redazione@vetpedia.it +39-0372-40-35-36/37/47

Chemotherapy protocols for the treatment of lymphoma in the dog

Details
Category: Schede
Hits: 10
  • Disciplina: Oncologia
  • Specie: Cane

Polychemotherapy regimens for the treatment of high-grade lymphoma in the dog.

 

FIRST-LINE TREATMENT OF HIGH-GRADE LYMPHOMA

COP: induction and maintenance

Drug

Low-dose protocol

High-dose protocol

Cyclophosphamide

50 mg/m2per os on alternate days for 8 weeks, or 50 mg/m2 per os for 4 consecutive days (days 4-7) for 8 weeks, then the same dose but in alternate weeks for 4 months, then every 21 days for 6 months and finally once a month for 1 year.

250-300 mg/m2per os or i.v. every 21 days for 1 year, then once a month for another 6 months, then interrupt if the dog is in complete remission.

Vincristine

0.5 mg/m2 i.v. once a week (day 1) for 8 weeks, then in alternate weeks for 4 months, then every 21 days for 6 months and finally once a month for 1 year.

0.75 mg/m2 i.v. once a week for 8 weeks, then in alternate weeks for 4 months, then every 21 days for 6 months and finally once a month for 1 year.

Prednisone

20 mg/m2per os s.i.d. or 1 mg/kg/die for 7 days, then on alternate days until relapse or appearance of side effects.

20 mg/m2per os s.i.d. or 1 mg/kg/die for 7 days, then on alternate days until relapse or appearance of side effects.

 

CHOP: induction and maintenance

Drug

Induction regimen

Maintenance regimen

Cyclophosphamide

50 mg/m2 per os on alternate days for 8 weeks.

 

Vincristine

0.5-0.7 mg/m2 i.v. on days 8 and 15.

 

Prednisone

20 mg/m2 per os s.i.d. for 7 days, then on alternate days.

 

Doxorubicin

30 mg/m2 i.v. on day 1.

30 mg/m2 i.v. from day 22 every 21 days.

 

ACOPA-I: induction and maintenance

Drug

Administration protocol

L-asparaginase

10000 IU/m2 i.m. weeks 1, 2, 3 and 4.

Vincristine

0.75 mg/m2 i.v. weeks 1, 2, 3, 4, 7, 10, 13, 16, 25, 28, 31, 40, 43, 46, 55, 58, 61, 70 and 75.

Cyclophosphamide

250 mg/m2per os weeks 7, 13, 16, 28, 31, 43, 46, 58, 61 and 75.

Prednisone

40 mg/m2 per os s.i.d. for 7 days, then on alternate days.

Doxorubicin

30 mg/m2 i.v. weeks 10, 25, 40, 55 and 70.

 

Madison-Wisconsin protocol: induction and maintenance

Drug

Induction regimen (10 weeks)

Maintenance regimen

L-asparaginase

400 IU/kg s.c. week 1.

 

Vincristine

0.7 mg/m2 i.v. weeks 1, 3, 6 and 8.

0.7 mg/m2 i.v. weeks 11, 15, 19, 23, 28 and 34.

Cyclophosphamide

200 mg/m2 i.v. weeks 2 and 7.

 

Chlorambucil

 

1.4 mg/kg per os weeks 13, 21 and 31.

Prednisone

2 mg/kg per os s.i.d. for 7 days, then 1.5 mg/kg per os for 7 days, followed by 1 mg/kg for 7 days and then 0.5 mg/kg per os for 7 days.

 

Doxorubicin

30 mg/m2 i.v. weeks 4 and 9.

30 mg/m2 i.v. weeks 17 and 25.

Methotrexate

 

0.5-0.8 mg/kg i.v. week 37.

 

VCAA

Drug

Administration protocol

L-asparaginase

400 IU/kg s.c. weeks 1 and 6.

Vincristine

0.75 mg/m2 i.v. weeks 2 and 7.

