42                                                                                                                           Hodgkin’s Lymphoma(HL) ______________________________________________________________________________________

8.             Hodgkin’s Lymphoma (HL)

8.2.1    First- line chemotherapy

8.2.1.1 ABVD

                To be repeated every 4 weeks

                  Literature:

                        BONADONNA et al, Ann. Intern. Med. 104 (1986): 739- 746

                        BONADONNA and SANTORO, Cancer Treat. Rev. 9 (1982): 21-35

                        CHISESI et al, Ann. Oncol.13 (Suppl 1) (2002): 102-106 (randomized  

                        trial of ABVD vs  Stanford V vs MEC in unfavorable HL)

8.2.1.2     MOPP/ABV hybrid regimen

To be repeated every 4 weeks

Literature:

     FERME et al, Blood 95 (2000): 2246 – 2252

     GLICK et al, J. Clin. Oncol. 16 (1998): 19 – 26 .

     KLIMO and CONNORS, J. Clin. Oncol. 3 (1985): 1174 – 1182

8.2.1.3     ChlVPP/ EVA hyhrid regimen

               *  Max. 2 mg for patients ≥ 60 years, and 0.7 mg/m² for patients ≥ 70 years

             **  Dose escalated from 75 mg/m² in first cycle to 100 mg/m² in subsequent  

                   cycles if oral mucositis is not > CTC grade 1 after first exposure

                  To berepeated every 4 weeks(6 cycles, then radiotherapy to sites of previous  

                  bulk or residual radiographic abnormality).

                  Literature:

                        RADFORD et al, J. Clin. Oncol. 20 (2002): 2988 – 2994 (randomized

                        comparison) of ChIVPP/ EVA hybrid vs a weekly VAPEC – B regimen)

Hodgkin’s Lymphoma (HL)                                                                                                                        45 _____________________________________________________________________________________

8.2.1.4     COPP- ABVD alternating regimen

To be repeated every 8 weeks

Literature:

            SIEBER et al, J. Clin. Oncol. 20 (2002): 476 – 484

8.2.1.5     BEACOPP and BEACOPP “ escalate”

To be repeated every 3 weeks (8 cycles for advanced stage disease: 4 escalated and 4 base- line)

*Dose-escalated regimen with G-CSF support

Patients > 65 have not benefited from the BEACOPP regimen. For all others, tumor control and overall survival were markedly improved using BEACOPP compared to standard therapy (COPP/ABVD). G-CSF-supported dose escalation brings further benefit in tumor for control patients up to 60 years old.

Literature:

DIEHL et al, J. Clin. Oncol. 16 (1998): 3810-3821 and Ann. Oncol. 9  

(Suppl 5)(1998): 67-71

ENGEL et al, Ann. Oncol. 11(2000) : 1105-1114       

FRANKLIN and DIEHL, Ann. Oncol. 13 (Suppl 1) (2002): 98 – 101

8.2.1.6     Stanford V

With consolidative readitherapy

   *  Reduced to 4 mg/m² resp. 1 mg/m² during weeks 10 – 12 for patients ≥ 50 years  

      of age.

      ** Tapered by 10 mg every other day starting at week 10.

46                                                                                                                           Hodgkin’s Lymphoma(HL) _______________________________________________________________________

            Literature:

                        CHISESI et al, Ann. Oncol. 13 (Suppl 1) (2002): 102-106 (randomized

                        trial of  ABVD vs Stanford V vs MEC  in unfavorable HL)

                        HORNING et al, J. Clin. Oncol. 20 (2002): 630-637

8.2.2            Salvage and reinduction chemotherapy

8.2.2.1    MIME

            To be repeated every 3 weeks. In combination with G-CSF also efficient stem cell mobilization.*

            Literature:

                     * AURLIEN et al, Eur. J. Haematol. 66 (Suppl 64) (2001): 14 – 20

                        HAGEMEISTER et al, J. Clin. Oncol. 5 (1987) : 556 – 561

8.2.2.2     ICE

To be repeated every 2 weeks (2 cycles). With G- CSF support. For cytoreduction and stem cell

mobilization.

Literature:

            MOSKOWITZ et al, Blood 97 (2001): 616-625 and Cancer Chemother.

            Pharmacol. 49 (Supp 1) (2002): 9 – 12

8.2.2.3     IVE

        To be repeated every 3 weeks ( target total of 3 courses). With G-CSF support.

        For cytoreduction and  stem cell mobilization.

