Primary mediastinal B-cell lymphoma

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Untreated

DA-R-EPOCH

DA-R-EPOCH: Dose Adjusted Rituximab, Etoposide, Prednisone, Oncovin (vincristine), Cyclophosphamide, Hydroxydaunorubicin (doxorubicin)

Regimen, Dunleavy et al. 2013

Phase II

• Rituximab (Rituxan) 375 mg/m2 IV over 3 hours once on day 1
• Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 200 mg/m2)
• Prednisone (Sterapred) 60 mg/m2 PO BID on days 1 to 5
• Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 1.6 mg/m2; dose was not capped)
• Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 2 hours once on day 5
• Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 40 mg/m2)

Supportive medications:

• Filgrastim (Neupogen) 300 mcg SQ once per day, starting on day 6 and continuing until ANC >5,000/uL past nadir
• Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg (or equivalent if allergic) PO once per day on 3 days per week
  • Note: It's assumed this is what the supplement for Dunleavy et al. 2013 meant by "Baxtrim (sulphametoxazole and trimethoprim)"
• Omeprazole (Prilosec) 20 mg (or equivalent) PO once per day
• Docusate (Colace) (dose not specified) and Sennosides (Senna) 2 tablets PO BID as needed for constipation
• Lactulose 20 g PO Q6H as needed for constipation
• Hepatitis B surface antigen positive patients received daily antiviral therapy until 8 weeks after completion of chemotherapy

21-day cycles x 6 to 8 cycles

Dose adjustments:

• Start cycle 1 as described above.
• Obtain CBCs twice per week for nadir measurements.
• If nadir ANC >500, increase etoposide, doxorubicin, and cyclophosphamide by one level (20%) compared to previous cycle.
• If nadir ANC <500, use same doses as last cycle.
• If nadir platelet count <25,000, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to the previous cycle.

References

1. Dunleavy K, Pittaluga S, Maeda LS, Advani R, Chen CC, Hessler J, Steinberg SM, Grant C, Wright G, Varma G, Staudt LM, Jaffe ES, Wilson WH. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013 Apr 11;368(15):1408-16. link to original article link to supplementary appendix contains verified protocol PubMed
2. Update: Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM, García-Marco JA, Castellví J, Montes-Moreno S, Batlle A, de Villambrosia SG, Carnicero F, Ferrando-Lamana L, Piris MA, Lopez A. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma. A phase II study conducted by the Spanish PETHEMA Group. Br J Haematol. 2014 Dec 18. [Epub ahead of print] link to original article PubMed

Relapsed/Refractory

Brentuximab vedotin (Adcetris)

Regimen, Bartlett et al. 2013

Phase II, <20 patients reported

This regimen was evaluated in patients with CD30+ non-Hodgkin lymphoma, as determined by immunohistochemistry.

• Brentuximab vedotin (Adcetris) 1.8 mg/kg IV over 30 minutes on day 1

21-day cycles, given until progression or unacceptable toxicity

References

1. Abstract: Nancy L. Bartlett, MD, Jeff P. Sharman, MD, Yasuhiro Oki, MD, Ranjana H. Advani, MD, Celeste M. Bello, MD, Jane N. Winter, MD, Yin Yang, MS, Dana A. Kennedy, PharmD and Eric D. Jacobsen, MD. A Phase 2 Study Of Brentuximab Vedotin In Patients With Relapsed Or Refractory CD30-Positive Non-Hodgkin Lymphomas: Interim Results In Patients With DLBCL and Other B-Cell Lymphomas. ASH Abstract 848. link to abstract

R-DHAP

R-DHAP: Rituximab, Dexamethasone, High-dose Ara-C (cytarabine), Platinol (cisplatin)

Regimen #1, Crump et al. 2014 (NCIC-CTG LY.12)

Phase III, <20 in this arm

• Rituximab (Rituxan) 375 mg/m2 IV once on day 1
• Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
• Cytarabine (Cytosar) 2000 mg/m2 IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
• Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1

21-day cycles x up to 3 cycles

References

1. Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains verified protocol PubMed

R-GDP

R-GDP: Rituximab, Gemcitabine, Dexamethasone, Platinol

Regimen #1, Crump et al. 2014 (NCIC-CTG LY.12)

Phase III, <20 in this arm

• Rituximab (Rituxan) 375 mg/m2 IV once on day 1
• Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
• Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
• Cisplatin (Platinol) 75 mg/m2 IV once on day 1

21-day cycles x up to 3 cycles

References

1. Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains verified protocol PubMed