Carboplatin-paclitaxel-induced leukopenia and neuropathy predict progression-free survival in recurrent ovarian cancer

C. K. Lee, H. Gurney, C. Brown, R. Sorio, N. Donadello, G. Tulunay, W. Meier, M. Bacon, J. Maenpaa, E. Petru, N. Reed, V. Gebski, E. Pujade-Lauraine, S. Lord, R. J. Simes, M. Friedlander

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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% (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.

LanguageEnglish
Pages360-365
Number of pages6
JournalBritish Journal of Cancer
Volume105
Issue number3
DOIs
Publication statusPublished - 26 Jul 2011
Externally publishedYes

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Carboplatin
Leukopenia
Paclitaxel
Ovarian Neoplasms
Disease-Free Survival
Drug Therapy
Random Allocation
Proportional Hazards Models
Intercellular Signaling Peptides and Proteins
Leukocytes

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Lee, C. K. ; Gurney, H. ; Brown, C. ; Sorio, R. ; Donadello, N. ; Tulunay, G. ; Meier, W. ; Bacon, M. ; Maenpaa, J. ; Petru, E. ; Reed, N. ; Gebski, V. ; Pujade-Lauraine, E. ; Lord, S. ; Simes, R. J. ; Friedlander, M. / Carboplatin-paclitaxel-induced leukopenia and neuropathy predict progression-free survival in recurrent ovarian cancer. In: British Journal of Cancer. 2011 ; Vol. 105, No. 3. pp. 360-365.
@article{83909e14367143ef83ad3b8fc4624515,
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{\%} (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.",
author = "Lee, {C. K.} and H. Gurney and C. Brown and R. Sorio and N. Donadello and G. Tulunay and W. Meier and M. Bacon and J. Maenpaa and E. Petru and N. Reed and V. Gebski and E. Pujade-Lauraine and S. Lord and Simes, {R. J.} and M. Friedlander",
year = "2011",
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Lee, CK, Gurney, H, Brown, C, Sorio, R, Donadello, N, Tulunay, G, Meier, W, Bacon, M, Maenpaa, J, Petru, E, Reed, N, Gebski, V, Pujade-Lauraine, E, Lord, S, Simes, RJ & Friedlander, M 2011, 'Carboplatin-paclitaxel-induced leukopenia and neuropathy predict progression-free survival in recurrent ovarian cancer', British Journal of Cancer, vol. 105, no. 3, pp. 360-365. https://doi.org/10.1038/bjc.2011.256

Carboplatin-paclitaxel-induced leukopenia and neuropathy predict progression-free survival in recurrent ovarian cancer. / Lee, C. K.; Gurney, H.; Brown, C.; Sorio, R.; Donadello, N.; Tulunay, G.; Meier, W.; Bacon, M.; Maenpaa, J.; Petru, E.; Reed, N.; Gebski, V.; Pujade-Lauraine, E.; Lord, S.; Simes, R. J.; Friedlander, M.

In: British Journal of Cancer, Vol. 105, No. 3, 26.07.2011, p. 360-365.

Research output: Contribution to journalArticleResearchpeer-review

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.

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U2 - 10.1038/bjc.2011.256

DO - 10.1038/bjc.2011.256

M3 - Article

VL - 105

SP - 360

EP - 365

JO - British Journal of Cancer

T2 - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 3

ER -