Cyclophosphamide

75 mg/m2per os for 4 consecutive days, weeks 3 and 8.

Doxorubicin

30 mg/m2 i.v. weeks 4 and 9.

 

ACOPA-II: induction and maintenance

Drug

Administration protocol

L-asparaginase

10000 IU/m2 i.m. weeks 7, 8, 25 and 26.

Vincristine

0.75 mg/m2 i.v. weeks 4, 10, 13, 16, 19, 22, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71 and 74.

Cyclophosphamide

250 mg/m2per os weeks 4, 7, 13, 16, 22, 32, 35, 39, 42, 48, 51, 57, 58, 65, 66, 74 and 75.

Prednisone

40 mg/m2per os s.i.d. for 7 days, then on alternate days.

Doxorubicin

30 mg/m2 i.v. weeks 1, 10, 19, 29, 38, 47, (56), (64), (73).

 

Doxorubicin, L-asparaginase and COP: induction and maintenance

Drug

Induction regimen

Maintenance regimen

Doxorubicin

30 mg/m2 i.v. every  weeks.

 

L-asparaginase

10000 IU/m2 i.m. for 3 weeks.

 

Cyclophosphamide

 

200-250 mg/m2per os every 21 days.

Vincristine

 

0.75 mg/m2 once a week for 4 weeks, then every 3 weeks.

Prednisone

 

1 mg/kg/die per os for 4 weeks, then on alternate days.

 

VELCAP: induction and maintenance (VELCAP-L)

Drug

Induction regimen (12 weeks)

Maintenance regimen

Cyclophosphamide

250 mg/m2per os weeks 7 and 12.

250 mg/m2per os: weeks 15, 21, 24, 28, 31, 43, 46, 58, 61 and 73.

Vincristine

0.75 mg/m2 i.v. once a week for 3 weeks, then only weeks 7 and 12.

0.75 mg/m2: weeks 15, 18, 21, 27, 28, 31, 34, 43, 46, 49, 58, 61, 64 and 73.

L-asparaginase

10000 IU/m2 s.c. weeks 7, 8 and 9.

10000 IU/m2 s.c. weeks 24 and 25.

Doxorubicin

30 mg/m2 i.v. weeks 2 and 4.

30 mg/m2 i.v. week 18, 27, 34, 49 and (64).

Prednisone

40 mg/m2per os s.i.d. for 7 days, then on alternate days.

40 mg/m2per os on alternate days.

 

COPLA/LVP: induction and maintenance

Drug

Induction regimen (12 weeks)

Maintenance regimen

L-asparaginase

10000 IU/m2 s.c. (days 1 and 8).

 

Vincristine

0.5 mg/m2 i.v. once a week (from day 1) for 11 weeks, omitting weeks 6 and 9.

0.5 mg/m2 i.v. from week 12 every 2 weeks for two treatments, then every 3 weeks for three treatments, then every month.

Cyclophosphamide

50 mg/m2per os on alternate days for 8 weeks.

 

Prednisone

20 mg/m2 per os s.i.d. for 7 days, then on alternate days for 7 weeks.

 

Doxorubicin

30 mg/m2 i.v. every 21 days (weeks 6, 9 and 12).

 

Chlorambucil

 

4 mg/m2 per os on alternate days.

 

Modified VELCAP: only induction (VELCAP-S)

Drug

Induction regimen (12 weeks)

Cyclophosphamide

250 mg/m2 per os: weeks 7 and 12.

Vincristine

0.75 mg/m2 i.v. once a week for 3 weeks, then only weeks 7 and 12.

L-asparaginase

10000 IU/m2 s.c. weeks 7, 8 and 9.

Doxorubicin

30 mg/m2 i.v. weeks 2 and 4.

Prednisone

40 mg/m2 per os s.i.d. for 7 days, then on alternate days.

