CI 0.37 to 1.01) but not for younger patients (HR 0.93, 95% CI 0.57 to 1.53).
Because these findings were an exploratory analysis, "the question of whether age is a real predictive factor for response or a marker of other factors needs to be investigated further," the researchers said.
Grade 3 or 4 toxicity among chemotherapy-treated patients included vomiting (21.1%), mucositis (8.4%), diarrhea (11.8%), leucopenia (20.3%), anemia (3.3%), and thrombocytopenia (4.2%).
The study was limited by underestimation of survival rates in the control group that resulted in lack of statistical power to show a benefit of less than 20% at five years.
"We are still not able to draw a definite conclusion as to whether adjuvant chemotherapy confers advantages to gastric cancer patients who have undergone curative resection," Drs. Wu and Ji concluded.
The study was funded by the National Council of Research and the Italian Association of Cancer Research. The researchers provided no information on conflicts of interest.
The editorialists reported support from the National Key Technology R&D Program and Beijing Municipal Science & Technology Commission NOVA program but no conflicts of interest.
Primary source: Journal of the National Cancer InstituteSource reference:Di Costanzo F, et al "Adjuvant chemotherapy in completely resected gastric cancer: A randomized phase III trial conducted by GOIRC" J Natl Cancer Inst 2008; 100: 388-398. Additional source: Journal of the National Cancer InstituteSource reference: Wu A, Ji J "Adjuvant chemotherapy for gastric cancer or not: A dilemma?" J Natl Cancer Inst 2008; 100.