Metastatic Melanoma PV-10 Trial Results Encouraging Says Drug Company
09 Jun 2009

Early results of a clinical trial that treated 40 patients with metastatic melanoma using PV-10, a form of the staining compound better known as Rose Bengal, were described as "encouraging" because the drug was well tolerated and showed selective tumor destruction in the majority of patients, said the drug company developing the treatment.

The early results of the phase 2 trial of its lead oncology treatment were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Orlando, Florida last week by Provectus Pharmaceuticals, Inc, a new development-stage oncology and dermatology biopharmaceutical company based in Knoxville, Tennessee.

The researchers observed a measureable response in lesions treated with PV-10 in 60 per cent of the patients, said Provectus in a statement. The phase 2 trial also confirmed an observed "bystander effect" seen in the phase 1 trial, where untreated lesions also responded, perhaps because the drug stimulated the immune system to attack them.

Principal Investigator for Provectus' Phase 2 PV-10 trial site at St Luke's Hospital & Health Network in Bethlehem, Pennsylvania, Dr Sanjiv Agarwala, who presented the results at the ASCO meeting, said:

"These data provide us much encouragement as they continue to demonstrate how potentially safe and effective PV-10 is for the treatment of metastatic melanoma."

For the trial the researchers recruited 80 patients with Stage III or IV melanoma between late 2007 and May 2009. The patients were at several centers in Australia and the US. The analysis included 35 patients with Stage III and 5 with Stage IV disease who were treated for 2 cycles and a median of 8 lesions each.

The company report said that the "safety and efficacy data demonstrate that therapy with PV-10 compares favorably with available therapeutic options for this patient population".

The trial's key results, as reported by the company, include:
Objective (ie measurable) response of PV-10 treated lesions observed in 60 per cent of patients.

Locoregional disease control of treated lesions was observed in 75 per cent of patients.

Untreated lesions also responded: the so-called "bystander effect", consistent with that seen in the phase 1 trial.

Provisional safety data similar to phase 1, with the most common symptoms being transient mild to moderate locoregional pain, vesicles, edema or swelling.
Explaining the observed "bystander effect" Agarwala said it could be because the drug induced the patients' own immune systems to attack and shrink untreated tumors.

This would be of enormous benefit because melanoma often spreads to areas of the body that are difficult to treat, like the head and the neck.

"The 'bystander effect' could dramatically improve the prognosis for many patients," said Agarwala, saying he and his colleagues were "excited" by the interim results and were looking forward to continuing with the development of the therapy.

Estimates from the American Cancer Society suggest there are 120,000 Americans diagnosed with Stage III or Stage IV melanoma, and 68,000 more new cases will be diagnosed in 2009.

On a global scale, the World Health Organization (WHO) estimates about 48,000 people died of Stage III or Stage IV melanoma in 2008.

Agarwala said that advanced melanoma was very difficult to treat and there have been no new drugs approved in the last ten years.

PV-10 is an injectable form of Rose Bengal developed by Provectus. Rose Bengal is a staining compound that has been used by ophthalmologists and optometrists for about 30 years to assess damage to the eye. It has also been used to diagnose liver problems. The compound has an established safety history, a short half-life and is excreted by the liver and kidneys, said Provectus in a statement.

Rose Bengal kills cancer cells through "chemoablation", a process that mimics both features of necrosis and apoptosis.

"Chemoablation of melanoma with intralesional rose bengal (PV-10)."
J Clin Oncol 27:15s, 2009 (suppl; abstr 9060).
S. S. Agarwala et al
Presented at ASCO 2009 Annual Meeting, on 1 June 2009.