The use of antibiotic prophylaxis in neutropenic patients remains controversial. The main arguments against prophylaxis are the lack of survival benefit and the risk of inducing antibiotic resistance. At present, clinical guidelines advise against routine use of antibiotic prophylaxis and current practice is to commence broad-spectrum antibiotics at the onset of fever in the neutropenic patient. However hospitalization, investigations and treatment all impact on resources as well as affecting patient quality of life, often resulting in chemotherapy delays and dose reductions. The benefits of prophylactic antibiotics have been emphasized by two major double-blind, placebo controlled trials with levofloxacin with very significant reductions in all infection-related events. Furthermore, the meta-analysis confirms a survival advantage and this is greatest with the use of fluoroquinolones. These benefits must be weighed against the problem of emerging antibiotic resistance. It has been shown that antibiotic prophylaxis does induce resistant organisms, but some studies have shown that the impact on clinical outcomes may not be as great as expected. Current evidence supports antibiotic prophylaxis with fluoroquinolones in acute leukaemia and high-dose chemotherapy patients, commencing at the same time as chemotherapy. Febrile episodes are much commoner with the first cycle in patients with solid tumours or lymphoma having moderately myelosuppressive chemotherapy, and these patients should be offered prophylaxis for at least the first cycle of chemotherapy. Further work is ongoing to facilitate the selection of patients with the greatest chance of benefit so that prophylaxis can be used efficiently.
5046 Background: Neo-Escape was designed to exploit fully the modest non-cross resistance of carboplatin (CBDCA) and paclitaxel (ptx) in an extended sequential regimen, with dose-dense ptx, and address feasibility of combining gemcitabine (gem) with either CBDCA or ptx. Methods: A randomised phase II trial in patients (pts) with untreated (FIGO stage 3C/4) inoperable ovarian, fallopian, or primary peritoneal carcinoma to assess feasibility of two regimens of sequential neoadjuvant-then-adjuvant chemotherapy (CT); (a) CBDCA AUC 2.5 and gem 1000mg/m2 repeated days 1 and 8 q 3 wks x 6 cycles, then ptx 175mg/m2 q 2 wks x 6 cycles (CG-P) or (b) CBDCA AUC 6 q 3 wks x 6 cycles, then ptx 175mg/m2 and gem 2000mg/m2 q 2 wks x 6 cycles (C-PG). All pts were considered for delayed 1o debulking surgery after neoadjuvant CT. The 1o feasibility outcome was % pts completing 12 cycles of CT. Using Fleming’s single stage procedure 44 patients on each arm were needed to test null hypothesis of feasibility ≤60% with 5% 1-sided significance level and 90% power. 2o outcomes included safety, PFS and ORR. Pts were stratified by serum albumin, stage and tumor differentiation. Results: 75 pts were recruited Sept 2007 - May 2011 (28 CG-P; 47 C-PG), median age 62 yr (range 21-75). Recruitment to CG-P closed early due to futility. 52% had albumin >35g/L, 68% FIGO stage 3C and 80% poorly differentiated tumors. 64% on CG-P and 55% on C-PG had debulking surgery as planned and a further 4% on CG-P and 13% on C-GP after completion of all CT. For CG-P 35% achieved 0cm, 35% <1cm and 30% ≥ 1cm residuum; for C-GP 34% 0cm, 13% <1cm and 34% ≥1cm, 19% TBC. 14/28 pts on CG-P completed all 12 cycles (feasibility 50%; 95% CI 31-67%); 37/47 pts on C-PG (feasibility 79% (95% CI 64-88). Main reason for early discontinuation was toxicity on CG-P and disease progression on C-PG. Similar proportions of pts on each arm had dose reductions (68%) or delays (86% on CG-P; 89% on C-PG), mainly for toxicity. 82% of pts experienced grade 3/4 toxicity on CG-P; 72% on C-PG. Median PFS for CG-P is 14.3 mths (95% CI 11.6-15.7mths) and 13.0 mths (95% CI 11.5-15.4mths) for C-PG. Conclusions: CG-P was not feasible at these doses using pre-specified criteria, but C-PG is feasible.
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