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.

    Achieving optimal outcomes in a patient with recurrent ovarian cancer

    Dr. Herman Wong
    Specialist in Medical Oncology
    AmMed Cancer Center

    Presentation and treatment 
    A 63-year-old Chinese female presented with recurrent ovarian cancer (OC) and symptoms of vaginal bleeding, back pain and abdominal distension in August 2012. Physical examination was unremarkable. Cancer antigen 125 (CA-125) level was 1,055 U/mL.(Figure)

    In September 2009, the patient was diagnosed with stage IIIC OC and underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy and anterior resection of the colon. She received six cycles of adjuvant Paclitaxel and Carboplatin.  Six months afterwards, she developed pelvic lymph node and anastomotic recurrence. Liposomal Doxorubicin for six cycles was given but the patient developed intestinal obstruction. Optimal tumor debulking was performed but the procedure was complicated with anastomotic leak. Bypass surgery with colostomy was subsequently performed in April 2011. The patient remained stable for a year without further treatment. In March 2012, she was treated with Topotecan based on biochemical progression but it was discontinued after four cycles as the rise in CA-125 continued unabated. 

    In August 2012, the patient was referred to my service but she declined re-assessment imaging. In view of clinical and biochemical recurrences, combination chemotherapy with Gemcitabine (1,000 mg/m2), Carboplatin (AUC x4) and Bevacizumab (7.5 mg/kg) was commenced. After a week of treatment, clinical response was observed with reduced vaginal bleeding, abdominal pain and distension. Her back pain completely resolved after 2 weeks and the CA-125 decreased to 263 U/mL after one cycle of therapy. (Figure) Grade 1 constipation, malaise and anorexia were reported. The dose of Carboplatin was reduced to AUC x2-3 in subsequent cycles due to grade 2 thrombocytopenia and neutropenia. Vaginal bleeding was not reported after three cycles of treatment and the CA-125 level was normalized to 11.8 U/mL after six cycles of chemotherapy. (Figure) The patient declined imaging for disease monitoring due to financial reasons. 

    Maintenance Bevacizumab was given but the level of tumor marker increased after three cycles of therapy. Gemcitabine and Bevacizumab were administered, however, the CA-125 levels continued to rise. She was subsequently re-challenged with Gemcitabine, Carboplatin and Bevacizumab, resulting in a steady decrease in CA-125 (108 U/mL based on the latest evaluation). (Figure) The patient remains in good condition with this maintenance regimen. 

    Figure. CA-125 levels over the course of chemotherapy plus Bevacizumab treatment in a patient with recurrent ovarian cancer
    DRC ovarian cancer case 8

    The use of Bevacizumab in combination with chemotherapy in the treatment of OC is supported by clinical trial data.1,2 The randomized, double-blind, placebo-controlled phase III Gynecologic Oncology Group (GOG)-0218 trial demonstrated the beneficial use of Bevacizumab for up to 10 months with chemotherapy. There was significantly extended progression-free survival (PFS) compared with chemotherapy plus placebo in patients with advanced epithelial OC (14.1 vs 10.3 months; p<0.001).1 Similarly, the randomized, two-arm, multicenter Gynecologic Cancer InterGroup (GCIG) International Collaboration on Ovarian Neoplasms (ICON7) trial has shown 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).2 

    AURELIA (A Study of Avastin Added to Chemotherapy in Patients With Platinum-resistant Ovarian Cancer), another randomized phase III trial, further demonstrated that chemotherapy plus Bevacizumab conferred significantly improved PFS in patients with platinum-resistant recurrent OC compared with chemotherapy alone (6.7 vs 3.4 months; p<0.001).3 Of particular relevance to this case study, OCEANS (Ovarian Cancer Study Comparing Efficacy and Safety of Chemotherapy and Anti-Angiogenic Therapy in Platinum-Sensitive Recurrent Disease) — a randomized, multicenter, double-blind phase III trial – showed that the addition of Bevacizumab to Carboplatin and Gemcitabine significantly improved PFS compared with the same chemotherapy regimen plus placebo in patients with platinum-sensitive recurrent OC (12.4 vs 8.4 months; p<0.0001).4

    My patient was considered to be platinum-sensitive, though other treatment options are available (eg, rechallenging the patient with Paclitaxel and Carboplatin or using oral Etoposide), the combination of Gemcitabine, Carboplatin and Bevacizumab was chosen because of the simplicity of administration, favorable toxicities and evidence-based survival benefit. According to the patient, this regimen was the most tolerable compared with others she had previously received.

    In summary, this case illustrated the effective use of a Bevacizumab-containing chemotherapeutic regimen in the management of recurrent OC in a heavily-pretreated elderly patient. Good disease control was achieved and the patient was able to enjoy a good quality of life without experiencing significant side effects.   

    1. N Engl J Med 2011;365:2473-2483.
    2. N Engl J Med 2011;365:2484-2496.
    3. J Clin Oncol 2012;30(suppl; abstr LBA5002); 2012 ASCO Annual Meeting.
    4. J Clin Oncol 2012;30:2039-2045.

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