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Expert Discusses Docetaxel's Continued Significance in Prostate Cancer

Danielle Bucco
Published: Wednesday, Jan 11, 2017

William Oh, MD

William Oh, MD

Although targeted therapies and immunotherapy are revolutionizing oncology, chemotherapy retains a key role in the treatment of advanced prostate cancer, with recent data showing profound benefits with docetaxel in newly diagnosed patients, according to William Oh, MD.

The recent positive findings seen with docetaxel come from 2 randomized trials: CHAARTED and STAMPEDE. In the larger STAMPEDE trial (2962 patients), adding docetaxel to standard hormonal therapy significantly improved survival among men with newly diagnosed, hormone-naïve advanced prostate cancer. The median overall survival (OS) was 81 months with docetaxel plus standard of care (hormonal therapy with or without radiotherapy) versus 71 months with standard of care alone (0.78; 95% CI, 0.66-0·93; P = .006). In the CHAARTED study (790 patients), the median OS was 57.6 months with the combination of docetaxel and androgen-deprivation therapy (ADT) versus 44 months with ADT alone (HR, 0.61; 95% CI, 0.47-0.80; P <.001).

According to Oh, these results are particularly interesting because docetaxel has already been available for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) for over a decade. He added that there were multiple negative trials involving combining another agent with docetaxel in mCRPC, which preceded the surprising discovery that the addition of the drug early on led to such benefits.

In an interview with OncLive at the 2016 Chemotherapy Foundation Symposium, Oh, chief, Division of Hematology and Medical Oncology, professor of Medicine and Urology, Mount Sinai School of Medicine, discussed the continued significance of docetaxel in advanced prostate cancer.

OncLive: Can you provide an overview of the role of docetaxel in metastatic prostate cancer?

Oh: The role of docetaxel in hormone sensitive metastatic prostate cancer is probably one of the biggest new advances in the last 2 years, based on 2 large randomized trials: CHAARTED from the United States and STAMPEDE from the United Kingdom.

While everyone else in other cancers is looking at targeted therapies and immunotherapy, unfortunately, we’re still in the era of chemotherapy; however, the reason we’re in the era of chemotherapy is that docetaxel has a profound effect when used in newly diagnosed metastatic hormone sensitive prostate cancer.

In both studies the survival benefit was quite dramatic, ranging from up to 20 months of benefit in terms of the added benefit of chemotherapy in the group receiving docetaxel early. It’s 6 cycles of docetaxel given without prednisone within 4 months or so of the initiation of ADT for metastatic prostate cancer.

Were you surprised by the results?

This was an interesting result because docetaxel, as everyone knows, has been approved for mCRPC for over a decade, and we have been using it in our practice and it has value in the setting for CRPC. Unfortunately, we were never able to enhance that effect in CRPC; in other words, there have been multiple negative clinical trials adding another drug to docetaxel in CRPC.

This was a bit of a surprise when we found that docetaxel had so much added benefit when used early, and it makes some sense because obviously, we know that there are high-risk metastatic patients who have clones that are going to be resistant to primary hormonal therapy and by using early chemotherapy, we seem to be pushing off the cancer. We’re not curing any of these patients, but we are basically delaying progression enough that there is a significant survival benefit.

How has tolerability been with docetaxel in your patients?

Tolerability is very, very important because this is an older group of men. The traditional approach would be ADT alone, which men don’t like but they can tolerate and live sometimes for many years with this treatment. Adding about 4 and a half months of treatment with docetaxel chemotherapy is not a trivial matter.

Now that said, the toxicity in general was very reasonable, and I have been using this now for the past 2 and a half years in my own practice, and I found that it is difficult in some patients but it is mostly neutropenia, fatigue, some fluid retention. These are side effects that we have understood to be related to docetaxel for many years, so I have made adjustments.

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