Karthaus M, Rosenthal C, Huebner G, Paul H, Elser C, Hertenstein B, Krauter J, Scharmann T, Geissler R G, Heil G, Ganser A
Department of Haematology and Oncology, Hannover Medical School, Germany.
Bone Marrow Transplant. 1998 Oct;22(8):781-5. doi: 10.1038/sj.bmt.1701434.
Oral mucositis is a dose-limiting toxicity of intensive chemotherapy. It is caused directly by the cytotoxic effect of chemotherapeutic agents and indirectly by sustained neutropenia. Severe oral mucositis is an important predisposing factor for life-threatening septic complications during aplasia. It also reduces quality of life. At present, no effective causal prophylaxis or treatment against oral mucositis is established. We performed a prospective randomised placebo-controlled trial using topical oral r-metHuG-CSF (filgrastim) in high-grade lymphoma patients treated according to the B-NHL protocol, which contains high-dose methotrexate and causes severe oral mucositis (WHO grades I-IV) in >50% of patients. Between August 1996 and July 1997, a total of 32 chemotherapy cycles were documented in eight patients (four male, four female). Mucosal erythema and ulceration were recorded. All patients assessed their oral pain and impact on swallowing daily, using a subjective scale from no to maximal discomfort (1-10). In addition, oral mucositis was assessed according to the WHO score. Filgrastim was administered in 16 cycles as a viscous mouthrinse (carboxymethylcellulose 2%, oleum citrii) 4 x 120 microg/day from days 10 to 16. Sixteen cycles were given to control patients, of these 14 with placebo, and another two cycles with no treatment. Severe mucositis (WHO grade III/IV) was documented in 21 of 32 cycles (65.5%). A difference of borderline significance was observed for the reduction of maximum severity of oral mucositis between G-CSF vs placebo (P = 0.058), with a reduction of WHO grade IV of 50% (four G-CSF vs eight control). The number of days in hospital was reduced significantly in the G-CSF group (P = 0.02). In conclusion, topical oral G-CSF mouthrinses may be beneficial to reduce oral mucositis.
口腔黏膜炎是强化化疗的剂量限制性毒性反应。它直接由化疗药物的细胞毒性作用引起，间接由持续性中性粒细胞减少所致。严重的口腔黏膜炎是再生障碍性贫血期间危及生命的脓毒症并发症的重要诱发因素。它还会降低生活质量。目前，尚未确立针对口腔黏膜炎的有效病因预防或治疗方法。我们进行了一项前瞻性随机安慰剂对照试验，在按照B-NHL方案治疗的高级别淋巴瘤患者中使用局部口服重组人粒细胞集落刺激因子（非格司亭），该方案包含大剂量甲氨蝶呤，会使超过50%的患者发生严重口腔黏膜炎（世界卫生组织分级I-IV级）。1996年8月至1997年7月期间，共记录了8例患者（4例男性，4例女性）的32个化疗周期。记录黏膜红斑和溃疡情况。所有患者每天使用从无不适到极度不适的主观量表（1-10）评估口腔疼痛及对吞咽的影响。此外，根据世界卫生组织评分评估口腔黏膜炎。在第10至16天，16个周期使用非格司亭作为黏性漱口水（2%羧甲基纤维素，柠檬油），每天4次，每次120微克。16个周期给予对照患者，其中14个周期给予安慰剂，另外2个周期不进行治疗。32个周期中有21个记录到严重黏膜炎（世界卫生组织III/IV级）（65.5%）。观察到非格司亭组与安慰剂组相比，口腔黏膜炎最大严重程度的降低有临界显著性差异（P = 0.058），世界卫生组织IV级降低了50%（非格司亭组4例 vs 对照组8例）。非格司亭组的住院天数显著减少（P = 0.02）。总之，局部口服非格司亭漱口水可能有助于减轻口腔黏膜炎。
