Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy.

Abstract

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.

• Authors: Lajos Pusztai, Tito R Mendoza, James M Reuben, Monica M Martinez, Jie S Willey, Juanita Lara, Abdul Syed, Herbert A Fritsche, Eduardo Bruera, Daniel Booser, Vicente Valero, Banu Arun, Nuhad Ibrahim, Edgardo Rivera, Melanie Royce, Charles S Cleeland, Gabriel N Hortobagyi
• Journal: Cytokine (Cytokine) Vol. 25 Issue 3 Pg. 94-102 (Feb 07 2004) ISSN: 1043-4666 [Print] England
• PMID: 14698135 (Publication Type: Clinical Trial, Comparative Study, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cytokines
• Interleukin-1
• Interleukin-6
• Interleukin-8
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Interleukin-12
• Doxorubicin
• Cyclophosphamide
• Paclitaxel
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Anxiety (chemically induced, diagnosis)
• Blood (drug effects)
• Breast Neoplasms (blood, classification, drug therapy)
• Cyclophosphamide (adverse effects, therapeutic use)
• Cytokines (blood)
• Data Interpretation, Statistical
• Doxorubicin (adverse effects, therapeutic use)
• Fatigue (chemically induced, diagnosis)
• Female
• Fluorouracil (adverse effects, therapeutic use)
• Humans
• Interleukin-1 (blood)
• Interleukin-10 (blood)
• Interleukin-12 (blood)
• Interleukin-6 (blood)
• Interleukin-8 (blood)
• Middle Aged
• Nausea (chemically induced, diagnosis)
• Paclitaxel (administration & dosage, adverse effects, therapeutic use)
• Pain (chemically induced, diagnosis)
• Patient Selection
• Quality of Life
• Tumor Necrosis Factor-alpha (analysis)