 

Modified Madison-Wisconsin protocol

Drug

Administration protocol (25 weeks)

L-asparaginase

400 IU/kg s.c. week 1.

Vincristine

0.5-0.7 mg/m2 i.v. weeks 1, 3, 6, 8, 11, 15, 19 and 23.

Cyclophosphamide

250 mg/m2 i.v. weeks 2, 7, 13 and 21.

Prednisone

2 mg/kg per os s.i.d. for 7 days, then 1.5 mg/kg per os for 7 days, then 1 mg/kg for 7 days, then 0.5 mg/kg per os for 7 days.

Doxorubicin

37.5 mg/m2 i.v. weeks 4, 9, 17 and 25.

 

VELCAP-S with consolidation(MOPP and lomustine)

Drug

Induction regimen (11 weeks)

Maintenance/consolidation regimen

 

Cyclophosphamide

250 mg/m2per os weeks 5 and 9.

 

 

Vincristine

0.75 mg/m2i.v. weeks 1, 2, 5 and 9.

0.75 mg/m2 weeks 13 and 14.

 

L-asparaginase

10000 IU/m2 s.c. weeks 1 and 4.

 

 

Doxorubicin

30 mg/m2 i.v. weeks 3, 7 and 11.

 

 

Prednisone

40 mg/m2 per os s.i.d. for 7 days, then on alternate days for 4 weeks.

40 mg/m2/die per os week 13.

40 mg/m2 on alternate days per os week 14.

 

Mechlorethamine

 

3 mg/m2 i.v. weeks 13 and 14.

 

Procarbazine

 

50 mg/m2per os s.i.d. from week 13 for 14 days.

 

Lomustine

 

90 mg/m2per os weeks 17 and 20.

 

Short German protocol: induction

Drug

Induction regimen (12 weeks)

L-asparaginase

400 IU/kg s.c. week 1.

Vincristine

0.7 mg/m2 i.v. weeks 1, 4, 7 and 10.

Cyclophosphamide

200 mg/m2 i.v. weeks 2, 5, 8 and 11.

Doxorubicin

30 mg/m2 i.v. weeks 3, 6, 9 and 12.

Prednisolone

50 mg/ m2 per os days 1-3 of weeks 1 to 12.

 

L-asparaginase and MOPP

Drug

Administration protocol

L-asparaginase

400 IU/kg i.m. week 1

Mechlorethamine

3 mg/m2 i.v. week 2 (day 1) and week 3 (day 1).

Vincristine

0.7 mg/m2 i.v.: week 2 (day 1) and week 3 (day 1).

Procarbazine

50 mg/m2per os s.i.d. start in week 2: days 1-14.

Prednisone

30 mg/m2per os s.i.d.: start in week 2: days 1-14.

 

CHOP-MA

Drug

Induction

Maintenance

Consolidation

L-asparaginase

400 IU/kg i.p. week 1 (day 1)

 

400 IU/kg i.p. week 57

Vincristine

0.7 mg/m2 i.v. weeks 1 (day 1), 4, 8 and 14

0.7 mg/m2 i.v. weeks 21, 27, 33, 39, 45 and 51

0.7 mg/m2 i.v. weeks 57 and 59

Cyclophosphamide

200 mg/m2i.v. weeks 2 (day 1), 5, 10 and 16

200 mg/m2 i.v. weeks 24, 36 and 48

200 mg/m2 i.v. weeks 58 and 60

Doxorubicin

30 mg/m2 i.v. weeks 3 (day 1), 6, 12 and 18

 

 

Prednisone

30 mg/m2per os for 7 days, then 20 mg/m2 for 7 days, then 10 mg/m2 for 7 days

 

 

Mitoxantrone

 

6 mg/m2 i.v. weeks 30, 42 and 54

 

 

L-CHOP-CCNU-MOPP

Drug

Induction

Maintenance

L-asparaginase

400 IU/kg s.c. weeks 1 and 7.

 

Vincristine

0.5 mg/m2 i.v. weeks 1, 4, 8, 11 and 12.

