title: Carboplatin-paclitaxel-induced leukopenia and neuropathy predict progression-free survival in recurrent ovarian cancer.
abstract: BACKGROUND
  We assess the prognostic value of chemotherapy-induced leukopenia and sensory neuropathy in the CALYPSO trial patients treated with carboplatin-paclitaxel (CP) or carboplatin-liposomal doxorubicin (CPLD).
  
  
  METHODS
  We performed a landmark analysis at first month after randomisation to correlate leukopenia (nadir white blood cell <4.0 × 10(9) per litre or severe infection) during cycle 1 of chemotherapy with progression-free survival (PFS). Using time-dependent proportional-hazards models, we also investigated the association between neuropathy and PFS.
  
  
  RESULTS
  Of 608 patients with nadir blood and did not receive growth factors, 72% (CP=70%, CPLD=73%) had leukopenia. Leukopenia was prognostic for PFS in those receiving CP (adjusted hazard ratio (aHR) 0.66, P=0.01). Carboplatin-liposomal doxorubicin was more effective than CP in patients without leukopenia (aHR 0.51, P=0.001), but not those experiencing leukopenia (aHR 0.93, P=0.54; interaction P=0.008).Of 949 patients, 32% (CP=62%, CPLD=28%) reported neuropathy during landmark. Neuropathy was prognostic for PFS in the CP group only (aHR 0.77, P=0.02). Carboplatin-liposomal doxorubicin appeared to be more effective than CP among patients without neuropathy (aHR 0.70, P<0.0001), but not those with neuropathy (aHR 0.96, P=0.81; interaction P=0.15).
  
  
  CONCLUSIONS
  First-cycle leukopenia and neuropathy were prognostic for patients treated with CP. Efficacy of CP treatment was similar to CPLD in patients who developed leukopenia. These findings support further research to understand the mechanisms of treatment-related toxicity.
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Locked Bag 77, Camperdown, NSW 1450, Australia. chee.lee@ctc.usyd.edu.au
authors.forename: C K
authors.initials: CK
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Gurney
authors.forename: C
authors.initials: C
authors.lastname: Brown
authors.forename: R
authors.initials: R
authors.lastname: Sorio
authors.forename: N
authors.initials: N
authors.lastname: Donadello
authors.forename: G
authors.initials: G
authors.lastname: Tulunay
authors.forename: W
authors.initials: W
authors.lastname: Meier
authors.forename: M
authors.initials: M
authors.lastname: Bacon
authors.forename: J
authors.initials: J
authors.lastname: Maenpaa
authors.forename: E
authors.initials: E
authors.lastname: Petru
authors.forename: N
authors.initials: N
authors.lastname: Reed
authors.forename: V
authors.initials: V
authors.lastname: Gebski
authors.forename: E
authors.initials: E
authors.lastname: Pujade-Lauraine
authors.forename: S
authors.initials: S
authors.lastname: Lord
authors.forename: R J
authors.initials: RJ
authors.lastname: Simes
authors.forename: M
authors.initials: M
authors.lastname: Friedlander
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016190:Carboplatin / Q000009:adverse effects*; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced*; D008297:Male; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000009:adverse effects*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011379:Prognosis; D012008:Recurrence
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel