Journal of the National Cancer Institute Advance Access published online on March 11, 2008
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn054
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© The Author 2008. Published by Oxford University Press.
ARTICLES |
Adjuvant Chemotherapy in Completely Resected Gastric Cancer: A Randomized Phase III Trial Conducted by GOIRC
On behalf of Italian Oncology Group for Cancer Research
Affiliations of authors: Oncologia Medica (FDC, SG) and Dipartimento di Patologia Umana ed Oncologia (LM), Azienda Ospedaliero Universitaria Careggi, Florence, Italy; Oncologia Medica, Potenza (LM, DB); Oncologia Medica, Reggio Emilia (GB); Oncologia Medica, Ospedali Riuniti, Bergamo (RL); Oncologia Medica, Città di Castello (SB); Oncologia Medica B, Università La Sapienza, Roma (EC); Oncologia Medica A, San Raffaele-IRE, Roma (PC); Clinica di Oncologia Medica, Ancona (RB); Dipartimento Medicina Sperimentale, Università la Sapienza-Umberto I Roma (ST); Istituto di Patologia Generale, Università di Firenze (LM); Istituto di Ricerche Farmacologiche Mario Negri Milano (AA, IF); Divisione di Oncologia Medica, Perugia (MT)
Correspondence to: Francesco Di Costanzo, MD, Unit of Medical Oncology, Azienda Ospedaliero Universitaria Careggi, Viale Pieraccini 17, 50139 Florence, Italy (e-mail: dicostanzofrancesco{at}tiscali.it).
Background: Complete surgical resection of gastric cancer is potentially curative, but long-term survival is poor.
Methods: Patients with histologically proven adenocarcinoma of the stomach of stages IB, II, IIIA and B, or IV (T4N2M0) and treated with potentially curative surgery were randomly assigned to follow-up alone or to intravenous treatment with four cycles (repeated every 21 days) of PELF (cisplatin [40 mg/m2, on days 1 and 5], epirubicin [30 mg/m2, days 1 and 5], L-leucovorin [100 mg/m2, days 1–4], and 5-fluorouracil [300 mg/m2, days 1–4] in a hospital setting. Frequencies and severity of adverse events were determined. Overall survival (OS) and disease-free survival (DFS) were compared between the treatment arms using Kaplan–Meier analysis and a Cox proportional hazards regression model. All statistical tests were two-sided.
Results: From January 1995 through September 2000, 258 patients were randomly assigned to chemotherapy (n = 130) or surgery alone (n = 128). Patient characteristics were well balanced between the two arms. Among those who received chemotherapy, grade 3 or 4 toxic effects including vomiting, mucositis, and diarrhea were experienced by 21.1%, 8.4%, and 11.8% of patients, respectively. Leucopenia, anemia, and thrombocytopenia of grade 3 or 4 were experienced by 20.3%, 3.3%, and 4.2% of patients, respectively. After a median follow-up of 72.8 months, 128 patients (49.6%) experienced recurrence and 139 (53.9%) deaths were observed, one toxicity-related. Relative to treatment with surgery alone, adjuvant chemotherapy did not increase disease-free survival (hazard ratio [HR] of recurrence = 0.92; 95% confidence interval [CI] = 0.66 to 1.27) or overall survival (HR of death = 0.90; 95% CI = 0.64 to 1.26).
Conclusions: Our results failed to provide proof of an effect of adjuvant chemotherapy with PELF on overall survival or disease-free survival. The estimated effect of chemotherapy (10% reduction in the hazard of death or relapse) is modest and consistent with the results of meta-analyses of adjuvant chemotherapy without platinum agents.
| CONTEXT AND CAVEATS Prior knowledge The effectiveness of adjuvant therapy for patients who are surgically treated for gastric cancer was not clear. A combination of epirubicin, leucovorin, 5-fluorouracil, and cisplatin, the PELF regimen, had shown some benefit over other regimens in terms of patient response. Study design Randomized clinical trial comparing PELF chemotherapy and follow-up alone in patients with completely resected gastric cancer. Contribution The PELF regimen was not effective at improving patient survival in an adjuvant setting. Implications New strategies and further study will be required to improve survival in patients who are surgically treated for gastric cancer. Limitations This study was not powered to detect very modest differences in patient outcomes between the two treatment arms.
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Manuscript received July 30, 2007; revised December 22, 2007; accepted February 4, 2008.
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J Natl Cancer Inst 2008 100: 376-377.
J Natl Cancer Inst 2008 100: 375.
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