Article révisé par les pairs
Résumé : Background. Platinum-based concurrent chemoradiation (CCRT) improves locoregional control and overall survival of locoregionally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) when compared to radiotherapy alone, but this approach is hampered by significant toxicity. Therefore, alternativeways to enhance the radiation effects are worth investigating. Gemcitabine(2′,2′-difluorodeoxycytidine), in addition to its activity against a variety of solid tumors, including SCCHN, is one of the most potent radiosensitizers, and it has an overall favorable safety profile. In thispaper, the clinical experience with gemcitabine-based chemoradiation in the treatment of patients with LA-SCCHN is reviewed. Methods. We conducted a review of the literature on the clinical experience with radiotherapy combined with either single-agent gemcitabine or gemcitabine/cisplatin-based polychemotherapy for the treatment of patients with LA-SCCHN. Wealso searched abstracts in databases of major international oncology meetings from the last 20 years. A meta-analysis was performed to calculate pooled proportions with 95% confidence intervals (CIs) for complete response rate and grade 3–4 acute mucositis rate. Results. Atotal of13paperswereeligible for theliteraturereview. For schedules using a gemcitabine dose intensity (DI) below 50mg/m2 perweek,the completeresponseratewas86%(95%CI, 74%–93%) with grade 3–4 acute mucositis rate of 38% (95% CI, 27%–50%) and acceptable late toxicity. In one of the studies employing such low DIs, survival data were provided showing a 3-year overall survival of 50%. Comparedwith DI ≥ 50mg/m2 per week, there was no difference in the complete response rate (71%; 95% CI, 55%–83%; p =.087) but a significantly higher (p<.001) grade 3–4 acute mucositis rate of 74% (95% CI, 62%–83%), often leading to treatment interruptions (survival data provided in 8 studies; 3-year overall survival, 27%–63%). Late toxicity comprising mainly dysphagia was generally underreported, whereas information about xerostomia and skin fibrosis was scarce. Conclusion. This review highlights the radiosensitizing potential of gemcitabine and suggests that even very low dosages (less than 50mg/m2 perweek) provide a sufficient therapeutic ratio and thereforeshouldbefurtherinvestigated. Refinementsinradiationschemes, including intensity-modulated radiation therapy, in combination with low-dose gemcitabine and targeted agents, such as cetuximab, are currently being investigated.

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