Digital Ischemia and Necrosis: A Rarely Described Complication of Gemcitabine in Pancreatic Adenocarcinoma

Abstract

Background: Gemcitabine, alone or in combination with other agents, has become an important part of the standard of care for treatment of both resectable and unresectable/advanced pancreatic adenocarcinoma. Gemcitabine is generally considered to have a favorable toxicity profile, with myelosuppression and hepatotoxicity as the most common adverse effects. There are just two prior published case reports of gemcitabine-associated digital toxicity in the treatment of pancreatic adenocarcinoma, and few case reports when considering all solid tumors.Presentation: A 70-year-old female developed hand numbness and tingling while receiving nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma. There was initial concern for Raynaud's or nab-paclitaxel-associated neuropathy, thus nab-paclitaxel was discontinued. However, her symptoms progressed to severe pain and her digits became dusky. An extensive evaluation revealed no alternative etiology except gemcitabine-associated digital ischemia (DI). The patient was treated with discontinuation of gemcitabine, and starting nitrates, opiates, calcium-channel blockers, and enoxaparin but eventually progressed to dry gangrene.Conclusion: Here we report a case of gemcitabine-associated DI, along with a review of the literature. Although a rare complication, DI must be recognized and treated promptly to reduce the likelihood of serious and permanent morbidity.

Gemcitabine-induced digital ischaemia in a patient with metastatic breast cancer

“…The pathogenesis of gemcitabine’s vascular toxicity is unclear; however, it likely involves endothelial damage, increased platelet activity, activation of the coagulation cascade and immune complex deposition, thereby creating a hypercoagulable state 5 7. The hypercoagulable state from the underlying malignancy, and other risk factors such as smoking, hypercholesterolaemia, peripheral arterial disease and some autoimmune diseases (such as systemic sclerosis) may also contribute to the vascular injury and subsequent thrombosis 8–10. Notably, gemcitabine-induced digital ischaemia in patients with underlying malignancy has been reported in the absence of any additional predisposing risk factors such as was seen in our patient 5.…”

“…In all our reviewed cases, gemcitabine was discontinued at the recognition of ischaemia (see table 1). Antiplatelet agents such as aspirin and anticoagulants including unfractionated or low molecular heparin can be used to prevent thrombosis 5 9 12 13. Topical nitrates, prostaglandin and prostacyclin analogues (such as iloprost), endothelin antagonist (bosentan), and calcium channel blockers have been used for their vasodilatory properties 5 8 9.…”

Progressive digital necrosis during gemcitabine/nab‐paclitaxel chemotherapy in a patient with pancreatic cancer

“…In this previous case, the patient was also receiving gemcitabine/nab-paclitaxel combination therapy (cumulative dose of gemcitabine 4160 mg/m 2 ) for pancreatic cancer, and antinuclear antibody was positive. 2 Another 2 cases of 10 gemcitabine-associated digital ischemia cases showed positive antinuclear antibody. Ischemic change improved after chemotherapy discontinuation in these two cases.…”

“…1 Ten cases of gemcitabine-associated digital ischemia were reported. 2 Possible mechanisms of gemcitabine-induced gangrene are vascular toxicity and endothelial damage. 2 Paclitaxel-induced scleroderma infrequently occurs, but no cases of paclitaxel-induced digital gangrene without sclerodactyly were reported.…”

“…2 Possible mechanisms of gemcitabine-induced gangrene are vascular toxicity and endothelial damage. 2 Paclitaxel-induced scleroderma infrequently occurs, but no cases of paclitaxel-induced digital gangrene without sclerodactyly were reported. 3 In 9 of 10 cases of gemcitabine-associated digital ischemia, ischemic change improved or stopped after chemotherapy discontinuation.…”