Effect of topical oral G-CSF on oral mucositis: a randomised placebo-controlled trial

Abstract

Summary: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 highgrade lymphoma patients treated according to the B-NHL protocol, which contains high-dose methotrexate and causes severe oral mucositis (WHO grades I-IV) in Ͼ50% 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 × 120 g/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. Keywords: oral mucositis; topical G-CSF; high-grade lymphoma; randomised trial Oral mucositis is a major side-effect of chemotherapy. It occurs with an incidence of about 40%. 1,2 The causes of

Systematic review of cytokines and growth factors for the management of oral mucositis in cancer patients

“…Crawford et al [50] reported a beneficial effect, whereas a randomized controlled trial by Patte et al [51] found that G-CSF was not effective to prevent mucositis in this setting (Table 1). In addition, no guideline could be provided for the use of a G-CSF mouthwash for the prevention of CT-induced oral mucositis [52].…”

Prophylaxis and treatment of chemo- and radiotherapy-induced oral mucositis – are there new strategies?

“…37 Disruption of the intact mucosa tissue and impairment of the mucosal barrier is considered to be an important risk factor for infection in the neutropenic host. [9][10][11][12] With the frequent use of antibacterial prophylaxis for patients with prolonged neutropenia, a decreasing frequency of bacterial infections is observed in patients with oral mucositis. 38 However, the prevalence of an oral focus in febrile septicaemia has been reported in 25-50%.…”

“…11 Data from pilot studies of topical GM-CSF for prophylaxis and treatment of oral mucositis are also available (Table 4). [128][129][130][131][132][133] Topical treatment with GM-CSF enhanced wound contraction and healing of contaminated wounds in animal models.…”

“…Mucositis usually starts 5-7 days after the onset of chemotherapy and first presents with erythema of the soft palate, 11 the buccal mucosa, the ventral surface of the tongue, and the floor of the mouth. 32 Erythema is frequently followed by edema and ulceration, ranging from aphthous-like lesions to generalised desquamation, maximal on days 11-14.…”

“…Disruption of the mucosal barrier opens the door to consecutive, often life-threatening infectious complications during neutropenia. [9][10][11][12] From the patient's point of view, oral mucositis is one of the major distressing complications of cancer therapy. In addition, severe oral mucositis and subsequent complications may lead to a delay in cancer therapy and dosereduction of antineoplastic agents, which might result in an unfavourable outcome of the cancer treatment.…”