Experimental treatments

A number of other chemotherapies are being tested in HIV-infected and non-HIV-infected people. For example, a small, phase II study has found that cyclophosphamide, doxorubicin and etoposide are comparable to standard chemotherapy.1 Studies of ECV (etoposide, cyclophosphamide and vincristine plus G-CSF) and FM (fludarabine and mitoxantrone) in HIV-negative people with lymphoma have also been promising.2 3

A study of BEMOP/CA was conducted at the Chelsea and Westminster Hospital. The regimen involves alternate weekly infusions of bleomycin, etoposide, methotrexate and vincristine with weekly infusions of cyclophosphamide and doxorubicin for 21 weeks. After two years of follow-up, 40% had died of lymphoma and the overall survival rate was 45%.4

There are a number of experimental approaches to treating NHL. It is thought that one possible cause of the over-active B-cells which are associated with NHL could be the cytokine interleukin-6 (IL-6), which stimulates B-cells and suppresses T-cells. If true, treatments that inhibit IL-6, such as antibodies against it or other cytokines such as IL-4 could be helpful for NHL. IL-6 production is also stimulated by the cytokine tumour necrosis factor α (TNF-α), so TNF-inhibitors such as pentoxifylline (Trental) or thalidomide might also be useful for people with NHL.

Anti-B4-blocked ricin is an experimental treatment which is being tested in combination with CHOP to improve response rates. Anti-B4 is an antibody that attaches specifically to malignant B-cells. Ricin is a toxin attached to the B4 antibody. In theory, the antibodies will attach to the lymphoma cells and the ricin will kill the cells. A similar drug being tested is denileukin diftitox, a fusion protein of interleukin-2 and diphtheria toxin that targets the CD25 receptor on B-cells. This has shown a response rate of 25% in a phase II study.5 Researchers are also testing newer chemotherapy drugs such as paclitaxel (Taxol), MGBG and camptothecins such as topotecan (Hycamtin).

Researchers are also investigating anti-EBV therapies as treatment options for NHL and other EBV-associated tumours.

Pegylated L-asparaginase is an anti-cancer drug which is being tested as a second-line treatment for lymphoma.

Liposomal daunorubicin (DaunoXome) has been tested as a treatment for NHL which has not responded to standard chemotherapy regimens.

A recent study has demonstrated that autologous haematopoietic stem cell transplantation is safe and effective in HIV-positive patients being treated with HAART and with high-dose chemotherapy for non-Hodgkin's lymphoma. This technique involves removal of stem cells from the bone marrow or blood of a patient before chemotherapy. Once the chemotherapy is finished, the cells are transplanted back into the patient. The transplanted cells have the ability to produce new blood cells and aid the reconsitutution of the immune system by replacing the cells that are killed during the course of drug treatment.6

References

  1. Sparano JA et al. Phase 2 trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with poor-prognosis, intermediate-grade non-Hodgkin lymphoma: an Eastern Cooperative Oncology Group trial (E3493). Blood 100(5): 1634-1640, 2002
  2. Sehn LH et al. High dose ECV consolidation chemotherapy for poor prognosis lymphoma. 35th Annual Meeting of the American Society of Clinical Oncology, Atlanta, abstract 47, 1999
  3. Velasquez W et al. SWOG 95-01: a phase II trial of a combination of fludarabine and mitoxantrone (FN) in untreated advanced low grade lymphoma. An effective, well tolerated therapy. 35th Annual Meeting of the American Society of clinical oncology, Atlanta, abstract 27, 1999
  4. Bower M et al. Weekly alternating combination chemotherapy for good prognosis AIDS-related lymphoma. Eur J Cancer 36: 363-367, 2000
  5. Dang NH et al. Phase II study of denileukin diftitox for relapsed/refractory B-cell non-Hodgkin's lymphoma. J Clin Oncol 22: 4095-4102, 2004
  6. Gabarre J et al. High-dose therapy plus autologous hematopoietic stem cell transplantation for human immunodeficiency virus (HIV)-related lymphoma: results and impact on HIV disease. Haematologica 89: 1100-1108, 2004
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