Do Not Give Up
Most women with advanced ovarian cancer undergo cytoreductive surgery and chemotherapy, enter a period of follow-up, and ultimately relapse. Although there are a number of therapeutic interventions in this situation with at least 7 active chemotherapy or biological agents and the possibility of secondary cytoreductive surgery, long-term survival after relapse is rare and most women succumb to their disease.1
We present a woman diagnosed with an advanced ovarian cancer who had a total of 22 relapses, 19 systemic treatments, and 6 localized palliative interventions for over a 14-year period, which, to the best of our knowledge, to more therapy than has been described before. She had no previous significant medical history but did have a positive family history of ovarian cancer; her sister died from the disease at the age of 48 years and a paternal cousin developed ovarian cancer in her 60s. On the basis of this, she elected to undergo prophylactic oophorectomies at the age of 46 years but imaging before surgery revealed an ovarian mass, which led to a pelvic clearance and omentectomy, and she was diagnosed with a stage 3 grade 3 endometrioid carcinoma of the ovary. After surgery, she had adjuvant chemotherapy in the context of the SCOTROC3 study.2 She relapsed 7 months later rendering her only partially platinum sensitive. Despite this, she went on to receive platinum-containing chemotherapy on 10 separate occasions, and each time, this resulted in a Ca125 marker and clinical response (Fig. 1). In between and during most treatments, she was fit and enjoyed a good quality of life.
Interestingly, genetic screening on the basis of her family history and her repeated responses to platinum-based chemotherapy did not reveal a BRCA mutation when initially performed around the time of diagnosis or when repeated several years later with the assumption that improved molecular techniques would identify a mutation. It is quite possible, however, that she will have had an as yet unidentified mutation conferring “BRCAness” that may have responded to Poly (ADP-ribose) polymerase inhibitors. Drugs used (Table 1) in combination with platinum in her case include etoposide, paclitaxel, and gemcitabine. Drugs used as single agents included oral altretamine, pegylated liposomal doxorubicin, oral cyclophosphamide, and tamoxifen. Nodal relapses were treated with palliative radiotherapy to good effect and she participated in 4 different clinical trials. Her first relapse was 7 months after primary treatment and most of her subsequent treatment free intervals were between 4 and 6 months except after 2 clinical trials involving vascular disruptive agents (VDAs) where the intervals were much longer (18 months for combretastatin3 and 9 months after OXI45034). The monoclonal antibody, bevacizumab, and other antiangiogenic agents have been investigated and have a role in the treatment of ovarian cancer, but this is 1 class of drugs to which she was not exposed. The funding approval for bevacizumab in the United Kingdom was in the first-line5 and platinum-sensitive6 settings and did not apply to this patient. It had been hoped that she would remain well enough to enter another VDA trial in combination with pazopanib, an antiangiogenic tyrosine kinase inhibitor (PAZOFOS, UKCRN 88145142), but sadly she died before the study opened.
This case demonstrates that platinum resistance by conventional definition does not mean that patients with ovarian cancer will never respond to platinum in the future and the role of VDAs, alongside conventional antiangiogenics in the management of this disease, is looked to with interest.