Docetaxel and Continuous-Infusion Fluorouracil vs Epirubicin, Cisplatin, and Fluorouracil for Advanced Gastric Adenocarcinoma

Abstract & Commentary

Synopsis: The combination of docetaxel and fluorouracil (DF) was compared with epirubicin, cisplatin and fluorouracil in a randomized Phase II trial in the treatment of advanced gastric cancer. The combinations proved equally efficacious but the toxicity profiles favored DF, with less nausea and vomiting. DF appears to be a promising regimen for this disease.

Source: Thuss-Patience PC, et al. J Clin Oncol. 2005;23: 494-501.

There remains no standard chemotherapy regimen for advanced gastric adenocarcinoma. Thuss-Patience and colleagues from Germany conducted a multicenter, randomized, phase II study for patients with advanced disease comparing 2 regimens (docetaxel and fluorouracil [DF] vs epirubicin, cisplatin, and fluorouracil ECF]). For the DF arm, docetaxel was administered at 75 mg/m2 on day 1 and fluorouracil was 200 mg/m2 by continuous infusion for days 1-21 of a 21 day cycle. For ECF, epirubicin 50 mg/m2 and cisplatin 60 mg/m2 were given on day 1 and fluorouracil was given at 200 mg/m2 on days 1-21 of a 21-day cycle.

Ninety patients were randomized and, in both arms, 43 of 45 patients were evaluable. In the DF arm, two patients (4.4%) experienced a confirmed complete tumor remission and 15 patients (33.3%) experienced a confirmed partial remission for an overall response rate (ORR) of 37.8%; 95% confidence interval (CI), 25.9%-51.9%. Two patients in the ECF arm (4.4%) showed confirmed complete remission and 14 (31.1%) showed confirmed partial remission (ORR, 35.6%; 95% CI, 24.8%-48.7%). Median survival was 9.5 and 9.7 months and the median time to tumor progression was 5.5 and 5.3 months for the DF and ECF arms respectively.

Although the toxicity was rarely severe, the profiles were different for the 2 treatment regimens. Major toxic effects included diarrhea, stomatitis, and leukopenia for the DF treated patients whereas it was nausea, vomiting and leukopenia for the ECF treated patients.

Thuss-Patience et al concluded that DF can be safely administered and that the regimen may prove to be less toxic by virtue of avoiding cisplatin.

Comment by William B. Ershler, MD

Although there is no standard treatment regimen for advanced gastric cancer, cisplatin-containing regimens are frequently employed in some combination with fluorouracil.1,2 ECF has been demonstrated to be an active combination and was superior to fluorouracil, doxorubicin, methotrexate (FAMTX)3 and this regimen has gained widespread use in this setting. However, toxicity has been problematic and alternative regimens are continuously sought for either improved efficacy or diminished toxicity.

In this light, the current phase II trial offers promise. The DF regimen has theoretical appeal because the drugs have demonstrated synergism in tumor models and, for the most part, toxicity is not overlapping. This is particularly true if the 21-day infusion of fluorouracil is chosen, as this has been shown to be associated with less myelotoxicity, a potential problem when fluorouracil is used with docetaxel. Indeed, although leukopenia was observed, it was comparable with ECF and manageable.

Of note, with regard to toxicity, the findings indicate a different profile between the 2 groups, with significantly less nausea and vomiting in the DF arm. By excluding cisplatin, it is likely that administration is less complex and the debilitating gastrointestinal toxicities diminished. These features, in light of the comparable efficacy to ECF, both in this study and from that reported in the literature, would suggest that DF is an appealing alternative to the commonly used cisplatin regimens, particularly in the out patient setting. Yet, the continuous infusion of fluorouracil remains a cumbersome approach, and one can’t help but wonder whether capecitabine might be equally efficacious in either of these regimens as a substitute. Hopefully, this notion will ultimately be tested in a well constructed clinical trial.

Refere nces

1. Wilke H, et al. Ann Oncol. 1996;7:46.

2. Rougier P, et al. Eur J Cancer. 1994;30A:1263-1269.

3. Webb A, et al. J Clin Oncol. 1997;15:261-267.

William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC, is Editor for Clinical Oncology Alert.