Weeks 18, 24 and 25.

Cyclophosphamide

200 mg/m2 i.v. week 2.

Week 20.

Doxorubicin

30 mg/m2 i.v. weeks 3 and 9.

Weeks 14 and 22.

Lomustine

90 mg/m2per os week 6.

Week 16

Mechlorethamine

3 mg/m2 i.v. weeks 11 and 12.

Weeks 24 and 25.

Procarbazine

50 mg/m2per os for 14 days: week 11.

Week 24.

Prednisone

30 mg/m2s.i.d. for 7 days, then 20 mg/m2s.i.d. for 7 days, then 10 mg/m2 for 14 days, then interrupt.

Restart at 40 mg/m2s.i.d. for 14 days from week 11, then interrupt. Restart at 40 mg/m2s.i.d. for 14 days from week 24, then interrupt.

 

Dose-intensified, maintenance-free, CHOP-based

Drug

Administration regimen

L-asparaginase

400 IU/kg s.c. weeks 1 and 6.

Vincristine

0.5 mg/m2 i.v. weeks 2, 3, 7, 8, 12 and 13.

Cyclophosphamide

50 mg/m2per os for 4 consecutive days: weeks 2, 3, 7, 8, 12 and 13.

Doxorubicin

30 mg/m2 i.v. weeks 4, 9, 14, 16, 18 and 20.

Methotrexate

0.6 mg/kg i.v. week 11.

Prednisone

2 mg/kg s.i.d. for 7 days, then 1 mg/kg s.i.d. for 7 days, then 0.5 mg/kg for 14 days, then interrupt.

 

TREATMENT OF MULTICENTRIC LYMPHOMA WITH BONE MARROW INVOLVEMENT

AraC-VCAA

Drug

Administration regimen

Cytosine arabinoside

150 mg/m2 i.v. in a continuous infusion (24 hours) for 5 consecutive days. Repeat in week 6 if bone marrow infiltration (>20%) still present.

L-asparaginase

400 IU/kg s.c. weeks 1 and 6.

Vincristine

0.75 mg/m2 i.v. weeks 2 and 7.

Cyclophosphamide

75 mg/m2per os for 4 consecutive days, weeks 3 and 8.

Doxorubicin

30 mg/m2 i.v. weeks 4 and 9.

 

SECOND-LINE TREATMENT (SALVAGE THERAPY) OF HIGH-GRADE LYMPHOMAS

CCNU

Drug

Administration regimen

Lomustine

90 mg/m2per os every 21 days.

 

MOPP

Drug

Administration regimen

Mechlorethamine

3-6 mg/m2 i.v. days 1 and 8.

Vincristine

0.75 mg/m2 i.v. days 1 and 8.

Procarbazine

50 mg/m2per os s.i.d. days 1-14.

Prednisone

30-40 mg/m2per os s.i.d.

 

DMAC

Drug

Administration regimen

Dexamethasone

1 mg/kg per os/s.c. days 1 and 8.

Cytosine arabinoside

300 mg/m2 s.c./i.v. (in 4 hours) day 1.

D-actinomycin

0.75 mg/m2 i.v. day 1.

Melphalan

20 mg/m2per os s.i.d. day 8.

 

L-asparaginase, lomustine and prednisone

Drug

Administration regimen

Lomustine

Dogs ≥ 15 kg: 70 mg/m2per os every 21 days;

Dogs < 15 kg: 60 mg/m2per os every 21 days.

L-asparaginase

400 IU/kg s.c. together with the first two doses of  lomustine

Prednisone

2 mg/kg per os s.i.d. to taper down to 1 mg/kg every other day.

 

DTIC

Drug

Administration regimen

Dacarbazine

800-1000  mg/m2 i.v. in 100-250 ml NaCl in 4-5 hours. Repeat every 21 days.

 

CCNU-DTIC

Drug

Administration regimen

Lomustine

40 mg/m2per os day 1

Dacarbazine

600 mg/m2 i.v. in 250 ml -1 l NaCl in 5 hours.

