Gemcitabine-Related Pneumonitis in Pancreas Adenocarcinoma—An Infrequent Event: Elucidation of Risk Factors and Management Implications

Abstract

A total of 2440 pancreatic cancer patients who received gemcitabine treatment were screened for gemcitabine-related pneumonitis (GRP). The observed rate of GRP was 1.1%. History of smoking, alcohol use, and history of underlying lung disease were identified as possible risk factors of GRP. Early pulmonary consult and cessation of gemcitabine is recommended once clinical suspicion arises. Background Gemcitabine-related pneumonitis (GRP) has been reported relatively frequently for pancreas cancer in the literature; however, underlying risk factors and optimal management remain to be defined. We studied a cohort of patients with GRP and investigated potential predisposing factors in pancreatic cancer patients. Patients and Methods A total 2440 patients at Memorial Sloan Kettering Cancer Center were identified between January 1, 2000, and December 31, 2012, and were screened for grade 2 or higher GRP in an institutional tumor registry and using an ICD billing code database. Demographic and clinical information was extracted by electronic chart review. Results A total of 28 patients (1.1%) with GRP were identified. Incidence of grade 2, 3, and 4 reactions were 7 (25%), 18 (64%), and 3 (11%), respectively. No GRP-related mortality was observed. Twenty-one patients (75%) reported a history of cigarette smoking. Seventeen patients (61%) were alcohol users. Six patients (21%) were either regular or heavy drinkers. Most patients (93%) had either locally advanced or metastatic disease. Three patients (11%) underwent a diagnostic bronchoscopy, and in 1 patient a diagnosis of organizing pneumonia was established. Morbidity was significant; 3 patients (11%) required treatment in the intensive care unit. All hospitalized patients received steroid treatment. Conclusion GRP is relatively uncommon but incurs significant morbidity. Potential risk factors include advanced-stage disease, along with smoking and alcohol consumption and possibly underlying lung disease. We recommend a high level of clinical alertness regarding the diagnosis, early pulmonary referral, and cessation of gemcitabine on suspicion of GRP.

Drug-Induced Interstitial Lung Disease: A Systematic Review

“…Gemcitabine is used to treat a range of cancers, including non-small cell lung cancer (NSCLC), pancreatic cancer and breast cancer [ 13 , 25 , 26 , 27 , 28 ]. The risk of DIILD is highest when used in combination with other agents, especially bleomycin, erlotinib and taxanes [ 25 , 26 , 28 , 29 , 30 , 31 ], with reported incidence rates of 1–20%. Mortality rates are generally low [ 26 , 27 , 28 , 32 ] except in severe cases requiring hospitalisation, where mortality reaches 20% [ 30 ].…”

“…The risk of DIILD is highest when used in combination with other agents, especially bleomycin, erlotinib and taxanes [ 25 , 26 , 28 , 29 , 30 , 31 ], with reported incidence rates of 1–20%. Mortality rates are generally low [ 26 , 27 , 28 , 32 ] except in severe cases requiring hospitalisation, where mortality reaches 20% [ 30 ]. In contrast to bleomycin, the dose relationship and timing of onset are less consistent [ 13 , 26 , 29 ].…”

“…Mortality rates are generally low [ 26 , 27 , 28 , 32 ] except in severe cases requiring hospitalisation, where mortality reaches 20% [ 30 ]. In contrast to bleomycin, the dose relationship and timing of onset are less consistent [ 13 , 26 , 29 ].…”

Phase 1b study of a small molecule antagonist of human chemokine (C-C motif) receptor 2 (PF-04136309) in combination with nab-paclitaxel/gemcitabine in first-line treatment of metastatic pancreatic ductal adenocarcinoma

“…An observed rate of pneumonitis in patients treated with gemcitabine was approximately 1% and was elevated up to 4% when combined with nab-paclitaxel [3], leading to a high level of morbidity. Furthermore, advanced-stage disease, smoking, and alcohol consumption, and possibly underlying lung disease, can be potential risk factors of gemcitabine-related pneumonitis [28]. Infections, in particular, are frequent complications in patients with malignancies.…”

PD-1/PD-L1 antibodies efficacy and safety versus docetaxel monotherapy in advanced NSCLC patients after first-line treatment option: systems assessment

“…Although, anti-PD-1 drugs rarely caused pneumonitis (any grade 4-6%, grade 3-4: 0-2%), but pneumonitis has significant potential for morbidity and mortality, and thus, occurence of it should be approached with caution. Similar to fatal pneumonitis, interstitial lung disease (ILD) have also been represented in advanced NSCLC patients treated with EGFR-TKIs (gefıtinib: 3.5%; erlotinib: about 1.6%-4.5%) [ 43 , 44 ] and with chemotherapy (docetaxel: 4.6%; gemcitabine: < 1%) [ 45 – 47 ]. In recent years, there has been reports about docetaxel-related interstitial lung disease (ILD), where ILD onset occurred 10-20 days (median time: 18 days) after docetaxel administration [ 48 , 49 ].…”