A prospective randomised evaluation of G-CSF or G-CSF plus oral antibiotics in chemotherapy-treated patients at high risk of developing febrile neutropenia. Effect of granulocyte colony-stimulating factor (G-CSF) on chemotherapy-induced oral mucositis. Results of a randomized trial of granulocyte colony-stimulating factor in patients with infection and severe granulocytopenia. Granulocyte colony-stimulating factor (G-CSF) with or without a quinolone in the prevention of infection in cancer patients. Randomized phase II study of GM-CSF to reduce mucositis caused by accelerated radiotherapy of laryngeal cancer. Prevention of febrile leucopenia after chemotherapy in high-risk breast cancer patients: no significant difference between granulocyte-colony stimulating growth factor or ciprofloxacin plus amphotericin B. [Chemoprophylaxis of bacterial infections in granulocytopenic patients with new quinolone: a comparison of trimethoprim-sulfamethoxazole (ST) alone with ST plus ciprofloxacin]. Therapeutic efficacy by recombinant human granulocyte/monocyte-colony stimulating factor on mucositis occurring in patients with oral and oropharynx tumors treated with curative radiotherapy: a multicenter open randomized phase III study. Effect of granulocyte-macrophage colony-stimulating factor on oral mucositis in head and neck cancer patients after cisplatin, fluorouracil, and leucovorin chemotherapy.
Febrile neutropenia (FN) remains a major dose-limiting complication among patients treated with chemotherapy. Haematopoietic colony stimulating factors (G-CSF and GM-CSF) made possible a significant improvement in the management of FN, both in the therapeutic and in the prophylactic approach. The use of antibiotic prophylaxis also permits a definite reduction of severe infections during neutropenia. Nevertheless, the possible role of these two interventions for secondary prevention of FN is still unclear.
                We conducted a prospective randomised trial by comparing the efficacy of granulocyte-colony stimulating factor (G-CSF) and the association of G-CSF with oral antibiotics in the secondary prevention of FN. We included in our study those patients who, after an episode of FN, continued to be treated with the same chemotherapy without reduction of dose intensity. They were randomised into two groups: the first received G-CSF (group G; filgrastim, 5 microg/kg day), and the second was treated with an association of G-CSF and amoxicillin/clavulanate plus ciprofloxacin (group G/ACC).
                Forty-eight patients were randomised (group G: n=23 and group G/ACC: n=25). There was no recurrence of FN among the patients receiving G-CSF and only one episode in the combined therapy group (p=1). With regard to the side effects, there was no significant difference in the two groups.
                The use of G-CSF for the secondary prevention of FN is extremely effective and allows the maintenance of chemotherapy dose intensity. Our study showed that the addition of antibiotics does not seem to be required. In this study, the ability of granulocyte colony-stimulating factor (G-CSF) to treat or prevent chemotherapy-induced oral mucositis in patients with advanced breast cancer was evaluated. A total of 14 patients who received intraarterial (i.a.) adriamycin (ADM) preoperatively were divided into two groups according to whether or not G-CSF was given. Thus, group A (n = 7) was given G-CSF and group B (n = 7) was not. G-CSF therapy reduced both the incidence and duration of ADM-induced oral mucositis, and a positive correlation was also seen between the incidence of mucositis and ADM-induced leukopenia (< 2,000/mm3). Group A was further divided into two subgroups according to whether G-CSF was given after or before the leukopenia had dropped below 2,000/mm3: group A-1 (n = 3) and group A-2 (n = 4), respectively. ADM-induced mucositis was observed in two of the three patients in group A-1, but in none of the four patients in group A-2. These results strongly support the idea that G-CSF can effectively treat and prevent ADM-induced oral mucositis. A study was carried out to investigate the efficacy and toxicity of granulocyte colony-stimulating factor (G-CSF) in the treatment of infection in 119 severely granulocytopenic patients with hematological malignancies after intensive chemotherapy. Patients were assigned randomly to receive either antibiotics alone (ceftazidime, 2 g, i.v., every 8 h + amikacin 7.5 mg/kg, i.v., every 12 h) or the same antimicrobial regimen plus G-CSF (5 micrograms/kg/day, s.c.). Measurements were clinical improvement, eradication of infection and toxicity. Patients who received antibiotics plus G-CSF had more clinical responses (82 versus 60%), less superinfections (6 versus 20%), less mortality (5 versus 15 patients), less days in hospital (median 10 versus 27) and reduced antibiotic usage compared to patients who received only antibiotics. Hematological recovery (granulocytes > 1.0 x 10(9)/l) was also shorter in these patients (12 versus 23 days). Fungal infections occurred only in the group treated with antibiotics alone. Toxicity secondary to G-CSF was absent. We conclude that the addition of G-CSF to broad spectrum antibiotics is useful in selected patients with severe granulocyctopenia after intensive chemotherapy and infection, because if may prove the outcome in these patients. 59 patients who had earlier developed an infection following antineoplastic chemotherapy were randomised to receive either granulocyte colony-stimulating factor (G-CSF) alone or G-CSF+quinolone as prophylaxis during subsequent identical chemotherapy courses. 