        Literature :

                    JACKSON et al, Leuk. Lymph. 37 (2000):  561 – 570

                    McQUAKER et al, Bone Marrow Transplant. 24 (1999): 715 – 722

                    PROCTOR et al, Eur. J. Haematol. 66 (Suppl 64) (2001): 28 – 32

8.2.2.4     Ifosfamide + Vinorelbine

        To be repeated every 3 weeks. With G-CSF support.

            Litrature:

                        BONFANTE et al, Br. J. Haematol. 103 (1998): 533 – 535 and Eur. J.

                        Haematol. 66 (Suppl 64) (2001): 51 – 55

8.2.2.5 DEXA- BEAM

            To be repeated every 4 weeks. With G- CSF support (2-4 courses followed by  

            high-dose therapy and hematopoietic stem cell rescue).

            Literature:

                        JOSTING et al, Ann. Oncol. 9 (1998): 289 – 295

                        SCHMITZ et al, Lancet 359 (2002): 2065 – 2071 (randomized comparsion

                        of aggressive conventional chemotherapy and of high- dose chemotherapy

                        with autologous stem cell transplantation)

8.2.2.6 ASHAP

              For 3 cycles ( in patients having at least stable disease after 2 cycles ) followed by

              high-dose therapy.

              Literature:

                        RODRIGUEZ et al, Blood 93 (1999): 3632 – 3636

8.2.3        hematopoietic stem cell transplantation

High-dose chemotherapy (e.g. CBV or BEAM) followed by autologous stem cell transplantation has resulted in long- term event-free survival in at least one third of selected patients with relapsed or refractory HL. No randomized trials have been performed versus allogeneic stem cell transplantation, but historical comparison showed a significantly lower relapse rate for allografting. This advantage, however, is offset by a high transplant-related morbidity and mortality. The use of nonmyeloablative regimens preceding allografting has been started to combine the postitive effects of a graft- versus- Hodgkin’s lymphoma effect with a better tolerability than that observed after conventional allografting.

Literature: for review and representative studies e.g.

            ANDRE et al, J. Clin. Oncol. 17(1999): 222-229 (comparison of

            conventional and high-dose therapy with autologous stem cell

            transplantation)

            ANSELMO et al, Ann. Haematol. 79 (2000): 79 – 82

            ARGIRIS et al, Ann. Oncol. 11 (2000):665 – 672

            CARELLA, Clin, Lymphoma 2 (20002): 212 – 221

            LAZARUS et al, Bone Marrow Transplant. 27 (2001): 387 – 396 (report

            from the ABMTR on autotransplantation for patients in first relapse or

            second remission)

            REECE, Cancer Contr.7 (2000): 266-275 and Curr. Opin. Oncol.

            14(2002): 165-170

            SCHMITZ et al, Lancet 359 (2002): 2065 – 2071 (randomized comparison

            of aggressive concentional chemotherapy and high-dose chemotherapy

            with autologous stem cell transplantation)

SUREDA and SCHMITZ, Ann. Oncol. 13 (Suppl 1) (2002): 128 – 132 (role of allogeneic stem cell transplantation)

SUREDA et al, J. Clin. Oncol. 19 (2001): 1395 – 1404

8.2.4                HIV- associated Hodgkin’s lymphoma

                  At present, no optimal therapy for HIV-associated Hodgkin’s lymphoma has been

defined. With standard chemotherapy regimens CR rates remain below those

reported in patients without HIV infections and tolerance is poor. Improved results

have been reported more recently by the use of intensive chemo(radio)therapy with

concomitant HAART (highly active antiretroviral therapy) and G-CSF support.

Literature:

                        GERARD et al, AIDS 17 (2003): 81-87 (retrospective single institution study

which showed that overall survival has significantly improved since

introduction of HAART)

SPINA et al, Blood 100 (2002): 1984 – 1988 (phase 2 study of Stanford V +

HAART + G-CSF)

VACCHER et al, Eur, J. Cancer 37 (2001): 1306 – 1315 (review)

8.2.4        Hodgkin’s lymphoma in the elderly

It is generally agreed that- compared to treatment in younger patients – higher rates of toxicity and more frequent early relapsed have to be expected in elderly patients.

Different combinations of effective therapies with low toxicity are therefore felt to be required. Liberal support with hematopoietic growth factors (G-CSF) is also considered necessary to reduce prolonged neutropenia.

Literature:

            PROCTOR et al, Ann. Oncol. 13 (Suppl 1) (2002): 133-137 (review)

            WEEKS et al. J. Clin. Oncol. 20 (2002): 1087-1093 (comparison of

            ChlVPP/ABV hybrid with ChlVPP alone)

VEPEMB

To be repeated every 4 weeks

Literature:

            PROCTOR et al, Ann. Oncol. 13 (Suppl 1) (2002): 133 – 137 (review)