1. CTCL: INNOVATIVE TREATMENTS GEMCITABINE
Monica Tani
Institute of Hematology and Medical Oncology
“L. e A. Seràgnoli”
University of Bologna, Italy

2. GEMCITABINE
Gemcitabine is a novel nucleoside analog that exerts its antitumor activity via multiple mechanisms of action. These include:
Incorporation of gemcitabine into replicating DNA, which inhibits DNA replication and cell growth.
Institute Seràgnoli

3. Masked DNA chain termination.
GEMCITABINE
Masked DNA chain termination.
Several self-potentiation mechanisms that serve to increase intracellular levels of the active compound.
Like the ara-C analogue, gemcitabine may be an active drug in lymphoproliferative disorders.
Institute Seràgnoli

4. All cycles can be delivered on an outpatient basis
GEMCITABINE
Schedule:
Gemcitabine mg/m² (over 30 minutes) on day 1, 8 and 15 of a 28-day schedule for a total of 3-6 cycles
All cycles can be delivered on an outpatient basis
Institute Seràgnoli

5. All pretreated with polychemotherapy (CHOP and others)
GEMCITABINE
13 pretreated patients with PTCL with isolated skin involvement (5 MF, stage IIb-III; 8 unspecified, stage IV)
All pretreated with polychemotherapy (CHOP and others)
Gemcitabine 1200mg/m², day 1, 8, 15 cycles for 3 courses
1 CR, 8 PR, 4 NR
ZINZANI et al (Ann Oncol 1998)
Institute Seràgnoli

6. ZINZANI et al (JCO 2000) GEMCITABINE * TNM classification
** Ann Arbor Staging System
ZINZANI et al (JCO 2000)
Institute Seràgnoli

7. MF (n=30) PTCLU (n=14) Total (n=44) CR (%) 3* (10) 2** (14) 5 (11,5)
GEMCITABINE MF
(n=30)
PTCLU
(n=14)
Total
(n=44)
CR (%)
3* (10)
2** (14)
5 (11,5)
PR (%)
18 (60)
8 (57)
26 (59)
CR+PR (%)
21 (70)
10 (71)
31 (70,5)
* 1 with histologic CR
** 1 with histologic CR
ZINZANI et al (JCO 2000)
Institute Seràgnoli

8. RESPONSE ACCORDING TO PREVIOUS TREATMENTS AND TO DISEASE STATUS
GEMCITABINE
RESPONSE ACCORDING TO PREVIOUS TREATMENTS AND TO DISEASE STATUS
No. of
pts
CR (%)
PR (%)
CR+PR
(%)
Relapsed 34
4 (12)
20 (59)
24 (71)
Refractory 10
1 (10)
6 (60)
7 (70)
Prior regimens: 2 3
 4 19 15
3 (16)
2 (13)
12 (63)
9 (60)
5 (50)
15 (79)
11 (73)
ZINZANI et al (JCO 2000)
Institute Seràgnoli

9. Hematological toxicities:
GEMCITABINE
Hematological toxicities:
anemia of WHO grade III was observed in 5-10% of patients; neutropenia of WHO grades III and IV in 20% and 10% of patients, respectively; WHO grade III and IV thrombocytopenia in 20% and 10% of patients, respectively
Non-hematological toxicity:
transient elevations in liver transaminases were observed in 5-10% of patients; renal and pulmonary toxicity was very rare, WHO grade III-IV less than 1%; flu-like symptoms with headache, fever, myalgias and fatigue occurred in up to 10% of patients; usually, no alopecia occurs during Gemcitabine therapy
Institute Seràgnoli

10. SALLAH et al (Br J Haematol 2001)
GEMCITABINE
SALLAH et al (Br J Haematol 2001)
10 patients with relapsed or refractory T-cell malignancies (2 CTCL, 2 PLL, 2 nodal PTCL, 2 SLL, 1 ALC, 1 angiocentric LNH)
Gemcitabine at a dose of 1200mg/m² on day 1, 8, and 15 of each 28-day cycle
2 CR (1 PLL, 1 anaplastic) 4 PR (2 CTCL, 1 PTCL, 1 angiocentric)
Median DR: months for CR months for PR
ORR
60%
Institute Seràgnoli

11. DUVIC et al (Clinical Lymphoma & Myeloma 2006)
GEMCITABINE
DUVIC et al (Clinical Lymphoma & Myeloma 2006)
33 patients with relapsed or refractory advanced heavily pretreated CTCL
Gemcitabine at a dose of 1000mg/m² on day 1, 8, and 15 of each 28-day cycle for six or more cycles
2 ALC CD30+
31 MF (11 SS)
3 CR
14 PR
Median DR: < 1 year
ORR
68%
Institute Seràgnoli

12. ITALIAN CUTANEOUS LYMPHOMA STUDY GROUP
GEMCITABINE
ITALIAN CUTANEOUS LYMPHOMA STUDY GROUP
Phase II study of Gemcitabine as primary chemotherapy of patients with advanced CTCL (eventually pretreated only with PUVA or RT)
Population studied: MF and PTCLU with exclusive skin involvement
Conventional dose: 1200mg/m² on days 1, 8, and 15 of a 28-day schedule for 6 cycles
Cancer 2005
Institute Seràgnoli

13. PATIENTS’ CHARACTERISTICS OF THE STUDY GROUP
GEMCITABINE
PATIENTS’ CHARACTERISTICS OF THE STUDY GROUP
Institute Seràgnoli

14. GEMCITABINE
TREATMENT OUTCOME
Institute Seràgnoli

15. GEMCITABINE
TREATMENT TOXICITY
Institute Seràgnoli

16. PROGRESSION FREE SURVIVAL CURVE OF ALL RESPONDER PATIENTS
GEMCITABINE
PROGRESSION FREE SURVIVAL CURVE OF ALL RESPONDER PATIENTS
months 24 21 18 15 12 9 6 3
1,0 ,9 ,8 ,7 ,6 ,5 ,4 ,3 ,2 ,1
0,0
Institute Seràgnoli

17. OVERALL SURVIVAL CURVE OF ALL STUDY POPULATION
GEMCITABINE
OVERALL SURVIVAL CURVE OF ALL STUDY POPULATION
months 42 36 30 24 18 12 6
1,0 ,9 ,8 ,7 ,6 ,5 ,4 ,3 ,2 ,1
0,0
Institute Seràgnoli

18. CONCLUSIONS Impressive single agent data Brief treatment
GEMCITABINE
CONCLUSIONS
Impressive single agent data
Brief treatment
Outpatient administration
Excellent activity to toxicity ratio
Future:
Larger trials to consolidate these data
First-line treatments
In combination with other drugs:
Fludarabine
Oxaliplatin
Campath-1H
Institute Seràgnoli

19. PHASE II STUDY IN PRETREATED CTCL
GEMCITABINE
PHASE II STUDY IN PRETREATED CTCL
GEMCAM: Gemcitabine 1200 mg/m2 day Campath-1H 10 mg (total dose) day every 28 days for a total of 6 cycles
Institute Seràgnoli