Spectrum Pharmaceuticals, Inc., announced that an Investigational New Drug (IND) application was filed with the FDA for the use of SPI-1620 in patients with recurrent or progressive carcinoma. SPI-1620 is being developed as an adjunct to chemotherapy.

SPI-1620 is a highly selective endothelin-B agonist that has demonstrated in experimental models a transient and selective increase in blood flow to tumours by over 300 per cent and consequent increase in delivery of anticancer drugs to the tumour while essentially sparing normal tissues and organs, thereby increasing the efficacy and the therapeutic index of these drugs.

"SPI-1620 has shown preclinical evidence of selectively targeting tumours to increase the uptake of doxorubicin and other anti-cancer agents such as Taxol," said Luigi Lenaz, MD, Chief Scientific Officer of Spectrum Pharmaceuticals. "If proven successful in clinical trials, we believe SPI-1620 could have a broad range of applications as an adjunct to chemotherapy in the treatment of solid tumours. We anticipate starting our Phase 1 trial as soon as we receive clearance from the FDA."

The proposed clinical trial is entitled "A Phase I Open Label, Ascending Dose Study Of The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Endothelin-B Agonist SPI-1620 In Patients With Recurrent Or Progressive Carcinoma."

The American Cancer Society estimates there will be more than 1.4 million new cases of cancer in the U.S. in 2007. Chemotherapy is one of the mainstays of therapy for solid tumours. However, chemotherapy often fails because adequate tissue levels of the cytotoxic agents are not achieved in the tumour and serious side effects result from toxicity to normal cells. Spectrum Pharmaceuticals is developing a novel approach that takes advantage of endothelin biology and the unique angioarchitecture of tumour blood vessels to overcome these problems.

In animal models, SPI-1620 causes selective and transient increase in blood flow to tumours. Increased blood flow in turn leads to an increase in the drug delivery to tumours, which in turn enhances the efficacy of the chemotherapeutic drugs. Proof-of-principle studies have been done in several tumour models, such as breast and prostate tumour models in rats, and melanoma and ovarian tumour models in mice. Increased blood flow in turn led to increase in the delivery of different chemotherapeutic drugs such as paclitaxel, cisplatin, doxorubicin, cyclophosphamide, and 5-FU to tumours. Furthermore, SPI-1620 enhanced the efficacy of chemotherapeutic drugs as demonstrated by improved efficacy of paclitaxel against breast tumours and improved efficacy of cisplatin and cyclophosphamide against ovarian tumours. Similarly SPI-1620 improved the efficacy of doxorubicin and 5-FU in prostate tumour models.