taxane and Cystadenocarcinoma--Serous

Low-grade serous carcinoma of the ovary/peritoneum (LGSC) is relatively chemoresistant in the adjuvant, neoadjuvant, and recurrent settings. We sought to expand our prior work and evaluate response rates of women with LGSC to neoadjuvant chemotherapy (NACT) compared to women with high-grade serous carcinoma of the ovary/peritoneum (HGSC).. Thirty-six patients with LGSC who received NACT were matched to patients with HGSC. A single radiologist re-reviewed pre- and post-NACT imaging for response using RECIST 1.1. Pre- and post-NACT CA-125 values were compared using paired t-tests. Kaplan-Meier estimates of progression free survival (PFS) and overall survival (OS) were performed.. All patients received neoadjuvant platinum-based regimens. LGSC patients received a median of 5 cycles (range 3-9), HGSC patients received a median of 4 cycles (range 3-9). Interval cytoreductive surgery was performed in 29/36 (81%) of LGSC and 32/36 (89%) HGSC patients. Complete cytoreduction was reported and achieved in 11/29 (38%) of LGSC patients and 24/32 (75%) of HGSC patients (p = 0.002). Median pre- and post-treatment CA-125 levels for LGSC patients were 295.5 U/mL and 144 U/mL (52% decrease) (p < 0.001). The median pre- and post-treatment CA-125 levels for HGSC patients were 767.5 and 35.6 (96% decrease) (p < 0.001). For LGSC patients, 4/36 (11%) had partial response (PR), 30/36 (83%) had stable disease (SD), and 2/36 (6%) had progressive disease (PD). In HGSC patients, 27/36 (75%) had PR, and 9/36 (25%) SD. Median PFS for LGSC patients was 18.5 months and median OS was 47.4 months.. This study provides further evidence of relative chemoresistance of LGSC in patients treated with NACT.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; CA-125 Antigen; Cystadenocarcinoma, Serous; Drug Resistance, Neoplasm; Female; Humans; Ki-67 Antigen; Membrane Proteins; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms; Progression-Free Survival; Response Evaluation Criteria in Solid Tumors; Taxoids; Young Adult

Individual mutations in the tumor suppressor TP53 alter p53 protein function. Some mutations create a non-functional protein, whereas others confer oncogenic activity, which we term 'oncomorphic'. Since mutations in TP53 occur in nearly all ovarian tumors, the objective of this study was to determine the relationship of oncomorphic TP53 mutations with patient outcomes in advanced serous ovarian cancer patients. Clinical and molecular data from 264 high-grade serous ovarian cancer patients uniformly treated with standard platinum- and taxane-based adjuvant chemotherapy were downloaded from The Cancer Genome Atlas (TCGA) portal. Additionally, patient samples were obtained from the University of Iowa and individual mutations were analyzed in ovarian cancer cell lines. Mutations in the TP53 were annotated and categorized as oncomorphic, loss of function (LOF), or unclassified. Associations between mutation types, chemoresistance, recurrence, and progression-free survival (PFS) were calculated. Oncomorphic TP53 mutations were present in 21.3% of ovarian cancers in the TCGA dataset. Patients with oncomorphic TP53 mutations demonstrated significantly worse PFS, a 60% higher risk of recurrence (HR=1.60, 95% confidence intervals 1.09, 2.33, p=0.015), and higher rates of platinum resistance (χ(2) test p=0.0024) when compared with single nucleotide mutations not categorized as oncomorphic. Furthermore, tumors containing oncomorphic TP53 mutations displayed unique protein expression profiles, and some mutations conferred increased clonogenic capacity in ovarian cancer cell models. Our study reveals that oncomorphic TP53 mutations are associated with worse patient outcome. These data suggest that future studies should take into consideration the functional consequences of TP53 mutations when determining treatment options.

Topics: Adult; Aged; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Serous; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Humans; Middle Aged; Mutation; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Platinum; Prognosis; Taxoids; Tumor Suppressor Protein p53

