Amrubicin for the treatment of small cell lung cancer: does effectiveness cross the Pacific?

Amrubicin is a synthetic 9-aminoanthracycline that has significant antitumor activity in Japanese patients with extensive stage small cell lung cancer (SCLC). Clinical trials ongoing in the United States and Europe will determine whether amrubicin will be effective in other ethnic groups (whites) or whether this will be an example of geographic and/or genetic variation. Genetic polymorphisms in the UGT1A1 gene have been identified as one of the causes of the increased diarrhea seen in white patients treated with irinotecan when compared with Japanese patients. Nicotinamide adenine dinucleotide phosphate, reduced form-quinone oxidoreductase (NQ01) is an enzyme that participates in the metabolism of amrubicin and polymorphisms of the enzyme, known to occur in the Asian population, might explain the effectiveness of the drug in Japanese patients with small cell lung cancer. Studies to evaluate the drug in US and European patients with extensive stage small cell lung cancer are ongoing. Levels of NQ01 will also be determined in these studies.