Does adjuvant chemotherapy improve survival for women with early-stage uterine leiomyosarcoma?

OBJECTIVES: To examine whether adjuvant therapy after primary surgery for treatment of early-stage uterine leiomyosarcoma (LMS) improves recurrence and survival rates. METHODS: A multisite, retrospective study of women diagnosed with stage I-II high grade LMS from 1990-2010 was performed. All patients (pts) underwent primary surgery followed by observation (OBS), radiotherapy (RT), or chemotherapy (CT) postoperatively. RESULTS: One hundred eight patients were identified with long-term follow-up; 94 pts (87.0%) had stage I and 14 (13.0%) had stage II disease. The mean patient age was 55.4 years and mean BMI was 28.0. Thirty-four (31.5%) patients underwent OBS, 35 (32.4%) received RT, and 39 (36.1%) received chemotherapy. After a median follow-up of 41.8 months, a recurrence was diagnosed in 70.8%. Recurrence was evident in 25/34 (73.5%) OBS, 23/35 (65.7%) RT, and 28/39 (71.8%) of CT cohorts and was not different based on treatment (p=0.413). However, extra-pelvic recurrences were significantly higher in the RT (95.2%) than in the OBS (60%) or CT (64.3%) cohorts (p=0.012). Additionally, recurrences were more likely to be successfully treated or palliated in those who initially received CT (p=0.031). On multivariate analysis, stage (p<0.001) and chemotherapy (p=0.045) were associated with overall survival. CONCLUSIONS: Women with early-stage, high grade uterine LMS experience high recurrence rates and poor survival outcomes, irrespective of adjuvant therapy. These rates are higher than previously reported in the literature. Although women treated with CT had similar recurrence rates as those treated with OBS or RT, treatment with adjuvant chemotherapy may decrease the risk of extra-pelvic recurrence and improve survival.

Predictors of reduced relative dose intensity and its relationship to mortality in women receiving multi-agent chemotherapy for epithelial ovarian cancer.

OBJECTIVE: There is limited information concerning the role of relative dose intensity (RDI) on clinical outcomes in solid tumors. The objectives of our study were to evaluate the prognostic significance of RDI and predictors of reduced RDI in women with newly diagnosed advanced stage epithelial ovarian carcinoma (EOC) treated with platinum-based chemotherapy. METHODS: A multi-center retrospective study of women with FIGO stage III-IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy between 1995 and 2009 was conducted. Data were obtained to include the first four chemotherapy cycles administered. Outcomes included: (1) planned and delivered relative dose intensity (RDI), (2) progression-free (PFS) and overall (OS) survival. Survival estimates were based on Kaplan and Meier method, and multivariate analyses were based on logistic regression and Cox proportional hazards regression. RESULTS: Evaluable subjects included 325 women. With median follow-up of 34 months (range, 0.4-170), progression or recurrence was recorded in 241 (73.9%) and death in 179 (54.9%). In multivariate analysis, predictors of reduced planned RDI were: treatment off research protocols (odds ratio [OR]=4.3; P<0.001) and BSA >2m(2) (OR=6.14; P<0.001); predictors of reduced delivered RDI were: BMI over 30 kg/m(2) (OR=2.35; P=0.008) and use of carboplatin (OR=2.71; P=0.008). In multivariate analysis, the following factors were independently associated with OS: delivered RDI <85% (hazard ratio [HR]=1.71; P=0.003) and elevated CA-125 at cycle 1 (HR=2.29; P=0.017). CONCLUSION: In this retrospective analysis, reduced chemotherapy RDI for ovarian cancer was associated with lower OS, but not PFS, despite adjustment for established prognostic factors.

Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer.

OBJECTIVE: To identify factors that increase the risk of neutropenic events in women with advanced ovarian carcinoma receiving initial chemotherapy. METHODS: Multi-center retrospective study of women with FIGO stage III-IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy from 1995 to 2008. Outcomes were severe (SN; absolute neutrophil count [ANC]<500/mm(3)) and febrile neutropenia (FN; ANC<1000/mm(3) and temperature>38.1°C). Cumulative risk of neutropenic events was estimated by Kaplan Meier method. Multivariate analysis was by Cox proportional hazard regression. RESULTS: Three hundred twenty-six patients met inclusion criteria. There were 251 SN events among 140 (43%) patients and 24 FN events among 22 (7%) patients. Univariate predictors of SN were body surface area<2.0m(2) (p=0.03), body mass index (BMI)<30 kg/m(2) (p<0.01), Caucasian race (p<0.01), treatment on research protocols (p<0.01), non-carboplatin-containing regimens (p<0.01), and planned relative dose intensity (RDI)>85% of standard (p=0.02). Women over age 60 were more likely to develop FN (p=0.05). Multivariate predictors of SN were treatment on research protocols (hazard ratio [HR] 1.93; p<0.01), Caucasian race (HR 2.13; p=0.01), and planned RDI>85% (HR 1.69; p=0.05); predictors of FN were age>60 (HR 2.84; p=0.05) and non-carboplatin containing regimens (HR 4.06; p<0.01). CONCLUSION: While SN is fairly common, FN occurs infrequently in women with EOC undergoing taxane and platin-based chemotherapy and primary prophylactic growth factor support is not indicated. However, women older than 60 years of age receiving non-carboplatin containing regimens are at higher risk for FN and warrant closer surveillance.