To evaluate patterns of relapse in early stage uterine papillary carcinoma (UPSC) patients receiving adjuvant intravaginal radiotherapy (IVRT) with or without chemotherapy.. From 1/1996 to 12/2010, 77 women with stage I-II UPSC underwent surgery followed by IVRT (median 21Gy). Stage IA patients without residual disease at surgery were excluded. IVRT and chemotherapy (carboplatin/taxane) was given to 61 (79%) patients and IVRT alone to 16 (21%). The median follow-up was 62 months for surviving patients.. Of the 77 patients, 11 (14%) relapsed as follows: vaginal 2 (3%), pelvic 5 (6%), para-aortic 5 (6%), peritoneal 6 (8%), and other distant sites 8 (10%). Of the 5 pelvic relapses, 2 were isolated and were salvaged. In those treated without chemotherapy, only 1/16 developed recurrence (mediastinal). The 5-year vaginal, pelvic, para-aortic, peritoneal, and distant recurrence rates were 2.7% (C.I. 0-6.2%), 5.8% (C.I. 0.6-11.0%), 5.4% (C.I. 0.6-10.1%), 5.3% (C.I. 0.5-10.1%) and 6.6% (C.I. 1.4-11.8%), respectively. The 5-year disease-free survival (DFS), and overall survival (OS) were 88% (C.I. 81-95%), and 91% (C.I. 84-97%), respectively. The only predictor of worse 5-year pelvic control was stage (96.2% stage IA vs 87.7% for stage IB-II, p=0.043).. In stage I-II UPSC patients who predominantly receive adjuvant chemotherapy, IVRT as the sole form of adjuvant RT provides excellent locoregional control. The risk of isolated pelvic recurrence is too low to warrant routine use of external pelvic RT.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Bridged-Ring Compounds; Carboplatin; Carcinoma, Papillary; Chemoradiotherapy, Adjuvant; Cystadenocarcinoma, Serous; Disease-Free Survival; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Radiotherapy, Adjuvant; Retrospective Studies; Survival Rate; Taxoids; Treatment Outcome; Uterine Neoplasms

Uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC) represent two rare subtypes that have an increased risk of recurrence and worse overall survival compared with the more common endometrioid endometrial cancers. Meaningful data in the form of prospective randomized trials is lacking for both advanced and early-stage UPSC and UCCC. Data extrapolated from prospective trials in advanced endometrioid endometrial cancer and retrospective trials on early-stage UPSC suggest that adjuvant platinum and taxane-based chemotherapy may provide a survival benefit for these patients. Future trials specifically examining UPSC and UCCC are needed to elucidate the optimal treatment regimen for these patients. Given the current data, the option of chemotherapy should be considered in treatment-planning discussions for all patients with UPSC and UCCC.

Topics: Adenocarcinoma, Clear Cell; Adenocarcinoma, Papillary; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Chemotherapy, Adjuvant; Cystadenocarcinoma, Serous; Endometrial Neoplasms; Female; Humans; Neoplasm Recurrence, Local; Neoplasm Staging; Platinum; Prognosis; Taxoids

The objective of this study was to evaluate the role of an in vitro drug resistance assay to platinum and taxane in the management of advanced epithelial ovarian, fallopian and primary peritoneal cancer. All patients with FIGO Stage IIIc and IV who received postoperative chemotherapy with platinum and taxane for more than 4 courses after the initial cytoreductive surgery between 1995 and 2008 were evaluated. Patients who received neoadjuvant chemotherapy were not included. An in vitro drug resistance assay (EDR Assay, Oncotech, Tustin, CA) was used to determine drug resistance for each patient's tumor tissue. Level of drug resistance was described as extreme (EDR), intermediate (IDR), or low (LDR). Response to chemotherapy and survival were correlated to the EDR Assay. Of the 335 patients who underwent primary cytoreductive surgery, 173 cases met the criteria for statistical evaluation. The 58 patients (33.5%) whose tumors had LDR to both platinum and taxane had statistically improved progression-free survival and overall survival (OS) compared with the 115 patients (66.5%) who demonstrated IDR or EDR to platinum and/or taxane (5-year OS rates, 41.1% vs. 30.9%, p = 0.014). The 5-year OS rates for the 28 (16.2%) cases that had optimal cytoreduction with LDR to both platinum and taxane was significantly improved over the 62 (35.8%) cases that were suboptimally cytoreduced with IDR or EDR to platinum and/or taxane (54.1% vs. 20.4%, respectively, p < 0.001). In conclusion, LDR to both platinum and taxane chemotherapy, as determined by an in vitro drug resistance assay, independently predicts improved survival in patients with advanced epithelial ovarian, fallopian and peritoneal cancer, especially in those patients who undergo optimal primary cytoreduction.

Topics: Adenocarcinoma, Clear Cell; Antineoplastic Combined Chemotherapy Protocols; Biological Assay; Bridged-Ring Compounds; Cystadenocarcinoma, Serous; Drug Resistance, Neoplasm; Endometrial Neoplasms; Fallopian Tube Neoplasms; Female; Humans; In Vitro Techniques; Lymphatic Metastasis; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Survival Rate; Taxoids

