Comparison of the incidence of febrile neutropenia in obese and normal weight breast cancer patients receiving myelosuppressive chemotherapy and prophylactic pegfilgrastim.

PURPOSE: Common breast cancer chemotherapy regimens are associated with a risk of febrile neutropenia, so prophylactic colony-stimulating factors are incorporated for high-risk patients. Filgrastim utilizes weight-based dosing; however, its sustained-release formulation utilizes fixed dosing. The purpose of this study is to determine whether obese breast cancer patients who receive pegfilgrastim are at increased risk of developing febrile neutropenia. METHODS: This study is a single-center, retrospective chart review. Breast cancer patients were categorized as normal weight (body mass index < 30), overweight (body mass index 30-39), or obese (body mass index ≥ 40). RESULTS: A total of 442 eligible patients were identified between 1 July 2012 and 19 May 2016. Twenty-eight were included in the obese group. Twenty-eight patients from each non-obese group were randomly selected to make up the overweight and normal weight groups. Incidence of febrile neutropenia was 1, 2, and 2 of 28 in the normal weight, overweight, and obese research groups, respectively. Increased use of antibiotics was observed in the obese group as compared to the normal and overweight groups (2, 1, 1, respectively; p = 0.0005). Median number of days on antibiotics was statistically significantly higher in the obese group at 10 days compared to the normal and overweight groups at seven days ( p = 0.03). CONCLUSION: Obese patients are not at increased risk of febrile neutropenia. However, they may have a lower threshold for febrile neutropenia and require more antibiotics after chemotherapy. Clinical significance of these results cannot be determined given the small sample size, so further multicenter studies are required.

A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.

PURPOSE: Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer. PATIENTS AND METHODS: Patients received either G+C (guadecitabine 30 mg/m2 s.c. once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS). RESULTS: Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs. 9.1 weeks in the G+C and TC groups, respectively; P = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; P = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group. CONCLUSIONS: Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection.