Incidence and management of mTOR inhibitor-associated pneumonitis in patients with metastatic renal cell carcinoma.
The administration of mammalian target of rapamycin (mTOR) inhibitors can give rise to a potentially life-threatening adverse event, often referred to as 'non-infectious pneumonitis' (NIP), which is characterized by non-infectious, non-malignant, and non-specific inflammatory infiltrates. Patients usually present with cough and/or dyspnoea. We provide a brief description of the mechanism of action of mTOR inhibitors and their overall safety in patients with metastatic renal cell carcinoma (mRCC) and review the literature on mTOR inhibitor-associated NIP in patients with solid tumours. The review was used to derive questions on the diagnosis, management, and monitoring of mRCC patients with NIP, and to develop a decision tree for use in routine clinical practise. A key recommendation was the subdivision of grade 2 NIP into grades 2a and 2b, where grade 2a is closer to grade 1 and grade 2b to grade 3. This subdivision is important because it takes into account the nature and severity of clinical symptoms potentially related to NIP, either the onset of new symptoms or the worsening of existing symptoms, and thus determines the type and frequency of follow-up. It also helps to identify a subgroup of patients in whom treatment, if effective, may be continued without dose adjustment.
Department of Medical Oncology, Institut Gustave-Roussy, Villejuif. Electronic address: laurence.albiges@igr.fr.
L
L
Albiges
Department of Radiology, Hôpital Européen Georges Pompidou, Paris.
F
F
Chamming's
Department of Medical Oncology, Strasbourg University Hospital.
B
B
Duclos
Department of Pulmonary Medicine, Hôpital Foch, Suresnes, France.
M
M
Stern
Department of Medicine, Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, USA.
R J
RJ
Motzer
Department of Medical Oncology, Bordeaux University Hospital, Hôpital Saint-André, Bordeaux.
A
A
Ravaud
Department of Pulmonary Medicine and Critical Care, Dijon University Hospital, Hôpital du Bocage, Dijon, France.
P
P
Camus
D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009362:Neoplasm Metastasis; D011014:Pneumonia / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases