title: Skin toxicities compromise prolonged pemetrexed treatment.
abstract: BACKGROUND
  Pemetrexed is approved to treat non-small cell lung cancer and has an overall favorable toxicity profile. A case of pemetrexed-induced cutaneous adverse events (CAE), i.e., periorbital edema with conjunctivitis and edema of the limbs, leading to severe fluid retention, was diagnosed in our unit. The aim of this study was to evaluate the incidence and risk factors for CAEs.
  
  
  METHODS
  Patients treated with pemetrexed were identified from a prospective cohort. To detect pemetrexed-associated CAEs, questionnaires were answered by patients and the referring oncologist.
  
  
  RESULTS
  Included were 107 patients treated with four cycles or more of pemetrexed. Pemetrexed-induced CAEs were observed in 37 of 107 (35%) total patients (TPs) and 25 of 47 (53%) alive patients (APs). Conjunctivitis was the most frequent CAE: 27 of 107 (25%) in TPs and 21 of 47 (44%) in APs. Periorbital edema occurred in 16 of 107 (15%) TPs and 14 of 47 (30%) APs. Limb edema was present in 14 of 107 (13%) TPs and 12 of 47 (25%) APs. Only two cases of CAE influenced pemetrexed treatment. No significant differences in age, body surface area, smoking status, and performance status were detected. Patients with CAE had more cycles of pemetrexed (7 versus 5.5; p = 0.028). In univariate and multivariate analyses, gender ratio was statistically different (p = 0.031): 48% (12/25) of women in the CAE group versus only 18% (4/18) in the control group.
  
  
  CONCLUSIONS
  Pemetrexed induces frequent conjunctivitis, peripheral edema, and edema of the limbs. Female gender seems to be an independent risk for CAE. CAEs are frequently disabling and symptomatic treatment should be proposed.
authors: Service de Dermatologie, Hôpital Tenon, AP-HP and Faculté de Médecine P&M Curie, Université Paris IV, France.
authors: Belen
authors: B
authors: Eguia
authors: Anne-Marie
authors: AM
authors: Ruppert
authors: Julie
authors: J
authors: Fillon
authors: Armelle
authors: A
authors: Lavolé
authors: Valérie
authors: V
authors: Gounant
authors: Christelle
authors: C
authors: Epaud
authors: Bernard
authors: B
authors: Milleron
authors: Philippe
authors: P
authors: Moguelet
authors: Marie
authors: M
authors: Wislez
authors: Camille
authors: C
authors: Frances
authors: Jacques
authors: J
authors: Cadranel
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003231:Conjunctivitis / Q000139:chemically induced; D003875:Drug Eruptions / Q000209:etiology*; D004487:Edema / Q000139:chemically induced; D005121:Extremities; D005145:Face; D005260:Female; D005971:Glutamates / Q000009:adverse effects* / Q000627:therapeutic use; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000068437:Pemetrexed; D012737:Sex Factors; D011795:Surveys and Questionnaires
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine