Favorable response to anti-VEGF therapy and chemotherapy in platinum-sensitive recurrent ovarian cancer
Dr. Roger KC Ngan
Consultant Clinical Oncologist
Department of Clinical Oncology
Queen Elizabeth Hospital
History and presentation
Ms. X is a 44-year-old lady who presented in 2009 with stage IIc clear cell carcinoma of the ovary with histology-proven peritoneal deposits over the pelvic peritoneum and sigmoid colon surface and cytology-positive ascitic fluid. After staging laparotomy and tumor debulking surgery, no macroscopic residual tumor was left behind. She was planned for six cycles of Paclitaxel and Carboplatin. However, she developed facial flushing and lip swelling after 10 minutes of Paclitaxel infusion despite standard premedications, and further Paclitaxel chemotherapy was withheld. The patient was instead switched to Carboplatin and Cyclophosphamide chemotherapy for six cycles. Due to significant neutropenia and neutropenic sepsis, both dose reduction and delays were necessary, and the six cycles of chemotherapy lasted from September 2009 to June 2010.
She presented with hemoptysis in July 2012, 2 years from the end of chemotherapy.
Cancer antigen 125 (CA 125) was normal. Chest X-ray and PET-CT showed a solitary 4.5 cm tumor in the left upper lobe of the lung, for which a lobectomy was performed. Pathology confirmed metastatic clear cell carcinoma.
The pros and cons of starting salvage chemotherapy for microscopic distant metastases were discussed, and the patient opted for observation. Her serum CA 125 was elevated in April 2013 (about 9 months from the lung operation), and CT scan showed widespread recurrences in the abdomen with multiple sizeable peritoneal deposits in the diaphragmatic and liver surface, left paracolic gutter, and left pelvic cavity. (Figures 1A, 2A, 3A, 4A) There was no enlarged lymphadenopathy or thoracic recurrence.
Treatment and follow-up
After thorough discussion, Ms. X was started on Gemcitabine (1,000 mg/m2, days 1 and 8), Carboplatin (AUC=5, day 8, prescribed at 80 percent dose levels due to prior poor marrow tolerance 2-3 years ago), and Bevacizumab (15 mg/kg, day 1 of 3-weekly cycles). Despite growth factor support and pre-emptive dose reduction, there were conceivable dose delays in the 2nd and 3rd cycles with cycle duration prolonged from 3 weeks to about 5 weeks. Fortunately, no neutropenic fever or sepsis has been encountered so far. No significant adverse events related to Bevacizumab were observed after the three cycles of combined chemotherapy and bevacizumab. An interim CT scan performed after the 2nd cycle of chemotherapy and Bevacizumab confirmed significant regression of the lesions.
(Figures 1B, 2B, 3B, 4B) Significant interval regression of the peritoneal deposits in the subphrenic space, left paracolic gutter and pelvic cavity was observed. (Figures 1 to 4) The plan is to continue the chemotherapy/Bevacizumab regimen for at least six cycles and then re-evaluate. Without evidence of disease progression or significant adverse reaction, maintenance Bevacizumab will be planned and continued.
This case shows that significant objective radiological response can be observed after very brief chemotherapy plus Bevacizumab in a patient with platinum-sensitive relapsed ovarian cancer, despite suboptimal dose intensity of chemotherapy.
In the OCEANS study (Ovarian Cancer Study Comparing Efficacy and Safety of Chemotherapy and Anti-Angiogenic Therapy in Platinum-Sensitive Recurrent Disease), patients with platinum-sensitive relapsed ovarian cancer had favorable progression-free survival (PFS) and objective response rate (ORR) when treated with Gemcitabine/Carboplatin chemotherapy together with Bevacizumab vs chemotherapy alone (median PFS extended for 4 months and ORR increased by 21 percent), although overall survival benefit was not observed.1 In the study, Bevacizumab was allowed to be withheld for a maximum of 6 weeks and would be discontinued beyond a period of suspension of more than 6 weeks. However, continuation of Bevacizumab was allowed even though a component of the chemotherapy regimen was discontinued.
Ms. X had difficulty in catching up with the planned schedule of the chemotherapy/Bevacizumab regimen despite chemotherapy dose reduction and pre-emptive growth factor support. This was probably more related to her intrinsic poor marrow tolerance demonstrated 2 years ago during adjuvant Cyclophosphamide/Carboplatin chemotherapy.
There was no excessive neutropenia or neutropenic sepsis in the Bevacizumab arm in the OCEANS study.1 Despite the suboptimal dose intensity of the first two cycles, our patient achieved a very impressive response in the peritoneal lesions.
1. 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.