30 patients received 48 courses of G+CSF, while 29 patients received 44 courses of G-CSF+ofloxacin or ciprofloxacin. The overall infection rate was 23%. Patients with WHO grade IV leukopenia at the onset of prophylactic treatment developed infection in 61% of cases when on G-CSF, but only in 22% when on G-CSF+quinolone (P = 0.002). Patients with initial leukopenia of grade WHO III-I had only a 11% infection rate showing no significant difference between the treatment groups. The median duration of leukopenia < 1 x 10(9)/l was 4 days for patients receiving G-CSF alone and 3.5 days for those receiving additional quinolone. Patients developing infection had grade IV leukopenia for a median of 5 days. Both prophylactic treatments were well tolerated. We conclude that when prophylactic G-CSF is initiated at WHO grade IV leukopenia, addition of an oral quinolone reduces the risk of infection. Acute mucositis is dose-limiting in many accelerated radiotherapy schedules for head and neck cancer. Cytokines may be one means of reducing the severity of mucositis. A study was designed to assess the effect of subcutaneous molgramostin (granulocyte-macrophage colony stimulating factor; GM-CSF) injections on acute radiation morbidity in patients undergoing accelerated radiotherapy for laryngeal cancer. A prospective, randomized, observer-blind, controlled trial was conducted in 29 patients who were to receive radical radiotherapy over 3 weeks for early stage laryngeal cancer. Patients were randomized to receive 150 microg (approximately 2 microg kg(-1)) GM-CSF subcutaneously once daily for 14 days after the second week of radiotherapy, or no GM-CSF. Patients were assessed weekly for grade of mucositis, skin reactions and related parameters. The severity of mucositis was reduced in the GM-CSF arm (p<0.05). No other end-points reached statistical significance. Two patients failed to complete their courses of GM-CSF. Three developed influenza type symptoms and in one an allergic reaction was noted. There was no difference in tumour control rates. Subcutaneous GM-CSF reduced the severity of mucositis in patients undergoing accelerated radiotherapy. Injections were well tolerated. Further studies of cytokines are warranted, to assess the feasibility of increasing the total doses of accelerated radiotherapy given, with the aim of improving tumour cure rates. In a prospective randomized trial, 40 stage IV breast cancer patients undergoing intermediate high-dose chemotherapy (cyclophosphamide, 5-fluorouracil plus epirubicin or methotrexate), received either recombinant human G-CSF (rhG-CSF, group I) or ciprofloxacin and amphotericin B (CAB, group II) for prevention of febrile leucopenia (FL). In group I, seven of 18 patients developed FL (after 10/108 courses); in group II, seven of 22 patients (7/98 courses) (P = NS). Median hospitalization duration and costs were not different. RhG-CSF was 6.6 times more expensive per course than CAB. In conclusion, prophylactic CAB has similar efficacy to rhG-CSF in this setting, and is more cost-effective. Fifty-three granulocytopenic patients were studied in a randomized trial comparing trimethoprim-sulfamethoxaxole (ST) alone with ST + ciprofloxacin (CPFX) for prevention of bacterial infections. Seventeen febrile episodes occurred in 24 patients receiving ST alone, and 9 febrile episodes occurred in 29 patients receiving ST + CPFX. ST + CPFX was significantly effective than ST alone (p < 0.005). Although ST alone was effective to prevent infections in moderately granulocytopenic patients, it could not prevent infections in severely granulocytopenic patients whose minimal granulocyte count was less than 250/microliters during prophylactic treatment. In contrast, ST + CPFX was effective in severely as well as in moderately granulocytopenic patients. Clinically significant adverse reactions were not observed in both regimens. These results suggest that combination with ST and CPFX is more efficacious than ST alone for the prevention of bacterial infections in granulocytopenic patients. Previous studies suggested granulocyte-macrophage-colony stimulating factor (GM-CSF) might be beneficial for radiotherapy-induced mucositis. This trial examined the efficacy of GM-CSF in reducing mucositis of the oral cavity and/or oropharynx compared with conventional treatment.
                Mucositis, documented by a five-grade scale, was defined in patients with tumors of the head-neck. Centers were allowed to use their own preferred fractionation regimen. Randomization to treatment was decided before radiotherapy. Treatment with GM-CSF 4 microg/kg/d subcutaneous, started when patients displayed a mucositis score > or = 1.5.
                Ninety-two patients entered the study according to intention-to-treat principle. Twenty did not reach a mucositis index of 1.5. Sixty-one patients were included in the statistical analysis. Forty-five percent of the patients randomized to receive GM-CSF had a significant reduction of the mucositis more than one grade compared to 9% of the conventional treated.
                In severe mucositis, GM-CSF is more effective than conventional treatment. To evaluate prospectively the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the reduction of chemotherapy-induced oral mucositis.
                Twenty patients with stage IV squamous cell carcinoma of head and neck were studied. Two-cycles (periods) of identical doses of cisplatin, fluorouracil (5-FU), and leucovorin (PFL) chemotherapy with cisplatin 20 mg/m2/d, 5-FU 800 mg/m2/d, leucovorin 90 mg/m2/d by 96-hour continuous intravenous infusion every 3 weeks were given to each patient. After PFL chemotherapy, GM-CSF 4 micrograms/kg subcutaneously from days 5 to 14 or no therapy was given by a randomized self-controlled crossover study design. Oral mucositis was graded with modified Radiation Therapy Oncology Group criteria.
                In the first cycle of PFL chemotherapy, GM-CSF significantly reduced the incidence, mean duration, and mean area under the curve (AUC) of severe oral gross mucositis (grade > or = 3) compared with no therapy. These beneficial effects continued into the second cycle of PFL chemotherapy after crossover to no GM-CSF. The incidence of severe mucositis was reduced when GM-CSF was given in the second cycle of PFL. Analysis of variance indicated significant direct GM-CSF treatment effects on the mean AUC of gross/functional scores and duration of moderate gross mucositis (grade > or = 2) over both periods. There was a significant period effect in favor of giving GM-CSF in the first cycle of chemotherapy.
                GM-CSF can significantly reduce the severity and duration of chemotherapy-induced oral mucositis after PFL chemotherapy.
There is no evidence for or against antibiotics compared to G(M)-CSFs for the prevention of infections in cancer patients.