Spectrum Pharmaceuticals Presents Data on SPI-1620, a Novel Adjunct to Chemotherapy, at the American Association of Cancer Research Meeting

IRVINE, Calif., Apr 15, 2008 (BUSINESS WIRE) -- Spectrum Pharmaceuticals, Inc., (Nasdaq:SPPI) announced that data on a field study with SPI-1620 in dogs with spontaneously occurring tumors were presented via poster presentation at the 2008 Annual Meeting of the American Association of Cancer Research (AACR), held in San Diego, California. SPI-1620, a highly selective endothelin-B receptor agonist, is being developed as an adjunct to cancer therapy. In earlier preclinical studies, SPI-1620 had demonstrated evidence of transiently enhancing the blood flow to tumors, thus increasing the delivery and efficacy of chemotherapeutic agents to tumors, sparing normal tissues.

"In an ongoing field study with tumor-bearing dogs, being conducted at the University of Missouri- Columbia, SPI-1620 thus far has demonstrated evidence of selectively and transiently increasing blood flow to spontaneously-occurring tumors," said Rajesh C. Shrotriya, M.D., Chairman, President and Chief Executive Officer of Spectrum Pharmaceuticals, Inc. "This dog study is a more predictive study than transplanted tumors in rodents. In previous rodent model studies we have demonstrated that SPI-1620 enhances the efficacy of a wide variety of chemotherapeutics in different tumor models. We believe that SPI-1620, currently in a Phase 1 clinical trial, could have a broad range of applications for use in conjunction with radiation and chemotherapy in the treatment of cancer."

#365 Use of a Novel Endothelin-B Agonist (SPI-1620) To Alter Blood Flow to Solid Tumors for Improved Chemotherapy Delivery in Dogs with Spontaneously-Occurring Tumors

Tumor-bearing dogs were enrolled in a field study and evaluated via physical examination and hematologic assessment. SPI-1620 was injected intravenously over one minute, and then laser Doppler probes (Periflux 4000(R: 67.12, +3.05, +4.76%), Perimed AB, Sweden) were used to measure perfusion in tumor and distant normal tissue for 3 hours. Cohorts of three dogs per dosage level were treated starting at 0.2 ug/kg. On day 7, SPI-1620 treatment was repeated followed 15 minutes later by chemotherapy. Toxicity monitoring included clinical observation and hematologic assessment.

To date, 5 dogs have been treated (3 at 0.2ug/kg and 2 at 0.4ug/kg) without toxicity. All vital signs have remained normal during and after each treatment for all dogs. All blood parameters have remained normal until after treatment for all dogs. Tumor perfusion increased 38-94% starting 17-20 minutes after SPI-1620 injection, with maximum effect by 1 hour and lasting for 3 hours post-injection. Perfusion to normal tissue changed less than 15%. One dog with metastatic mast cell tumor experienced a partial response. Enrollment in escalating dosage cohorts is ongoing.

It was concluded that SPI-1620 appears to affect blood flow to solid tumors and is well tolerated. This may improve delivery of chemotherapy to tumors and warrants further investigation of the effect on drug delivery and efficacy.

About SPI-1620

According to the most recent American Cancer Society estimates, in the United States, approximately 1.4 million new cancer cases were expected to be diagnosed in 2008 and over 565,000 persons were expected to die from the disease in 2008. Cancer is the second most common cause of death in the United States. Chemotherapy is one of the mainstays of therapy for solid tumors. However, chemotherapy often fails because adequate tissue levels of the cytotoxic agents are not achieved in the tumor and serious side effects result from toxicity to normal cells. Consequently, any means to increase the delivery of a cytotoxic agent selectively to tumors, while minimizing its concentration in normal tissues, would be beneficial.

SPI-1620 is a highly selective endothelin-B agonist that causes a selective and transient increase in blood flow to tumors, thereby, as demonstrated in preclinical studies, increasing the delivery of anticancer agents to the tumor, and as a result increasing the efficacy of these drugs. In these pre-clinical studies, when anti-cancer drugs, such as paclitaxel, doxorubicin, cisplatin, 5-FU, cyclophosphamide and others, were administered shortly after SPI-1620, the anti-cancer drug concentration in the tumor increased several fold. This resulted in increased anti-tumor efficacy at a given dose of the cytotoxic agent, and thus might allow physicians to maximize efficacy of reduced cytotoxic agent doses with resultant decreased toxicity to the normal organs. Preclinical proof of principle studies have been successfully conducted in a wide variety of indications such as breast, ovarian, melanoma, and prostate cancer. SPI-1620 is currently in a Phase 1 trial that is an open label, dose-escalation study assessing the safety, tolerability, pharmacokinetics and pharmacodynamics of SPI-1620 in patients with recurrent or progressive carcinoma.

Spectrum has proprietary worldwide rights to SPI-1620.

About Spectrum Pharmaceuticals