TY - JOUR
T1 - Carboplatin-paclitaxel-induced leukopenia and neuropathy predict progression-free survival in recurrent ovarian cancer
AU - Lee, C. K.
AU - Gurney, H.
AU - Brown, C.
AU - Sorio, R.
AU - Donadello, N.
AU - Tulunay, G.
AU - Meier, W.
AU - Bacon, M.
AU - Maenpaa, J.
AU - Petru, E.
AU - Reed, N.
AU - Gebski, V.
AU - Pujade-Lauraine, E.
AU - Lord, S.
AU - Simes, R. J.
AU - Friedlander, M.
PY - 2011/7/26
Y1 - 2011/7/26
N2 - 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% (CP70%, CPLD73%) had leukopenia. Leukopenia was prognostic for PFS in those receiving CP (adjusted hazard ratio (aHR) 0.66, P0.01). Carboplatin-liposomal doxorubicin was more effective than CP in patients without leukopenia (aHR 0.51, P0.001), but not those experiencing leukopenia (aHR 0.93, P0.54; interaction P0.008).Of 949 patients, 32% (CP62%, CPLD28%) reported neuropathy during landmark. Neuropathy was prognostic for PFS in the CP group only (aHR 0.77, P0.02). Carboplatin-liposomal doxorubicin appeared to be more effective than CP among patients without neuropathy (aHR 0.70, P0.0001), but not those with neuropathy (aHR 0.96, P0.81; interaction P0.15). Conclusion: 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.
AB - 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% (CP70%, CPLD73%) had leukopenia. Leukopenia was prognostic for PFS in those receiving CP (adjusted hazard ratio (aHR) 0.66, P0.01). Carboplatin-liposomal doxorubicin was more effective than CP in patients without leukopenia (aHR 0.51, P0.001), but not those experiencing leukopenia (aHR 0.93, P0.54; interaction P0.008).Of 949 patients, 32% (CP62%, CPLD28%) reported neuropathy during landmark. Neuropathy was prognostic for PFS in the CP group only (aHR 0.77, P0.02). Carboplatin-liposomal doxorubicin appeared to be more effective than CP among patients without neuropathy (aHR 0.70, P0.0001), but not those with neuropathy (aHR 0.96, P0.81; interaction P0.15). Conclusion: 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.
UR - http://www.scopus.com/inward/record.url?scp=79960847018&partnerID=8YFLogxK
U2 - 10.1038/bjc.2011.256
DO - 10.1038/bjc.2011.256
M3 - Article
C2 - 21750553
AN - SCOPUS:79960847018
SN - 0007-0920
VL - 105
SP - 360
EP - 365
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 3
ER -