title: Erlotinib pharmacokinetics: a critical parameter influencing acute toxicity in elderly patients over 75 years-old.
abstract: Background Older non-small cell lung cancer (NSCLC) patients under erlotinib are reported to experience more acute toxicity. We hypothesized that modifications in erlotinib pharmacokinetics might explain this observation. Methods A monocentric prospective clinico-pharmacological study included stage IIIb/IV NSCLC consecutive pts. treated with erlotinib. The plasma concentration of erlotinib (Ce) was measured at steady state on day 15. We studied the relationship between age > 75 years, and Ce, using the Mann-Whitney U test and with the occurrence of acute toxicity, using a Fisher's test. Results A total of 53 pts. were analyzed. Median age was 68 years (31-83), 56 % were female. All pts. > 75 years experienced toxicity: all grade acute adverse events were 1.6 fold more frequent (100 % vs 61 %; OR 95 % CI [1.9-INF]; p = 0.003). At day 15, Ce increased with age. Over 75 years old, the mean Ce was 1.5 fold higher: 2091 ng/mL (95 % CI [1476; 2706]) vs 1359 (95 % CI [1029; 1689]; p = 0.024). In pts. over 80 years old, the mean Ce was doubled: 2729 (95 % CI [1961; 3497]) vs 1358 ng/mL (95 % CI [1070; 1646]; p = 0.0019). Reduced lean body mass over 75 years (median 36.6 kg versus 49.1 kg) might account for these differences. Finally, the risk of early erlotinib discontinuation was increased by 11 in older pts. (33 % vs 3 % OR 17.2; 95 % CI [1.7; 892.5] p = .005). Conclusion The risk of overexposure to erlotinib increases with age. Reduced lean body mass may explain erlotinib pharmacokinetics and excessive acute toxicity in the elderly.
authors: Department of Medical Oncology, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Sorbonne Paris Cité 123, Boulevard de Port-Royal, 75014, Paris, France.
authors: Frederic
authors: F
authors: Bigot
authors: Department of Medical Oncology, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Sorbonne Paris Cité 123, Boulevard de Port-Royal, 75014, Paris, France. pascaline.boudou@aphp.fr.
authors: Pascaline
authors: P
authors: Boudou-Rouquette
authors: Department of Medical Oncology, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Sorbonne Paris Cité 123, Boulevard de Port-Royal, 75014, Paris, France.
authors: Jennifer
authors: J
authors: Arrondeau
authors: Department of Medical Oncology, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Sorbonne Paris Cité 123, Boulevard de Port-Royal, 75014, Paris, France.|UF Pharmacocinétique et pharmacochimie, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Paris, France.|UMR 8638 CNRS, Faculty of Pharmacy of Paris, Université Paris Descartes, SPC, Paris, France.
authors: Audrey
authors: A
authors: Thomas-Schoemann
authors: Department of Medical Oncology, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Sorbonne Paris Cité 123, Boulevard de Port-Royal, 75014, Paris, France.
authors: Camille
authors: C
authors: Tlemsani
authors: Department of Medical Oncology, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Sorbonne Paris Cité 123, Boulevard de Port-Royal, 75014, Paris, France.|Department of Pneumology, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Paris, France.
authors: Jeanne
authors: J
authors: Chapron
authors: Department of Medical Oncology, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Sorbonne Paris Cité 123, Boulevard de Port-Royal, 75014, Paris, France.
authors: Olivier
authors: O
authors: Huillard
authors: Department of Medical Oncology, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Sorbonne Paris Cité 123, Boulevard de Port-Royal, 75014, Paris, France.
authors: Anatole
authors: A
authors: Cessot
authors: Department of Medical Oncology, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Sorbonne Paris Cité 123, Boulevard de Port-Royal, 75014, Paris, France.|UF Pharmacocinétique et pharmacochimie, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Paris, France.|UMR 8638 CNRS, Faculty of Pharmacy of Paris, Université Paris Descartes, SPC, Paris, France.
authors: Michel
authors: M
authors: Vidal
authors: Department of Medical Oncology, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Sorbonne Paris Cité 123, Boulevard de Port-Royal, 75014, Paris, France.
authors: Jerome
authors: J
authors: Alexandre
authors: Department of Medical Oncology, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Sorbonne Paris Cité 123, Boulevard de Port-Royal, 75014, Paris, France.|UF Pharmacocinétique et pharmacochimie, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Paris, France.
authors: Benoit
authors: B
authors: Blanchet
authors: Department of Medical Oncology, Cochin - Port Royal Hospital, AP-HP, Paris Descartes University, Sorbonne Paris Cité 123, Boulevard de Port-Royal, 75014, Paris, France.
authors: Francois
authors: F
authors: Goldwasser
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001827:Body Height; D015992:Body Mass Index; D001835:Body Weight; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000069347:Erlotinib Hydrochloride
keywords: Elderly; Erlotinib; Pharmacokinetic; Plasma monitoring; Toxicity