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Track 2

DR LOVE: What is your treatment approach for optimally debulked ovarian cancer?

DR MATULONIS: At the Dana-Farber/Harvard Cancer Center, patients with one centimeter or less of residual tumor after surgery either receive standard therapy — carboplatin/paclitaxel or IP cisplatin/paclitaxel — or enroll on a clinical trial.

We are conducting a pilot study evaluating IP carboplatin/paclitaxel with IV bevacizumab in women with newly diagnosed, optimally cytoreduced carcinoma of Müllerian origin. We also have a Phase II trial in which patients receive IV carboplatin/paclitaxel and bevacizumab for six months and then are randomly assigned to receive bevacizumab alone or bevacizumab in combination with erlotinib.

We have data with this combination in other tumors, and we know single-agent erlotinib has minor activity in recurrent ovarian cancer (Gordon 2005). Synergy may exist between these two biologic agents. In addition, high levels of EGFR expression occur in ovarian cancer cells.

We wouldn’t expect erlotinib to do much for a patient with a large-volume recurrence. However, in the maintenance setting for a patient with small-volume disease, some of the anti-angiogenic effects of erlotinib might combine or perhaps synergize with bevacizumab to be beneficial.

Track 6

DR LOVE: How are you using bevacizumab in your practice?

DR MATULONIS: I don’t use bevacizumab for patients with newly diagnosed ovarian cancer, but I do use it in recurrent disease. I select patients carefully and counsel them about the risks. I choose patients with a low risk of gastrointestinal perforation who are not hypertensive. I check their blood pressure and make sure they don’t have any cardiovascular risk factors.

DR LOVE: When the ascites in a patient with refractory, advanced disease responds to bevacizumab, is that an antitumor effect, a vascular effect or both?

DR MATULONIS: When we see a reduction in ascites, we usually see concomitant decreases in peritoneal metastases, lymph node size and the areas of solid tumor growth. Although we can’t be 100 percent certain, I believe it’s an anticancer effect.

Track 9

DR LOVE: What are your thoughts about anti-HER2 therapy in ovarian cancer, including the potential role of pertuzumab?

DR MATULONIS: HER2 is not generally overexpressed in ovarian cancer, so we have to screen many cases to find the few that do overexpress HER2. Even in those patients with HER2 overexpression, the responses to trastuzumab are not particularly robust. Pertuzumab works differently than trastuzumab. Trastuzumab prevents HER2 signaling, while pertuzumab blocks HER2 receptor dimerization with HER3.

Three trials have evaluated pertuzumab in ovarian cancer. A single-agent study was published in the Journal of Clinical Oncology a number of years ago (Gordon 2006). A European Phase II trial evaluated a platinum-based chemotherapy regimen with or without pertuzumab in patients with platinum-sensitive disease (Kaye 2008). Another Phase II trial compared gemcitabine with or without pertuzumab in platinum-resistant ovarian cancer (Makhija 2007; [2.1]).

Track 10

DR LOVE: Can you summarize the efficacy and toxicity associated with IP therapy?

DR MATULONIS: In the GOG-172 trial, comparing IV paclitaxel/cisplatin to IV paclitaxel with IP cisplatin/paclitaxel in patients with Stage III disease, the improvement in overall survival of approximately 16 months in the IP arm was the best we have seen so far (Armstrong 2006; [2.2]). The GOG-111 study, which added IV paclitaxel to IV cisplatin and compared it to IV cisplatin/ cyclophosphamide in patients with Stage III/IV ovarian cancer, reported an approximately one-year improvement in overall survival (McGuire 1996).

The downside of IP therapy is the toxicity, which is greater than that associated with IV regimens, including increased neuropathy, pancytopenia, nausea, vomiting, renal toxicities and electrolyte problems. The side effects are ameliorated somewhat by reducing the cisplatin dose to 75 mg/m², but that dose hasn’t been tested in a randomized manner, so it can’t be recommended uniformly for use.

Track 14

DR LOVE: What is your clinical approach for patients with platinum-refractory ovarian cancer?

DR MATULONIS: Outside of a clinical trial, treatment options include using one of several cytotoxic agents or bevacizumab. I usually choose either topotecan or pegylated liposomal doxorubicin (PLD). I do not use the FDA-approved dose of PLD but a lower dose — 40 mg/m². The lower dose is more tolerable for patients in terms of the rash. Generally, if the rash becomes a problem one can reduce the dose or stretch the interval between cycles. If the rash is Grade II or worse, I generally drop the dose from 40 to 32 mg/m².

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Neil Love, MD

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Tate Thigpen, MD
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Ursula A Matulonis, MD
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Robert A Burger, MD
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Bradley J Monk, MD
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Ovarian Cancer Update:
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