 

Suggested readings

  1. Alvarez FJ, Kisseberth WC, Gallant SL, Couto CG: Dexamethasone, melphalan, actinomycin D, cytosine arabinoside (DMAC) protocol for dogs with relapsed lymphoma.J Vet Inter Med. 20: 1178, 2006.
  2. Boyce KL, Kitchell BE: Treatment of canine lymphoma with COPLA/LVP.J Am Anim Hosp Assoc, 36: 395-403, 2000.
  3. Brodsky EM, Maudlin GN, Lachowicz JL, Post GS. Asparaginase and MOPP treatment of dogs with lymphoma.J Vet Intern Med. 23: 578, 2009.
  4. Carter RF, Harris CK, Withrow SJ et al: Chemotherapy of canine lymphoma with histopathological correlation: doxorubicin alone compared to COP as first treatment regimen. J Am Anim Hosp Assoc, 23: 587, 1987.
  5. CotterSM: Treatment of lymphoma and leukaemia with cyclophosphamide, vincristine, and prednisolone: I. treatment of dogs. J Am Anim Hosp Assoc, 19: 159, 1983.
  6. Cotter SM: Treatment of lymphoma and leukaemia with cyclophosphamide, vincristine and prednisone: II. Treatment f cats. J Am Anim Hosp Assoc, 19: 166, 1983.
  7. Cotter SM, GoldsteinM: Comparison of two protocols for maintenance of remission in dogs with lymphoma. J Am Anim Hosp Assoc, 23: 495, 1987.
  8. Daters AT, Mauldin GE, Mauldin GN et al: Evaluation of a multidrug chemotherapy protocol with mitoxantrone based maintenance (CHOP-MA) for the treatment of canine lymphoma. Vet Comp Oncol. 8: 11, 2010
  9. Dervisis NG, Dominguez PA, Sarbu L et al: Efficacy of temozolomide or dacarbazine in combination with an anthracycline for rescue chemotherapy in dogs with lymphoma.J Am Vet Med Assoc. 231: 563, 2007.
  10. FloryAB, Rassnick KM, Al-Sarraf R et al: Combination of CCNU and DTIC chemotherapy for treatment of resistant lymphoma in dogs. J Vet Intern Med. 22: 164, 2008.
  11. Griessmayr PC, Payne SE, Winter JE et al: Dacarbazine as single-agent therapy for relapsed lymphoma in dogs.J Vet Inter Med. 23: 1227, 2009.
  12. Hosoya K, Kisseberth WC, Lord LK, et al. Comparison of COAP and UW-19 protocols for dogs withmulticentric lymphoma.J Vet Intern Med. 21: 1355, 2007.
  13. Lori JC, Stein TJ, Thamm DH: Doxorubicin and cyclophosphamide for the treatment of canine lymphoma: a randomized, placebo-controlled study. Vet Comp Oncol, 8: 188, 2010.
  14. Marconato L, Bonfanti U, Stefanello D et al. Cytosine arabinoside in addition to VCAA-based protocols for the treatment of canine lymphoma with bone marrow involvement: does it make the difference?Vet Comp Oncol, 6: 80, 2008.
  15. MooreAS, Ogilvie GK, VailDM: Actinomycin D for reinduction of remission in dogs with resistant lymphoma.J Vet Intern Med, 8: 343, 1994.
  16. Moore AS, London CA, Wood CA, et al:Lomustine (CCNU) for the treatment of resistant lymphoma in dogs.J Vet Intern Med,13: 395, 1999.
  17. MooreAS, Cotter SM, Rand WM, et al: Evaluation of a discontinuous treatment protocol (VELCAP-S) for canine lymphoma.J Vet Intern Med, 15: 348, 2001.
  18. Morrison-Collister KE, Rassnick KM, Northrup NC et al: A combination chemotherapy protocol with MOPP and CCNU consolidation (Tufts VELCAP-SC) for the treatment of canine lymphoma. Vet Comp Oncol, 1: 180, 2003.
