1. When and which aggressive treatment ? CHEMOTHERAPY IN CTCL
N. Pimpinelli
Dept. Dermatological Sciences
University of Florence Med. School
Florence, Italy

2. CHEMOTHERAPY in CTCL: WHEN
CHEMOTHERAPY in CTCL: WHEN ? advanced MF (stage IIB-IV) SS (high tumor load) CD30+ ALC (disseminated lesions) SPLTL (with progressive lesions) EXTRANODAL NK/T-CELL LY, NASAL TYPE PTL-U (with few exceptions) any refractory CTCL

6. CHEMOTHERAPY IN ADVANCED MF:
monoCT vs. poliCT
2-CDA (Kuzel et al. 1996; Trautinger et al – 51-55% OR)
Pentostatin (Kurzrock et al – 71% OR)
Gemcitabine (Zinzani et al. 1998, 2000; Marchi et al. 2005; Duvic et al – 68-75% OR)
Peg-Doxo (Wollina et al. 2003; Pulini et al. submitted – 86-88% OR)
PFS mos.
PoliCT (Bunn et al. 1884; Fierro et al. 1997; Apisarnthanarax et al. 2002; Cantonetti et al. 2005) – 57-90% OR)
PFS 5-11 mos.

7. poliCT results in stage IIB/IVB better than in III/IVA
CHEMOTHERAPY IN ADVANCED MF:
monoCT vs. poliCT
monoCT > poliCT
(much less side effects and immunosuppression)
poliCT
if high tumor load and generally in stage IV pts.
results in stage IIB/IVB better than in III/IVA

10. Patients with Sézary Syndrome (SS) with a low tumor load, oral chemotherapy (chlorambucil plus prednisone) is a possible treatment alternative to ECP, denileukin diftitox, and IFN.
Patients with high tumor load and patients refractory to/relapsing after a first line treatment should be treated with chemotherapy, (monoCT vs. poliCT ? Consider risk of immunosuppression and quality of life). Consider possible combination treatments, either concurrent or sequential (bexarotene, alemtuzumab)

11. WWhittaker et al, 2003; Dummer et al, 2003; Willemze et al, 2005
Patients with primary cutaneous CD30+ ALC lymhoma with progressing, multiple lesions in non-contiguous sites (and those with regional nodal involvement) can benefit of polychemotherapy (CHOP-like regimens), with a considerable cure rate.
WWhittaker et al, 2003; Dummer et al, 2003; Willemze et al, 2005

12. WWhittaker et al, 2003; Dummer et al, 2003; Willemze et al, 2005
In patients with subcutaneous, panniculitis-like T-cell lymphoma, chemotherapy (monoCT vs. poliCT) is recommended for patients with multiple and/or progressing lesions.
WWhittaker et al, 2003; Dummer et al, 2003; Willemze et al, 2005

13. Whittaker et al, 2003; Dummer et al, 2003; Willemze et al, 2005
PPolychemotherapy (CHOP-like regimens) is recommended as palliative treatment in extranodal NK/T-cell ly. nasal type and primary cutaneous peripheral T-cell lymphoma-U, due to their by far generally aggressive course.
Hvery good ORR (up to 100% in front line) with monoCT (Gemcitabine – Zinzani et al. 2000, Marchi et al. 2005; Peg-Doxo – Pulini et al, submitted)
PPatients with isolated or localized lesions and CD4+ small/medium pleomorphic T-cell histology should be treated non-aggressively at presentation (radiotherapy, surgical excision in unilesional cases).
Whittaker et al, 2003; Dummer et al, 2003; Willemze et al, 2005

14. What patients should be considered for autologous or allogeneic stem cell transplantation ?

15. problems and future directions
Chemotherapy in CTCL:
problems and future directions
improving response: optimization of combination therapy
improving progression-free survival: sequential consolidation with non-cytotoxic agents (oral bexarotene, low-dose alemtuzumab, IFN ?)
improving quality of life: careful balance of pros and cons

16. THANK YOU ! Pimpi & co. S. Rupoli (Ancona) M.G. Bernengo (Torino)
R. Alterini (Firenze)
M. Cantonetti (Roma)
P.L. Zinzani (Bologna)