ABSTRACT
WHAT IS KNOWN AND OBJECTIVE: Human herpesvirus-8 (HHV-8)-positive, HIV-negative multicentric Castleman's disease is a rare lymphoproliferative disorder with no standardized treatment. Concurrent Kaposi's sarcoma, another HHV-8-related disease, is uncommon in HIV-negative patients. The role of antiviral therapy and rituximab in HIV-negative patients is not well established. CASE DESCRIPTION: We report a case of a 5-year, durable remission of HHV-8-positive, HIV-negative comorbid multicentric Castleman's disease and Kaposi's sarcoma treated with long-term valganciclovir, following initial rituximab and liposomal doxorubicin. WHAT IS NEW AND CONCLUSION: Currently, there is no defined role for antiviral therapy in the treatment of HIV-negative HHV-8-positive multicentric Castleman's disease and Kaposi's sarcoma. Ganciclovir followed by indefinite, continuous valganciclovir is thought to have contributed significantly to the durable response in this case.
Subject(s)
Antineoplastic Agents/therapeutic use , Castleman Disease/drug therapy , Doxorubicin/analogs & derivatives , Ganciclovir/analogs & derivatives , Rituximab/therapeutic use , Sarcoma, Kaposi/drug therapy , Antiviral Agents/therapeutic use , Castleman Disease/virology , Doxorubicin/therapeutic use , Ganciclovir/therapeutic use , HIV Infections/drug therapy , Herpesviridae Infections/drug therapy , Humans , Male , Middle Aged , Polyethylene Glycols/therapeutic use , Sarcoma, Kaposi/virology , ValganciclovirABSTRACT
BACKGROUND: Bevacizumab prolongs progression-free survival (PFS) in patients with metastatic colorectal cancer. We analysed the protein expression levels of vascular endothelial growth factor (VEGF) ligands and receptors to determine their prognostic and predictive effects. METHODS: We graded expression of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, and VEGF-R2 to assess whether overexpression predicted bevacizumab resistance in samples from 268 of 471 patients randomised to capecitabine (C), capecitabine and bevacizumab (CB), or CB and mitomycin (CBM) in the MAX trial and extended the analysis to the CAIRO-2 population. RESULTS: Patients with low expression of VEGF-D (0, 1þ) benefited from bevacizumab treatment (PFS hazard ratio (HR) (C vs CBþCBM), 0.21; 95% CI, 0.080.55; overall survival (OS) HR, 0.35; 95% CI, 0.130.90). Patients with higher VEGF-D expression received less benefit (VEGF-D 2þ PFS HR, 0.67; 95% CI, 0.451.00; OS HR, 0.82; 95% CI, 0.521.30; VEGF-D 3þ PFS HR, 0.77; 95% CI, 0.501.17; OS HR, 1.28; 95% CI, 0.792.09) (P interaction o0.05). In CAIRO-2, there was no difference in PFS or OS according to VEGF-D expression. CONCLUSIONS: The predictive value of VEGF-D expression for bevacizumab may depend on the chemotherapy backbone used. Further evaluation is required before clinical utilisation.