Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report

Radiation recall phenomenon is now a well-recognized phenomenon since radiation recall dermatitis was reported in 1975 [4]. Radiation recall dermatitis has been reported most frequently with a frequency of 8.8 % and characterized by an inflammatory reaction within a previously irradiated skin after administration of antineoplatic drugs [5].

Antineoplastic drugs have mainly been involved in radiation recall reactions. Most common anticancer agents that cause radiation recall reactions are the anthracycline doxorubicin, the taxanes docetaxel and paclitaxel, and the antimetabolites gemcitabine and capecitabine [1].

Although there are several pathophysiological theories concerning radiation recall, the most accepted hypothesis is the drug hypersensitivity reaction. In this hypothesis, radiation lowers the inflammatory response threshold and induces the expression of certain cytokines, and then the drug triggers a non-immune inflammatory reaction [1].

Gemcitabine induced radiation recall was reported in the skin, central nervous system, musculoskeletal systems and gastrointestinal tract. The time between initiation of radiation and recall of the radiation phenomenon ranged from 3 weeks to 8 months from the initiation of gemcitabine [6].

Dermatitis and pneumonitis were reported as the radiation recall reactions associated with erlotinib [7]. Recently there was a report of gastrointestinal bleeding secondary to radiation recall gastritis related to erlotinib [3]. The mechanism of erlotinib-induced radiation recall gastritis is also unclear, but Graziani et al. [3] suggested the association between the pathogenesis of radiation recall and erlotinib’s up-regulation of the angiogenic growth factor thymidine phosphorylase. Erlotinib, as an orally administered epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, can cause gastrointestinal ulcer without relation with radiation because EGFR is highly expressed in the epithelium of the gastrointestinal tract. However, this case showed ulcers and prominent wall thickening only in gastric antrum and body, confined to previously irradiated area. To our knowledge, this report is the first case of radiation recall gastritis due to combination of gemcitabine and erlotinib. It could be assumed that the combination therapy could result in a higher radiation recall incidence.

Radiation recall reactions have been reported in the literature, but management remains controversial whether or not to continue the drug, especially chemotherapeutic agent. Suggested management of the recall reaction is discontinuing drug and initiating steroid therapy, supportive therapy, and/or nonsteroidal anti-inflammatory agents [6]. There were two reports treated with discontinuing drug in radiation gastritis associated with gemcitabine and erlotinib [2, 3]. Meanwhile there is a partial support for the continuation of chemotherapy even when a recall reaction is encountered [8]. In this case, diffuse gastritis and ulcers were treated with PPI and the patient eventually recovered from the radiation recall gastritis without discontinuation of chemotherapy. It can be assumed that recovery was partly due to reduced absorption of erlotinib because absorption of erlotinib is known to be pH dependent. However Ter Heine et al. [9] reported that trough concentrations of erlotinib were not diminished when PPI was administered orally. More studies are needed on the role of PPI in radiation gastritis.