Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in advanced ovarian cancer patients unsuitable for primary surgery: Safety and effectiveness☆
Introduction
Ovarian cancer is the second most common cancer in women with gynecological tumors and the leading cause of mortality among this group of diseases in the USA [1]. It is estimated that 125,000 women die each year worldwide due to this pathology [2], [3]. Approximately 75% of diagnoses are made in advanced stages of the disease (III or IV according to the International Federation of Gynecology and Obstetrics—FIGO) [4]. The recommended treatment for patients with advanced ovarian cancer (FIGO III–IV) is optimal debulking surgery followed by adjuvant chemotherapy based on platinum [4]. Recent studies show similar effects with interval debulking surgery, in which patients are subjected to three cycles of neoadjuvant chemotherapy followed by surgical cytoreduction and three additional cycles of chemotherapy [5].
Optimal cytoreduction is of great importance because the presence of residual disease after surgery was closely related to lower survival rates in a meta-analysis that included 6885 patients with advanced epithelial ovarian cancer (EOC), tubal carcinoma, or primary peritoneal carcinoma (PPC) [6]. In this context, strategies leading to higher rates of complete resection could prolong overall survival or disease-free survival. However, health professionals with expertise in debulking surgery and centers with experience in highly complex cases are needed, particularly for patients with large volume disease.
Interval debulking surgery seems to benefit patients who have large tumor masses that are difficult to remove or low performance status precluding complete resection. The rationale for the use of neoadjuvant chemotherapy is that it: promotes tumor reduction, allowing more effective local treatments with higher rates of optimal cytoreduction; and allows evaluation of the in vivo chemosensitivity of the tumor, avoiding the morbidity of surgery in platinum sensitive patients [8], [9].
Kang et al. conducted a meta-analysis of 21 studies in which overall survival and disease-free survival were similar in patients who underwent primary debulking or interval debulking surgery [9]. In 2010, Vergote et al., in a phase III study (European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada), concluded that interval debulking surgery is not inferior to primary debulking, showing that optimal cytoreduction was more common and that there were fewer postoperative complications in patients undergoing neoadjuvant systemic chemotherapy; no statistically significant differences were found in overall survival or progression-free survival [5]. The optimal duration of preoperative chemotherapy is not defined in the literature. Given this conflicting evidence, our institution treats patients with EOC, tubal carcinoma, or PPC with platinum based neoadjuvant chemotherapy followed by optimal cytoreduction. Extrapolating from the literature, we perform all six cycles of chemotherapy before surgery.
In this retrospective and single institutional study, consecutive EOC, tubal carcinoma, and PPC patients treated with neoadjuvant platinum based systemic chemotherapy (NACT) followed by cytoreductive surgery were evaluated for progression-free survival, overall survival, complications related to surgery, and degree of cytoreduction after neoadjuvant chemotherapy. We aimed to evaluate the safety and efficacy of platinum compounds associated with taxanes in the neoadjuvant treatment of patients with advanced stage cancer of the ovarian epithelium, fallopian tube, or peritoneum. As secondary end points, we evaluated chemotherapy-free survival, overall survival, intraoperative and postoperative complications, and cytoreduction after adjuvant systemic chemotherapy.
Section snippets
Patients
We conducted a retrospective analysis of the medical records of all patients with histologically confirmed locally advanced EOC, tubal carcinoma, or PPC stage III or IV (pleural metastases only, with confirmatory biopsy) who on initial assessment were considered unsuitable for complete (R0) resection due to the extent of their disease. These patients underwent NACT based on platinum and paclitaxel at the Medical Oncology Department of the Instituto do Câncer da Faculdade de Medicina da
Results
Six hundred and fifty-six patients with an ovarian neoplasm were treated at the ICESP-USP between January 2008 and February 2012. Of these, 82 underwent NACT and met the eligibility criteria for the study.
The median age of the patients was 60 years (range 41–82 years). Most were non-smokers (67.1%) and had no family history of cancer (84.1%), 19.5% had never had children, and 73.2% had an ECOG performance status between 0 and 1; 90.2% had serous adenocarcinoma and 78% were in clinical stage IIIC
Discussion
Worldwide, ovarian cancer is the third most common gynecological tumor and the second leading cause of mortality due to such tumors [1]. Treatment is based on optimal surgery and subsequent adjuvant chemotherapy. In advanced stages of the disease it is feasible to perform neoadjuvant therapy followed by interval surgery. The main issue is the ideal time of cytoreductive surgery. This approach remains controversial; the strongest evidence to date is for three cycles of neoadjuvant chemotherapy
Conclusion
We conclude that, in this retrospective study of unselected patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer, treatment with six cycles of platinum-based chemotherapy was safe and effective and did not increase peri- or postoperative comorbidity. The overall survival of our patients was higher than that in studies of similar populations who were treated with interval surgery. This treatment strategy allows more time for planning the surgery, which can be
Conflict of interest statement
The authors declare that there are no conflicts of interest.
Author contributions
Conception and design: Vanessa da Costa Miranda, Maria Del Pilar Estevez Diz, and Carlos Henrique dos Anjos.
Provision of study materials: Vanessa da Costa Miranda, Ângelo Bezerra de Souza Fêde, Carlos Henrique dos Anjos, and Maria Del Pilar Estevez Diz.
Collection and assembly of data: Vanessa da Costa Miranda, Ângelo Bezerra de Souza Fêde, Carlos Henrique dos Anjos, Juliana Ribeiro da Silva, Fernando Barbosa Sanchez, and Lyvia Rodrigues da Silva Bessa.
Data analysis and interpretation: All
References (18)
- et al.
Worldwide burden of gynaecological cancer: the size of the problem
Best Pract Res Clin Obstet Gynaecol
(2006) - et al.
Planning cancer control in Latin America and the Caribbean
Lancet Oncol.
(2013) - et al.
Platinum-based neoadjuvant chemotherapy and interval surgical cytoreduction for advanced ovarian cancer: a meta-analysis
Gynecol Oncol
(2006) - et al.
Secondary surgical cytoreduction for advanced ovarian carcinoma
N Engl J Med
(2004) Site Globocan
- et al.
Global cancer statistics, 2002
CA Cancer J Clin
(2005) - et al.
Staging laparotomy in early ovarian cancer
JAMA
(1983) - et al.
Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer
N Engl J Med
(2010) - et al.
Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis
J Clin Oncol
(2002)
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Funding: None.