Gemcitabine and radiotherapy: Analysis of safe use

Abstract

18146 Background: Radiation in combination with chemotherapy offers a significant survival advantage. Preclinical and clinical data indicate that gemcitabine (GEM) is a potent radiosensitizing agent in numerous cancer types used subsequently with radiation given in different doses and techniques. We compared safety/toxic effects of GEM with GEM plus radiation. Methods: Lilly Safety Database was searched for all reports where patients received radiation before, during and after GEM therapy. The string search for ‘radio’, ‘radia’ and a search for MedDRA terms covering possible radiation recall and typical recall phenomena were conducted. Cases were reviewed by a physician and allocated to one of the categories: ‘concurrent’ (radiation and GEM was given at the same time or 7 days apart), and ‘non-concurrent’ (treatment was given more than 7 days apart). Results: In one third of cases who received concurrent treatment the toxicity reported was higher in 3 System Organ Classes (SOC): ‘Injury’, ‘Gastrointestinal disorders’ (GI), and ‘Respiratory’ in comparison to non radiation treated patients: 4.1%, 16%, 14.8% versus 1.4%, 11.2% and 10.5% respectively but toxicity was lower for ‘Blood and lymphatic disorders’ and ‘General disorders’. In cases with ‘non-concurrent’ treatment the results were similar to ‘concurrent’ treatment for the Injury, Respiratory and Blood SOCs but GI toxicity was only 60% of the one seen in non radiation treated patients. In patients with reported radiation recall the most frequent were skin reactions, pneumonitis and myositis. Radiation injury mainly affected targeted tissue organs exposed to direct radiation e.g eosophagitis and pneumonitis for chest irradiation, GI effects for abdominal irradiation. In Non-concurrent administration no correlation between GEM dose and toxicity could be established. In Concurrent cases, treatment dose and technique of radiation, target tissue and volume were factors together with dose and frequency of GEM administration. Conclusions: Review of adverse drug reactions for GEM and radiation treatment reported from estimated GEM exposure of nearly 1.1 million patients suggests that any increase in GEM toxicity in non- concurrent combination regimen other than radiation recall is due to typical radiation toxicity and mainly affects directly irradiated tissues. No significant financial relationships to disclose.