Non-Hodgkin’s Lymphoma, extranodal primaries                                                                                      87

 

13.          Non-Hodgkin’s Lymphoma, extranodal primaries

 

 

13.4        Primary central nervous system NHL (PCNSL)

 

13.4.1 General considerations

The management of PCNSL is quite different from the usual treatment of systemic NHL. Standard chemotherapy regimens used in systemic NHL are ineffective, mainly due to the existence of the blood-brain-barrier. Whole brain radiation was therefore the cornerstone of the therapy for decades. It resulted in high response rates, however, of short duration and was burdened with delayed neurotoxicity. The combination of radio-and chemotherapy based on high-dose methotrexate proved very efficient in terms of survival rate, but again was overshadowed by a high incidence of delayed cognitive neurotoxicity (particularly in patients older than 60 years). Chemotherapy alone with protocols based on high-dose methotrexate (alone or in combination) thus far resulted in promising survival rates and quality of life in unicentric studies. Which need to be substantiated in larger multicentric trials. The role of myeloablative chemotherapy with  stem cell rescue is also under investigation.

 

Literature: for review e.g.

            AMBINDER and SPARANO, Cancer Treat. Res. 104 (2001): 231-246

            BASSO and BRANDES, Eur. J. Cancer 38 (2002): 1298 – 1312

            De ANGELIS, Curr, Treatm. Options Oncol. 2 (2001): 309-318

            FERRERI et al, J. Clin. Oncol. 21 (2003) 266-272 (prognostic scoring

            system)

            McALLISTER, Curr. Neurol. Neurosci, Rep. 2 (2002): 210 – 215

            PARK and ABREY, Expert Opin. Pharmacother. 3 (2002): 39 – 49

            PLASSWILM et al, Ann. Hematol. 81 (2002): 415- 423

RENI and FERRERI, Ann. Hematol. 80 (Suppl 3) (2001): 113- 117 (management of refractory/ relapsed PCNSL)

90                                                                                         Non-Hodgkin’s Lymphoma, extranodal primaries 

 

            RTOG study 93 – 10

Methotrexate                    2500 mg/m2              i.v. (2-3 h inf)              d 1, every other wk x 5

                                                                                                                (wk 1, 3, 5, 7, 9 )

Folinic acid                       20 mg                       p.o.                                every 6 h for 12 doses

                                                                                                                  (wk 1, 3, 5, 7, 9)

Vincristine                         1.4 mg /m2                i.v.                               d 1, every other wk x 5

                                          (max 2.8 mg)                                                  (wk 1, 3, 5, 7, 9 )

Procarbazine                      100 mg/m2                p.o.                               d 1 (wk 1, 5, 9 )

Dexamethasone                  16 ← 2 mg*             p.o.                               d 1-7 (wk 1-6)

Methotrexate                       12 mg                      i.th.**                           d 1 (wk 2, 4, 6, 8, 10)

Folinic acid                          10 mg                      b.i.d. p.o                       for 8 doses (wk 2, 4,  6,

                                                                                                                    8, 10 )

*  16 mg/d for the first week, decreasing to 12, 8, 6, 4 and 2 mg/d over the next 5 wks

** Ommaya reservoir

 

Followed by whole brain radiotherapy (45 Gy in 1.8 Gy fractions, wk 11 – 15 )

 

Cytarabine                          3000 mg/m2               i.v. (3 h inf)                  2 doses separated by

                                                                                                                   24 h (wk 16 + 19)

 

Literature :

            De ANGELIS  et al , J . Clin . Oncol  . 20(2002) : 4643 – 4648 .

GUITART et al, Arch. Dermatol. 138 (2002): 1359-1365 (allogeneic hematopoietic stem cell transplantation)

                        STADLER, Skin Pharmacol. Appl. Skin Physiol. 15(2002): 139 – 146

                        VONDERHEID, Recent Results Cancer Res. 160 (2002): 309 – 320

 

13.2.2.2                  Bexarotene

Bexarotene                    300 – 400 mg/m2                        p.o.                   daily

 

The capsules are taken as a once-daily dose with meals. The time to response is generally within 2 months. A topically applicable gel formulation is also available.

           

            Literature:

BRENEMAN et al, Arch, Dermatol. 138 (2002): 325-332 (phase I and II trial of  bexarotene gel)

DUVIC et al, J. Clin. Oncol. 19 (2001): 2456-2471 (multinational phase II and III trial results)

TALPUR et al, J. Am. Acad. Dermatol. 47 (2002): 672-684 (oral bexarotene as monotherapy and in combination with other active agents)

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13.2.2.3                  Denileukin diftitox (DAB- IL2)

Denileukin           9 or 18 µg/kg                     i.v.(15- 60 min inf)             d 1 - 5     

            Every 3 weeks (max 8 cycles or 6 months of therapy) with corticosteroid premedication.

 

For the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma whose malignant cells express the CD25 component of the IL-2 receptor.

           

            Literature:

                        DUVIC et al, Clin. Lymphoma 2 (2002): 222-228 (quality of life aspects)

                        OLSEN et al, J. Clin. Oncol. 19 (2001): 376- 388 (phase III pivotal trial)