  19. Mutsaers AJ, Glickman NW, DeNicola DB et al. Evaluation of treatment with doxorubicin and piroxicam or doxorubicin alonefor multicentric lymphoma in dogs. J Am Vet Med Assoc. 220: 1813, 2002.
  20. Myers NC 3rd, Moore AS, Rand WM et al: Evaluation of a multidrug chemotherapy protocol (ACOPA II) in dogs with lymphoma.J Vet Intern Med, 11: 333, 1997.
  21. NorthrupNC, Gieger TL, Kosarek CE et al: Mechloretamine, procarbazine and prednisone for the treatment of resistant lymphoma in dogs.Vet Comp Oncol. 7: 38, 2009.
  22. PostorinoNC, Susaneck SJ, Withrow SJ et al: Single agent therapy with adriamycin for canine lymphoma. J Am Anim Hosp Assoc, 25: 221, 1989.
  23. Price GS, Page RL, Fischer BM et al: Efficacy and toxicity of doxorubicin/cyclophosphamide maintenance therapy in dogs with multicentric lymphosarcoma.J Vet Intern Med, 5: 259, 1991.
  24. Rassnick KM, Mauldin GE, Al-Sarraf R et al: MOPP chemotherapy for treatment of resistant lymphoma in dogs: a retrospective study of 117 cases (1989-2000).J Vet Intern Med, 16: 576, 2002.
  25. Rassnick KM, McEntee MC, Erb HNet al: Comparison of 3 protocols for treatment after induction of remission in dogs with lymphoma. J Vet Intern Med 21:1364, 2007.
  26. Rassnick KM, Bailey DB, Malone EK et al: Comparison between L-CHOP and an L-CHOP protocol with interposed treatments of CCNU and MOPP (L-CHOP-CCNU-MOPP) for lymphoma in dogs. Vet Comp Oncol, 8: 243, 2010.
  27. SabaCF, Thamm DH, Vail DM: Combination chemotherapy with L-asparaginase, lomustine, and prednisone for relapsed or refractory canine lymphoma. J Vet Inter Med. 21: 127, 2007.
  28. Siedlecki CT, Kass PH, Jakubiak MJ et al. Evaluation of anactinomycin-D-containing combination chemotherapy protocol with extendedmaintenance therapy for canine lymphoma.Can Vet J. 47: 52, 2006.
  29. Simon D, Nolte I, Eberle N et al: Treatment of dogs with lymphoma using a 12-week, maintenance-free combination chemotherapy protocol. J Vet Intern Med, 20: 948, 2006.
  30. Simon D, Moreno SN, Hirschberger J et al: Efficacy of a continuous, multiagent chemotherapeutic protocol versus a short-term single-agent protocol in dogs with lymphoma. J Am Vet Med Assoc. 232: 879, 2008.
  31. Sorenmo K, Overley B, Krick E et al: Outcome and toxicity associated with a dose-intensified, maintenance-free CHOP-based chemotherapy protocol in canine lymphoma: 130 cases. Vet Comp Oncol, 8:196, 2010.
  32. Valerius KD, Ogilvie GK, Mallinckrodt CH et al: Doxorubicin alone or in combination with asparaginase, followed by cyclophosphamide, vincristine, and prednisone for treatment of multicentric lymphoma in dogs: 121 cases (1987-1995).J Am Vet Med Assoc, 210: 512, 1997.
  33. Van Vechten M, Helfand SC, Jeglum KA: Treatment of relapsed canine lymphoma with doxorubicin and dacarbazine.J Vet Intern Med, 4: 187, 1990.
  34. Zemann BI, Moore AS, Rand WM et al: A combination chemotherapy protocol (VELCAP-L) for dogs with lymphoma.J Vet Intern Med, 12: 465, 1998.