Treatment Outcome of Cetuximab Compared with Cisplatin during Radical Radiotherapy for Locally Advanced Head and Neck Cancer
KS Law, RKY Wong, E Yu, ACK Cheng
Hong Kong J Radiol 2016;19:96-102
DOI: 10.12809/hkjr1615340
Objectives: To assess whether cetuximab (C225) is equivalent to cisplatin (CDDP) with concurrent radical radiotherapy (RT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) by comparing the treatment outcome of two patient cohorts treated in our institute.
Methods: Patients with LAHNSCC treated with weekly C225 and intensity-modulated radiotherapy (IMRT) with radical dose 70 Gy between March 2008 and June 2014 were retrospectively reviewed. Another cohort of patients with LAHNSCC treated with weekly CDDP and IMRT was selected for comparison, with matched age, sex, and primary tumour site. Treatment outcomes including crude local control rate, median duration of locoregional control, median overall survival, and toxicities were compared.
Results: The study cohort comprised 20 (95.2%) males and 1 (4.8%) female in each treatment arm. Their median age was similar in each cohort with 67 years in C225 group and 65 years in CDDP group. The median number of cycles received was 6 in C225 group versus 5 in CDDP group. Crude local control rate was 52.3% (11/21) in C225 group versus 61.9% (13/21) in CDDP group. The median duration of locoregional control was 15 months in C225 group and 48 months in CDDP group (hazard ratio [HR] = 1.19; 95% confidence interval [CI], 0.71-3.39; p = 0.747). The median overall survival was 27 months in C225 group versus 49 months in CDDP group (HR = 1.21; 95% CI, 0.48-3.07; p = 0.678). Acute severe skin toxicity (≥grade 3) was observed in 19% (n = 4) of the C225 group and 0% (n=0) of the CDDP group, while 38.1% (n = 8) of the CDDP group had grade 2 radiation dermatitis versus 14.3% (n = 3) of the C225 group. Two patients in the C225 group developed a grade 4 acute skin reaction with full-thickness dermis ulceration and bleeding. No grade 4 skin toxicity was observed in the CDDP group. Severe bone marrow toxicity (≥grade 3) occurred in 4.8% (n = 1) of the CDDP group, and CDDP-induced vomiting (grade 1-2) developed in 14.3% (n = 3) of patients and none had grade 3 or above toxicity. No bone marrow toxicity or vomiting occurred with C225 treatment. More treatment-induced renal toxicity was observed in the CDDP cohort (42.9%) compared with the C225 cohort (9.5%).
Conclusion: The results showed a trend of superior treatment outcomes for CDDP than C225 when combined with radical IMRT. If patients had good tolerance, CDDP concurrent with IMRT remains the standard of care for the treatment of LAHNSCC. C225 should be reserved for patients with poor functional status who cannot tolerate CDDP or where there are contraindications. In general, C225 concurrent with RT is well-tolerated, but there is a chance of grade 4 skin reactions. Prevention, early detection, and management of skin reaction to C225 are therefore vital. Whenever possible, C225 or CDDP should be added to radical RT for LAHNSCC for a gain in clinical outcome since evidence has shown poorer treatment results with RT alone.
中文摘要
比較西妥昔單抗（C225）和順鉑（CDDP）作為治療局部晚期頭頸部腫瘤的根治性放療結果
羅家雪、黃家仁、余洛汶、鄭志堅
目的：為局部晚期頭頸部鱗狀細胞癌（LAHNSCC）患者作根治性放療時，比較使用C225和CDDP的治療效果。
方法：回顧分析2008年3月至2014年6月期間每週接受強度調控放射治療（IMRT）並使用70 Gy C225的LAHNSCC患者。另一組年齡、性別及原發腫瘤位置相若的LAHNSCC患者則每週接受IMRT並使用CDDP。比較兩組患者的治療結果，包括粗局部控制率、局部控制的中位時間、總生存率中位數和毒性。
結果：每組患者包括20名（95.2%）男性和1名（4.8%）女性，患者年齡中位數相若（C225組67歲，CDDP組65歲）。放療週期中位數C225組6週，CDDP組5週。粗局部控制率C225組52.3%（11/21），CDDP組61.9%（13/21）。局部控制時間中位數C225組15個月，CDDP組48個月（風險比= 1.19；95%置信區間0.71-3.39；p=0.747）。總生存率中位數C225組27個月，CDDP組49個月（風險比= 1.21；95%置信區間0.48-3.07；p=0.678）。急性放射性皮炎（3級或以上）C225組19%（4例），CDDP組0%（0例）；CDDP組中38.1%（8例）有2級放射性皮炎，CDDP組則只有14.3%（3例）。C225組中兩名患者有4級急性放射性皮炎，並出現全層真皮潰瘍及出血。CDDP組則沒有4級急性放射性皮炎。CDDP組中4.8%（1例）出現骨髓毒性（3級或以上），14.3%（3例）因CDDP而誘發嘔吐（1-2級），但症狀均為輕微，並無3級或以上。C225組沒有出現骨髓毒性或嘔吐。與C225（9.5%）組相比，CDDP組有較多因治療引起的腎毒性病例（42.9%）。
結論：研究結果顯示CDDP結合根治性IMRT的治療效果，在數字上比C225結合根治性IMRT較佳。如果合適，應使用CDDP結合根治性IMRT治療LAHNSCC患者。對於那些功能狀態不佳、不能耐受CDDP或有禁忌症的患者，則可使用C225結合根治性IMRT治療。雖然一般來說，大多數患者能接受C225結合根治性IMRT，4級急性放射性皮炎仍可能發生。所以，接受C225治療前防止和及早發現並訂立治理方法至關重要。由於單單接受放療的治療效果不佳，可以的話，都應該加入C225或CDDP來改善治療效果。