Stage I-II uterine papillary serous carcinoma (UPSC) patients have a significant risk for extrapelvic recurrence. However, clinicopathologic risk factors for recurrence are not well understood. This study was undertaken to define the prognostic factors for recurrence and survival in patients with early-stage UPSC.. A retrospective, multi-institution analysis of surgically staged I-II UPSC patients was performed. Patients were treated by various adjuvant modalities. Age, race, sub-stage, percentage UPSC histology, lymphvascular space invasion (LVSI), tumor size and adjuvant treatment modality were evaluated for their effect on recurrence and survival outcomes.. We identified 206 patients. Forty patients (19.4%) had 5-49% UPSC, 55 (26.7%) had 50-99% and 111 patients (53.9%) had 100% UPSC in their respective uterine specimens. Twenty one percent of patients experienced a primary recurrence. On univariate analysis, age, increasing %UPSC, LVSI, and tumor size were not significantly associated with recurrence or progression-free survival (PFS). However, substage (p=0.005) and treatment with platinum/taxane-based chemotherapy (p=0.001) were associated with recurrence/PFS. On multivariate analysis, only chemotherapy (p=0.01) was a significant factor affecting PFS, whereas age (p=0.05), substage (p=0.05), and chemotherapy (p=0.02) were associated with overall survival.. Traditional risk factors for recurrence and survival in patients with early-stage endometrial cancer may not be relevant in patients with UPSC. Patients with any percentage UPSC in their uterine specimens are at a significant risk for recurrence and poor survival outcomes. Given that current clinicopathologic data does not accurately identify women most likely to benefit from adjuvant therapy, alternative prognostic markers based on novel techniques should be explored.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Papillary; Combined Modality Therapy; Cystadenocarcinoma, Serous; Disease-Free Survival; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Retrospective Studies; Taxoids; Uterine Neoplasms

The objective of the present study was to compare recurrence-free survival (RFS) in early stages (FIGO stages I-II) of epithelial ovarian cancer after adjuvant chemotherapy with carboplatin and a taxane (113 patients) and with carboplatin alone (27 patients). The distribution of clinical and pathological prognostic factors as well as type of primary surgery were comparable in the two groups. Recurrence rate was 21% and RFS was 79% in the series of patients treated with taxane-based chemotherapy and 19% and 81%, respectively, in the series of patients who received single drug carboplatin. Thus, no significant differences were recorded. The major toxicities in the present study were myelosuppression (46%) and neuro-toxicity (26%). Neuro-toxicity was more frequently (P=0.007) recorded and of higher grade (P=0.011) for patients in the carboplatin-taxane series compared with patients in the carboplatin series. RFS for patients in FIGO-stage I was 85% and for patients in FIGO-stage II only 47%. In a multivariate logistic regression analysis of predictive factors for tumor recurrence in the complete series (n=140) the FIGO stage was the only independent and significant (P=0.0006) predictive factor with an odds ratio of 6.4 (95% CI: 2.2-18.9) for stage II versus IA-C. Age, tumor grade and type of adjuvant chemotherapy (+/- taxane) were not significant predictive factors. In the present study, although based on a limited number of patients, we could not find any improvement in recurrence rate or recurrence-free survival for patients treated with a carboplatin-taxane combination regimen compared with patients treated with carboplatin monotherapy. The spectrum of side effects was also in favor of the monotherapy regimen. Further, larger randomized studies are needed to give a final and fully conclusive answer to this question.

Topics: Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Carcinoma, Endometrioid; Chemotherapy, Adjuvant; Cystadenocarcinoma, Serous; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Prognosis; Survival Rate; Taxoids

Primary carcinoma of the fallopian tube (PCFT) is a rare malignancy comprising 1% of genital tract cancers. We sought to compare survival trends between PCFT and ovarian carcinoma (OC) patients (pts) in a matched, case-control comparison.. Patients with PCFT were identified from five academic centers. Two OC controls were identified for each PCFT pt based on age, stage, and residual disease. All pts were surgically staged and treated with platinum based chemotherapy (CT) if indicated. PFS and OS were then compared with Kaplan-Meier analysis.. 96 PCFT cases and 189 OC controls were identified. 50 early stage PCFT were matched with 97 OC pts. The most common CT regimen was carboplatinum and paclitaxel in 84 and 86% respectively. Median follow-up was 57 and 42 months for the PCFT and OC groups and 5-year overall survival (OS) differed at 95% and 76% (p=0.02). 46 Stage III/IV PCFT pts were matched with 92 OC controls. 88.5% were optimally debulked. Median follow-up was 33 and 35 months for PCFT and OC pts and 3-year overall survival was 59% for both groups.. This is the first study to compare outcomes for PCFT and OC in a matched, case-control comparison. Our study demonstrates that, for advanced stage PCFT, a similar survival outcome is obtained compared to OC patients. This should reassure clinicians that treatment of PCFT should mirror that of OC and that PCFT should be included in clinical trials.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Case-Control Studies; Chemotherapy, Adjuvant; Cystadenocarcinoma, Serous; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Ovarian Neoplasms; Retrospective Studies; Survival Rate; Taxoids; Treatment Outcome