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Dr. Jack West is a medical oncologist and thoracic oncology specialist, and Executive Director of Employer Services at the City of Hope Comprehensive Cancer Center in Duarte, CA.

Picoplatin for SCLC: A New Platinum for Salvage Therapy?
Fri, 02/08/2008 - 23:07
Author
Howard (Jack) West, MD, Associate Clinical Professor, Medical Oncology, Executive Director, Employer Services, Founder, President and CEO of GRACE

Member Wendy asked me about a drug called picoplatin that I had heard of but really didn't have much familiarity with. This gave me an occasion to flesh out some background on this agent, which is being developed as a potential therapy for patients previously treated for lung cancer. Developed by Poniard Pharmaceuticals in South San Francisco, picoplatin is a variant platinum drug, which cause cell death by binding to DNA and interfering with its ability to make copies and divide, which in turn leads to programmed cell death (a self-destruct program), also known as apoptosis. It was designed to have a slightly different shape from cisplatin or carboplatin that would make it overcome resistance to these other platinum drugs, and early studies suggest that it has some activity in platinum-pretreated patients, and also a lower risk for kidney damage and neuropathy that can accompany platinum use, particularly cisplatin.

Picoplatin image

(Click on image to enlarge)

Early work in lung cancer (abstract here) demonstrated that responses were obtainable in platinum-treated patients with SCLC, with response rates in of 8% in patinum-sensitive patients and 15% in platinum-resistant patients (defined by whether patients experienced recurrence at least 3 months after last chemo, or in less time than that).

Picoplatin generated more attention last year, when results of a phase II trial in previously treated SCLC patients was reported at ASCO (abstract here) and then the World Conference on Lung Cancer in Korea (abstract here). This study included 77 patients, most of whom with either progression before the end of first-line chemo or within three months of completing it. Although there is an oral formulation of picoplatin, this study administered the drug as an IV infusion over 1-2 hours every three weeks. Importantly, it was well tolerated, with no grade 3 or 4 neurotoxicity, and side effects mostly low blood counts, but not especially low. There were no treatment-related deaths. While the response rate was only 10%, there was clearly activity in previously treated patients; another 38% had stable disease. Below is a "waterfall plot" below, which graphs increases or decreases in tumor volume relative to a horizontal line representing no change (and with patient outcomes going from worst (upward = growth) to best (downward = shrinkage) from left to right. The waterfall plot indicates that while responses may have been only 10%, but a much larger percentage, approaching half, had some degree of tumor shrinkage:

Picoplatin waterfall curve

picoplatin curves

The median progression-free survival of 10 weeks and median overall survival of 27 weeks were also fairly favorable compared to topotecan and supportive care (see prior post), if not as impressive as amrubicin in phase II Japanese trials in this same setting (see prior post).

Based on these results, the company is running a phase III randomized trial called SPEAR, for Study of Picoplatin Efficacy After Relapse), which will enroll about 400 previously treated and now relapsed SCLC patients from Eastern Europe and India. Participants will be randomized in a two to one fashion to receive active drug along with supportive care, or best supportive care alone, and it will be looking for a significant improvement in overall survival:

SPEAR logo

SPEAR schema

The trial has just recently gotten off the ground but is moving along well, with enrollment projected to end several months from now, and earliest results to beome available even perhaps by the end of this year. There's more information on the trial here.

While the response rates in the 50% range with amrubicin in phase II trials have piqued the interest of many of us in the field more than a 10% response rate with picoplatin could, I think it's important to recognize that we're seeing that different racial groups can have very different responses to treatment and overall behaviors of a cancer. Results in Japan may actually be very different from what we'd see in North America or Europe, so comparisons may be apples and oranges. With the difficulty we've had making advances in SCLC, any drug that has proven responses in previously treated patients is worthy of study as a potential new option and advance in the field.

More as the story develops.

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