ABSTRACT
Introduction: Desmoid-type fibromatosis (DF) are a group of rare (0.03% of total neoplasms) benign tumours arising from fibroblasts that can exhibit locally aggressive behaviour.1 Single agent oral vinorelbine (90 mg weekly for three consecutive weeks of each 28-day cycle) recently emerged as a simplified, less toxic and more manageable alternative to the standard pharmacological approach with two-weekly IV methotrexate and vinorelbine in patients with aggressive or refractory disease.2,3 This study aimed at describing the efficacy and safety of oral vinorelbine in a cohort of patients with DF in any line of treatment. Methods: This was a single-centre, retrospective study of patients treated with oral vinorelbine for DF over a period of 18 months (Jan 2020 to Jun 2021) within a specialised cancer centre. Patients who received at least 3 cycles of treatment (or until the first documented radiographic assessment, whatever occurred first) were included. The following information was collected from the electronic health care records system (Epic®): patient demographics (age, gender), number of previous treatment lines, and number of number of months on treatment (until closure of observations). Efficacy: clinical and radiographic reports were used to determine disease status as per RECIST A subgroup analysis of patients who were transitioned from other pharmacological options was also performed. Safety: routine full blood count and biochemistry weekly for the first three cycles, and once monthly thereafter were assessed for blood dyscrasias. Other side effects were also recorded. Results: Twenty-four patients were initially started on oral vinorelbine, of which 19 met the inclusion criteria (baseline and demographic characteristics summarised in table 1). Efficacy: Symptomatic improvement was observed in all cases (100%) shortly after initiation. Favourable radiographic findings (SD or better) were documented in 18 cases (94.73%). Only one patient (5.26%) experienced marginal increase in tumour size, but was maintained on treatment until further assessment, as still deriving clinical benefit. Additionally, all subjects in the subgroup who were transitioned from other pharmacologic options (9 patients) showed disease response. Safety: one episode of grade 3 neutropenia observed after seven cycles. Full blood counts and biochemistry parameters remained otherwise stable throughout treatment: one patient had low haemoglobin requiring multiple blood transfusions;this occurred in the context of poor baseline renal function and remained essentially unchanged throughout. The main reported toxicities were: diarrhoea (5 cases), nausea (grade 1 in 7 patients and grade 2 in one), fatigue (8), constipation (grade 2, 4 patients), and headaches and muscle pain (one case each). Discussion/conclusion: Single agent oral vinorelbine was found to be an effective treatment option for the management of newly diagnosed or refractory DF;this was also true for a subgroup of patients who received this to reduce hospital visits or after failure of a previous treatment line. Safety-wise, patients had stable blood counts and biochemical values throughout treatment, whereas most toxicities were mild and did not require discontinuation. These findings are in line with previous reports and underpin a paradigm shift in the management of DF in the post-COVID era.
ABSTRACT
Background: Systemic anti-cancer therapy (SACT) regimens used for sarcomas are some of the most intensive used in solid tumours. Febrile neutropenia (FN) is arguably the most significant complication from SACT. FN may lead to treatment delays and dose reductions, which may compromise dose intensity, and have a detrimental impact on efficacy outcomes. For regimens carrying an absolute FN risk <20%, current guidance supports the use of granulocyte-colony stimulating factor (GCSF) with every cycle (regardless of the occurrence of FN at any point during their treatment). Conversely, prophylactic antibiotics are recommended on cycle 1 and are only to be reintroduced if further FN episodes occur with subsequent cycles.1,2 Objective: To evaluate the adherence to national and local guidelines on the management of GCSF and prophylactic antibiotics in sarcoma patients undergoing SACT with FN rate of <20%. Methodology: Retrospective study conducted between February and May 2020 in adult and paediatric patients receiving the following regimes for soft tissue, bone, Ewing's sarcoma or rhabdomyosarcoma: MAP, DOX75/IFOS 9, VDC/IE, or treated according to the RMS 2005 trial protocols. Data collected: age, SACT regimen, allergy status, if ciprofloxacin prescribed (at cycle 1 and 2) and prescription details, if filgrastim prescribed and prescription details and if patients had FN with cycle 1. Exclusion criteria: paediatric patients treated elsewhere during the COVID-19 pandemic. Audit standards included: S1- 100% of patients receiving ciprofloxacin (500mg BD d7-15) unless penicillin/ quinolone allergy/resistance;S2- 100% of patients experiencing FN post-cycle #1 continue antibiotics for cycle 2, and antibiotics stopped in those who did not have FN;S3- 100% of patients receive GCSF (5-10 days commencing 24-72 h post-chemotherapy with cycles 1 & 2). Results: Twenty-one patients met the eligibility criteria, mean age 23.4 years and 33.3% of patients female (see Table 1 for baseline characteristics). S1: 73.5% of patients were prescribed ciprofloxacin with cycle 1 (in 9.5% of them starting dates and duration followed guidance);6 patients (28.5%) did not receive ciprofloxacin (with no documentation of allergy/ resistance). S2: 15 patients audited (6 excluded as did not meet S1), of which: 4 patients (26.6%) had the correct action taken for their second cycle vs 11 (73.3%) who did not (no FN at cycle 1 and continued on antibiotics inappropriately). S3: 20 patients (95.2%) were prescribed filgrastim for their first and second cycle, and 1 patient (4.7%) was prescribed peg-filgrastim. Conclusion: This study found marked differences in adherence to guidelines between antibiotics and GCSF prescribing: whilst the totality of patients received GCSF support with their two cycles, this decreased to ∼75% of patients being prescribed prophylactic antibiotics (in∼10% starting dates and duration exactly matched guidelines). Reasons for the comparatively low rate of antimicrobial prescribing may rely on prescriber preferences, treatment intent, performance status, or ciprofloxacin not pre-built into SACT regimens. Nonetheless, the relatively small patient numbers make it difficult to ascertain these factors. Additionally, 73% of patients had the incorrect action taken (discontinue if no FN vs continue if previous FN) for cycle 2..