ovarian%20cancer
OVARIAN CANCER
Ovarian cancer is a type of cancer that begins in the ovaries.
It is the 7th most common cancer in women (excluding skin cancer) and the leading cause of death from gynecologic cancer in developed countries.
The 3 histologic types of ovarian cancer are epithelial (primarily seen in women >50 years of age), germ cell (most commonly seen in women <20 years of age) and sex cord stromal (rare and produces steroid hormones).
The median age at the time of diagnosis is 63 years old and >70% present with advanced disease.

    An effective first-line combination chemotherapy for a patient with lymph node metastases from advanced ovarian cancer


    Dr. Wing-Hong Kwan 
    Associate Director, Comprehensive Oncology Center
    Director, Department of Radiotherapy
    Comprehensive Oncology Center
    Hong Kong Sanatorium & Hospital

    Introduction
    Ovarian cancer (OC) is one of the most common causes of cancer related deaths in women worldwide,1 mainly due to its delay in diagnosis. In the past decade, the general standard-of-care for women with advanced OC has been surgery and platinum-based chemotherapy. The most common chemotherapy drugs used as first-line treatment include carboplatin and paclitaxel, which are most often given in combination. In recent years, efforts have been made in introducing novel targeted agents into the treatment armamentarium, with the aim to improve prognosis and quality of life. Bevacizumab, a vascular endothelial growth factor (VEGF)-neutralizing monoclonal antibody, has been approved in the European Union for the first-line treatment of advanced OC in combination with carboplatin and paclitaxel.2 This case report details clinical outcomes in a patient with advanced OC who received Bevacizumab with standard chemotherapy treatment.  

    Presentation and treatment 
    A 55-year-old Chinese female, with no personal history of cancer, presented to a surgeon at our hospital in January 2012 with a swollen (3 cm) partially fixed left supraclavicular lymph node and a small upper left neck node. She did not report any abdominal distension or discomfort and her chest X-ray was unremarkable. Subsequently, an 18F-fluorodeoxyglucose (18F-FDG) PET-CT scan was ordered on 28 January 2012, which revealed active left supraclavicular and upper left neck nodes, lymph nodes over the left paraaortic and portahepatic region, mesenteric and left paracolic gutter nodules, right ovarian mass, liver dome lesion and left pelvic nodule. These findings were radiologically compatible with primary OC with widespread dissemination. A core needle biopsy of the left supraclavicular lymph node was performed, which revealed features of metastatic serous OC. Immunohistochemical staining was positive for CK7 and WT1, confirming the diagnosis of advanced (stage IV) serous epithelial OC.

    On 16 March 2012, the patient was referred to our service and was commenced on six cycles of combination therapy with Paclitaxel (175 mg/m2), Carboplatin (AUC x5) and Bevacizumab (15 mg/kg) every 3 weeks. Prior to treatment, her tumour marker levels were elevated: cancer antigen 125 (CA-125) was 111.2 U/mL; carcinoma antigen 15-3 (CA 15-3) was 70 U/mL; and carcinoembryonic antigen (CEA) was 19.1 U/mL. After four cycles of the Paclitaxel/Carboplatin/Bevacizumab regimen, the patient’s serum levels of CA-125, CA 15-3 and CEA decreased to 14 U/mL, 25 U/mL and 4.1 U/mL, respectively.

    Table. Decreasing serum tumour marker levels indicated that the patient was responding to the Paclitaxel/Carboplatin/Bevacizumab regimen
    DRC ovarian cancer case 2 table  
    CA-125= cancer antigen 125; CA 15-3 = carcinoma antigen 15-3; CEA = carcinoembryonic antigen

    A repeat PET-CT scan was ordered in 30 July 2012, which was negative except for residual metabolic activity detected over the right ovarian region. The left supraclavicular lymph node was also impalpable after Cycle 4 of the treatment. After consulting with a gynaecologist, a laparotomy was performed to detect residual carcinoma and the patient subsequently underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and removal of any suspicious intra-abdominal nodes. Peritoneal washing was also performed and the excised tumours indicated only fibrosis and granulomatous inflammation, with no evidence of residual malignancy. 

    Before the commencement of maintenance treatment with bevacizumab, the patient received postoperative radiation therapy (50 Gy in 25 fractions) for five weeks as a curative measure for the left supraclavicular lymph node. Following that, she treated with maintenance Bevacizumab therapy (15 mg/kg every 3 weeks) from August 2012 to June 2013. She did not report any adverse effects during the 15-month treatment course (ie, the patient had normal blood pressure readings and had no evidence of venous thrombosis, bleeding or proteinuria). The patient is currently in complete pathological remission.

    Discussion
    There have been numerous attempts to improve the standard two-drug chemotherapy for OC by adding a third cytotoxic agent. Given that epithelial OC cell lines frequently express VEGF,3 the addition of Bevacizumab – an angiogenesis inhibitor that binds to all isoforms of the VEGF-receptor ligand, VEGF-A – into chemotherapy and maintenance regimens appears to be a logical treatment strategy for unresectable OC. The use of Bevacizumab in combination with chemotherapy has been shown in clinical trials to improve progression-free survival (PFS) in the treatment of OC.4,5 The randomized, double-blind, placebo-controlled phase 3 Gynecologic Oncology Group (GOG)-0218 trial showed that the use of Bevacizumab for up to 10 months with chemotherapy significantly extended PFS compared with chemotherapy plus placebo in patients with advanced epithelial OC (14.1 vs 10.3 months; p<0.001).4 In a similar vein, the randomized, two-arm, multicentre Gynecologic Cancer InterGroup (GCIG) International Collaboration on Ovarian Neoplasms (ICON7) trial demonstrated that, in patients at high risk for OC progression, the addition of Bevacizumab to standard chemotherapy significantly prolonged PFS (16.0 vs 10.5 months; p=0.002) and median overall survival (36.6 vs 28.8 months; p=0.002).5

    Our patient, who presented with neither comorbidities nor abdominal symptoms characteristic of advanced OC, achieved remarkably good disease control on the Paclitaxel/Carboplatin/Bevacizumab regimen. While OCs tend to be fairly chemoresponsive initially, maintaining or prolonging the duration of disease control is often challenging. In this regard, Bevacizumab was chosen for maintenance therapy due to its relatively long-term clinical efficacy, as shown in the GOG-0218 trial. Moreover, the patient exhibited good tolerance to the 15-month Bevacizumab therapy. 

    In summary, this case illustrates the effective use of a Bevacizumab-containing chemotherapeutic regimen in the management of advanced epithelial OC with lymph node metastasis. Complete remission was achieved and the patient was able to enjoy an improved quality of life post-treatment. 

    References:
    1. Centers for Disease Control and Prevention. Ovarian Cancer Statistics: http://www.cdc.gov/cancer/ovarian/statistics/. 
    2. Avastin® (bevacizumab) [summary of product characteristics]. European Medicines Agency (EMA); 2012.
    3. J Natl Cancer Inst 1998;90:447-54.
    4. N Engl J Med 2011;365:2473-2483.
    5. N Engl J Med 2011;365:2484-2496.

    This special report is made possible through an unrestricted educational grant from the industry and first appeared in MIMS Oncology.
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