Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy.
BACKGROUND
Flu-like symptoms are common, early transient side effects of paclitaxel chemotherapy. We hypothesized that these symptoms may be due to release of inflammatory cytokines in response to treatment. The objective of this study was to assess changes in plasma levels of interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12, and TNF-alpha during chemotherapy and to correlate these changes with musculoskeletal symptoms.


METHODS
Ninety patients with breast cancer were included; 70 patients received single agent paclitaxel either weekly or every 3 weeks and 20 received FAC (5-FU, doxorubicin, cyclophosphamide) chemotherapy. Fifteen healthy volunteers were included as controls. Cytokines and symptoms were measured before starting therapy, on day 3 and on the last day of one treatment cycle.


RESULTS
At baseline, all subjects had measurable levels of IL-8 but only 49% had IL-12, 45% had IL-10, 32% had IL-6, and 21% had IL-1beta or TNF-alpha in their plasma. There was no difference in baseline cytokine levels between cancer patients and the healthy volunteers. Schedule-dependent transient changes in the levels of 3 cytokines were observed in the paclitaxel treated patients. In the every 3-week paclitaxel group, IL-6 and IL-8 increased whereas in the weekly paclitaxel group IL-10 increased significantly compared to baseline. Fatigue and flu-like symptoms were also worse on day 3. In the weekly paclitaxel group, increase in IL-10 level correlated positively with joint pain (p=0.003). In the every 3-week paclitaxel group, increase in IL-8 level correlated positively with flu-like symptom (p=0.008). In the FAC-treated group and among the healthy volunteers none of these cytokines increased significantly.


CONCLUSIONS
Weekly paclitaxel induces transient increase in IL-10 levels whereas every 3-week higher dose treatments induce IL-8 and IL-6 in the plasma. These changes correlate with joint pain and flu-like symptoms.
Pusztai
Lajos
L
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. lpusztai@mdanderson.org
Mendoza
Tito R
TR
Reuben
James M
JM
Martinez
Monica M
MM
Willey
Jie S
JS
Lara
Juanita
J
Syed
Abdul
A
Fritsche
Herbert A
HA
Bruera
Eduardo
E
Booser
Daniel
D
Valero
Vicente
V
Arun
Banu
B
Ibrahim
Nuhad
N
Rivera
Edgardo
E
Royce
Melanie
M
Cleeland
Charles S
CS
Hortobagyi
Gabriel N
GN
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001007:Anxiety / Q000139:chemically induced / Q000175:diagnosis; D001769:Blood / Q000187:drug effects; D001943:Breast Neoplasms / Q000097:blood / Q000145:classification / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood*; D003627:Data Interpretation, Statistical; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005221:Fatigue / Q000139:chemically induced / Q000175:diagnosis; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000175:diagnosis; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010146:Pain / Q000139:chemically induced / Q000175:diagnosis; D018579:Patient Selection; D011788:Quality of Life; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000970:Antineoplastic Agents; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil