Neoadjuvant chemotherapy (NACT) is an effective way of managing elderly women with advanced stage ovarian cancer (FIGO Stage IIIC and IV).
ABSTRACT BACKGROUND: To compare outcomes in women ≥ age 70 who receive neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer (EOC) followed by cytoreductive surgery with those undergoing upfront cytoreductive surgery followed by the same chemotherapy. METHODS: A retrospective cohort study was performed for women ≥ age 70 with Stage IIIC or Stage IV EOC from 1996 to 2009. RESULTS: Sixty-two patients who underwent upfront cytoreductive surgery and 42 patients who received NACT were eligible for analysis. Patients receiving NACT were significantly more likely to have Stage IV disease (P = 0.004). Cytoreduction to no macroscopic disease was achieved in 71.4% of women who received NACT and 28.1% of women undergoing upfront surgery (P < 0.001). NACT patients had significantly less blood loss at surgery (P = 0.01), required fewer small bowel resections (P = 0.009), had shorter ICU stays (P = 0.02) and fewer hospital days (P = 0.04). NACT patients experienced a trend toward an improved progression-free survival (P = 0.078); however, no statistically significant differences were found in either the progression-free or overall survival analyses. CONCLUSION: NACT is associated with reduced perioperative morbidity in elderly patients with advanced stage ovarian cancer. J. Surg. Oncol © 2012 Wiley Periodicals, Inc.
- SourceAvailable from: Hiroaki Itamochi[Show abstract] [Hide abstract]
ABSTRACT: Approximately 70% of women with epithelial ovarian cancer (EOC) are diagnosed with advanced stage disease, which is associated with high morbidity and mortality. The standard approach to treating patients with advanced EOC remains primary debulking surgery (PDS) followed by chemotherapy. EOC is one of the most sensitive of all solid tumors to cytotoxic drugs, with over 80% of women showing a response to standard chemotherapy combined with taxane and platinum. Furthermore, residual disease is a major prognostic factor for survival. On the basis of the clinical features, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is considered to be an alternative treatment option to standard treatment in patients unable to undergo complete resection during PDS. Noninferiority of NACT-IDS to PDS has been demonstrated in some randomized controlled trials and meta-analyses. NACT would also lead to improved quality of life (QOL) of patients, however there are still problems to be solved in the treatment strategy. The uncertainty of perioperative visual assessment of tumor dissemination after NACT has been reported. In addition, several papers have shown the possibility that NACT induces platinum resistance. Furthermore, a notable risk associated with NACT is that patients with significant side effects and refractory disease will lose the opportunity for debulking surgery. Appropriate selection of the patient cohort for NACT is an important issue. Bevacizumab (Bev) is active in patients with advanced EOC. However, the use of Bev is not recommended in the neoadjuvant setting. Bev has a specific adverse event profile that needs to be considered, especially for surgical management, such as gastrointestinal perforation, hemorrhage, and thromboembolic events. NACT could be an alternative treatment option in patients with stage III or IV EOC. However, further studies are needed to clarify the precise role of NACT in the management of advanced EOC.Therapeutic Advances in Medical Oncology. 11/2014; 6(6):293-304.
- [Show abstract] [Hide abstract]
ABSTRACT: Critics have suggested that neoadjuvant chemotherapy (NACT) followed by interval debulking may select for resistant clones or cancer stem cells when compared to primary cytoreduction. β-tubulins are chemotherapeutic targets of taxanes and epothilones. Class III β-tubulin overexpression has been linked to chemoresistance and hypoxia. Herein, we describe changes in class III β-tubulin in patients with advanced ovarian carcinoma in response to NACT, in relationship to clinical outcome, and between patients who underwent NACT versus primary debulking; we characterize in vitro chemosensitivity to paclitaxel/patupilone of cell lines established from this patient population, and class III β-tubulin expression following repeated exposure to paclitaxel. Using immunohistochemistry, we observed among 22 paired specimens obtained before/after NACT decreased expression of class III β-tubulin following therapy within stroma (p = 0.07), but not tumor (p = 0.63). Poor median overall survival was predicted by high levels of class III β-tubulin in both tumor (HR 3.66 [1.11,12.05], p = 0.03) and stroma (HR 4.53 [1.28,16.1], p = 0.02). Class III β-tubulin expression by quantitative-real-time-polymerase-chain-reaction was higher among patients who received NACT (n = 12) compared to primary cytoreduction (n = 14) (mean ± SD fold-change: 491.2 ± 115.9 vs. 224.1 ± 55.66, p = 0.037). In vitro subculture with paclitaxel resulted in class III β-tubulin upregulation, however, cell lines that overexpressed class III β-tubulin remained sensitive to patupilone. Overexpression of class III β-tubulin in patients dispositioned to NACT may thus identify an intrinsically aggressive phenotype, and predict poor overall survival and paclitaxel resistance. Decreases in stromal expression may represent normalization of the tumor microenvironment following therapy. Epothilones warrant study for patients who have received neoadjuvant carboplatin and paclitaxel.Clinical and Experimental Metastasis 09/2013; · 3.46 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: In Denmark, the proportion of women with ovarian cancer treated with neoadjuvant chemotherapy (NACT) has increased, and the use of NACT varies among center hospitals. We aimed to evaluate the impact of first-line treatment on surgical outcome and median overall survival (MOS). All patients treated in Danish referral centers with stage IIIC or IV epithelial ovarian cancer from January 2005 to October 2011 were included. Data were obtained from the Danish Gynecological Cancer Database, the Danish National Patient Register and medical records. Of the 1,677 eligible patients, 990 (59%) were treated with primary debulking surgery (PDS), 515 (31%) with NACT, and 172 (10%) received palliative treatment. Of the patients referred to NACT, 335 (65%) received interval debulking surgery (IDS). Patients treated with NACT-IDS had shorter operation times, less blood loss, less extensive surgery, fewer intraoperative complications and a lower frequency of residual tumor (p<0.05 for all). No difference in MOS was found between patients treated with PDS (31.9 months) and patients treated with NACT-IDS (29.4 months), p=0.099. Patients without residual tumor after surgery had better MOS when treated with PDS compared with NACT-IDS (55.5 and 36.7 months, respectively, p=0.002). In a multivariate analysis, NACT-IDS was associated with increased risk of death after two years of follow-up (HR=1.81 CI:1.39-2.35). No difference in MOS was observed between PDS and NACT-IDS. However, patients without residual tumor had superior MOS when treated with PDS, and NACT-IDS could be associated with increased risk of death after two years of follow-up.Gynecologic Oncology 12/2013; · 3.93 Impact Factor