PMID- 33756421
OWN - NLM
STAT- MEDLINE
DCOM- 20211025
LR  - 20211025
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 148
DP  - 2021 May
TI  - Reporting the trajectories of adverse events over the entire treatment course in 
      patients with recurrent platinum-sensitive ovarian cancer treated with 
      platinum-based combination chemotherapy regimens: A graphical approach to trial 
      adverse event reporting.
PG  - 251-259
LID - S0959-8049(21)00073-3 [pii]
LID - 10.1016/j.ejca.2021.02.006 [doi]
AB  - BACKGROUND: Clinical trials report adverse events (AEs) in a dense table focusing 
      on the frequency of 'worst grade' AEs experienced over the duration of treatment. 
      There is usually no granular information provided on the timing and trajectory of 
      AEs or whether they are likely to worsen, improve, or remain constant over time. 
      PATIENTS AND METHODS: Non-hematologic (NH) AE data was extracted from the CALYPSO 
      trial comparing carboplatin with pegylated liposomal doxorubicin (CD) to 
      carboplatin with paclitaxel (CP) in recurrent ovarian cancer (ROC). Generalised 
      estimating equations (GEE) were used to assess the risk and trajectory of 
      combined Grade 2 or higher (G2+) AE and of each specific AE. The risk of G2+AE 
      was also compared between treatment arms. RESULTS: The study included 976 
      patients and AE were reported for the duration of treatment. Most patients 
      experienced at least one G2+NHAE (CP:CD, 96.0%:80.6%). Risk of combined G2+AE 
      increased with CP (4.1% per-cycle) but decreased with CD (0.8%, P <0.01). When 
      alopecia and sensory neuropathy were excluded, risk of G2+ AE decreased by 2.7% 
      per-cycle, with no significant difference between treatment arms. G2+ nausea 
      improved (15.2% per-cycle, P <0.01). G2+ sensory neuropathy worsened (29.3% 
      per-cycle, P <0.01). Fatigue was stable (17% per-cycle, P =0.06) whilst G2+ pain 
      decreased over time (13.4% per-cycle, P <0.01), with no difference between 
      treatment arms. CONCLUSION: Existing trial data can be used to provide AE 
      trajectories as illustrated here for ROC. These trajectories have utility in 
      guiding treatment choice and potentially optimising AE management with novel 
      therapies and treatment combinations.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Francis, Katherine E
AU  - Francis KE
AD  - National Health and Medical Research Council Clinical Trials Centre, The 
      University of Sydney, Sydney, NSW, 2050, Australia; Department of Medical 
      Oncology, St George Hospital, Kogarah, NSW, 2217, Australia. Electronic address: 
      katherine.francis@ctc.usyd.edu.au.
FAU - Gebski, Val
AU  - Gebski V
AD  - National Health and Medical Research Council Clinical Trials Centre, The 
      University of Sydney, Sydney, NSW, 2050, Australia.
FAU - Lord, Sarah J
AU  - Lord SJ
AD  - National Health and Medical Research Council Clinical Trials Centre, The 
      University of Sydney, Sydney, NSW, 2050, Australia; School of Medicine, The 
      University of Notre Dame, Sydney, NSW, 2007, Australia.
FAU - Friedlander, Michael
AU  - Friedlander M
AD  - Prince of Wales Clinical School, UNSW and Department of Medical Oncology, Prince 
      of Wales Hospital, Randwick, NSW, 2031, Australia.
FAU - Pujade-Lauraine, Eric
AU  - Pujade-Lauraine E
AD  - Universite Paris Descartes, Paris, France; ARCAGY-GINECO, France.
FAU - Lee, Chee Khoon
AU  - Lee CK
AD  - National Health and Medical Research Council Clinical Trials Centre, The 
      University of Sydney, Sydney, NSW, 2050, Australia; Department of Medical 
      Oncology, St George Hospital, Kogarah, NSW, 2217, Australia.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20210320
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (liposomal doxorubicin)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 80168379AG (Doxorubicin)
RN  - BG3F62OND5 (Carboplatin)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/*adverse effects
MH  - Carboplatin/administration & dosage
MH  - Doxorubicin/administration & dosage/analogs & derivatives
MH  - Drug-Related Side Effects and Adverse Reactions/etiology/*pathology
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Neoplasm Recurrence, Local/*drug therapy/pathology
MH  - Ovarian Neoplasms/*drug therapy/pathology
MH  - Paclitaxel/administration & dosage
MH  - Polyethylene Glycols/administration & dosage
MH  - Prognosis
MH  - Survival Rate
OTO - NOTNLM
OT  - Adverse events
OT  - Chemotherapy
OT  - Ovarian cancer
OT  - Toxicity
COIS- Conflict of interest statement The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2021/03/24 06:00
MHDA- 2021/10/26 06:00
CRDT- 2021/03/23 20:24
PHST- 2020/10/25 00:00 [received]
PHST- 2021/01/19 00:00 [revised]
PHST- 2021/02/02 00:00 [accepted]
PHST- 2021/03/24 06:00 [pubmed]
PHST- 2021/10/26 06:00 [medline]
PHST- 2021/03/23 20:24 [entrez]
AID - S0959-8049(21)00073-3 [pii]
AID - 10.1016/j.ejca.2021.02.006 [doi]
PST - ppublish
SO  - Eur J Cancer. 2021 May;148:251-259. doi: 10.1016/j.ejca.2021.02.006. Epub 2021 
      Mar 20.