Paclitaxel for anthracycline-resistant AIDS-related Kaposi's sarcoma: clinical and angiogenic correlations.
BACKGROUND
Murine data indicate that angiogenesis is central to the aetiopathogenesis of Kaposi's sarcoma (KS). Therefore, we measured angiogenic cytokines and growth factors in patients with AIDS-related KS during treatment with both antiretrovirals and second-line paclitaxel chemotherapy. Cytokines measured included tumour necrosis factor-alpha (TNF-alpha), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and the interleukins IL-2, -6 and -12.


METHODS
Enzyme-linked immunosorbent assays (ELISAs) were carried out to measure plasma cytokine levels in 17 patients with AIDS-related KS who had progressed within 6 months of receiving liposomal anthracyclines and were treated with paclitaxel 100 mg/m(2) every 2 weeks. Measurements were carried out before progression, at commencement and at the completion of paclitaxel.


RESULTS
The objective response rate to paclitaxel was 71% (95% confidence interval 60% to 81%). In 17 patients with AIDS-related KS, we observed eight partial responses and four complete responses. Patients with AIDS Clinical Trial Group stage T1 disease had higher plasma VEGF (P = 0.05) and lower plasma TNF-alpha levels (P = 0.05) than patients with earlier stage T0 KS. There were no correlations between plasma cytokines (bFGF, VEGF, TNF-alpha, and IL-2,-6 and -12) and the CD4 and CD8 cell counts or HIV-1 RNA viral load. Response to paclitaxel was associated with a fall in plasma IL-6 levels (P = 0.04) but no change in other cytokines. There were no significant changes in CD4, CD8, CD16/56, CD19 cell counts and HIV-1 viral loads during chemotherapy.


CONCLUSIONS
Angiogenic cytokines may correlate with KS disease extent but not with cellular immune function or HIV viraemia. Response to paclitaxel therapy correlates with a fall in plasma IL-6 levels and recent data indicate this may be a surrogate marker of KS-associated herpesvirus viral load. Overall, clinical response in KS correlates poorly with known angiogenic cytokines.
Departments of Oncology and HIV Medicine, Chelsea and Westminster Hospital, London, UK.
J
J
Stebbing
A
A
Wildfire
S
S
Portsmouth
T
T
Powles
C
C
Thirlwell
P
P
Hewitt
M
M
Nelson
S
S
Patterson
S
S
Mandalia
F
F
Gotch
B G
BG
Gazzard
M
M
Bower
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000188:drug therapy; D000328:Adult; D018943:Anthracyclines / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D014408:Biomarkers, Tumor / Q000097:blood*; D018450:Disease Progression; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D012514:Sarcoma, Kaposi / Q000098:blood supply / Q000188:drug therapy* / Q000821:virology; D012878:Skin Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000821:virology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D018943:Anthracyclines; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D017239:Paclitaxel