title: Correlation of toxicity and efficacy with pharmacokinetics (PK) of pegylated liposomal doxorubicin (PLD) (Caelyx®).
abstract: OBJECTIVE
  Pegylated liposomal doxorubicin (PLD) is used to treat patients with breast and gynecological cancers. In order to optimize treatment with PLD, we assessed the prognostic and predictive factors for efficacy of PLD.
  
  
  METHODS
  Seventeen patients treated with PLD 30 or 40 mg/m(2) underwent pharmacokinetic sampling during the first cycle of treatment. PLD exposure was calculated. An univariate analysis was performed with the variables: hand-foot syndrome, mucositis, rash, neutropenia, age, tumor type, number of previous therapies, ECOG performance status and progression-free survival (PFS). Candidate variables with p ≤ 0.1 were selected for the multivariate analysis.
  
  
  RESULTS
  Based on the results of the multivariate analysis, the PLD exposure (log AUC) was higher in patients who experienced rash (p = 0.002) and mucositis (p = 0.001) compared to those who did not have these adverse events. The development of hand-foot syndrome was significantly related to a lower risk of disease progression (HR 0.1; 95 % CI 0.02-0.64). Patients with an ECOG status of 0 had a longer PFS than the patients with an ECOG status of 1 (HR 5.4; 95 % CI 1.3-22.8). Moreover, PLD exposure (ln AUC) was also positively related to PFS (HR 0.001; 95 % CI 0.00-0.42).
  
  
  CONCLUSIONS
  The extent of the exposure to PLD was correlated with more adverse events and longer PFS. This has important clinical implications, since dose reductions or interruptions might thus negatively affect treatment outcomes. More attention should be paid to preventive and supportive measures of adverse events of PLD to keep the exposure to PLD as high as possible.
authors: Department of Medical Oncology, 452, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands, Marye.Boers-Sonderen@radboudumc.nl.
authors: Marye J
authors: MJ
authors: Boers-Sonderen
authors: Carla M L
authors: CM
authors: van Herpen
authors: Winette T A
authors: WT
authors: van der Graaf
authors: Ingrid M E
authors: IM
authors: Desar
authors: Mirjam G W Arens-
authors: MG
authors: van der Logt
authors: Yvo M
authors: YM
authors: de Beer
authors: Petronella B
authors: PB
authors: Ottevanger
authors: Nielka P
authors: NP
authors: van Erp
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D060831:Hand-Foot Syndrome / Q000209:etiology; D006801:Humans; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000493:pharmacokinetics; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; C401859:temsirolimus; D004317:Doxorubicin; D020123:Sirolimus