TreatmentUpdate 55 - Vol. 7, No. 1 - January 1995
Sean Hosein

Researchers in France have created an antibody that attacks the cytokine IL-6 (interleukin 6). Their antibody, called BE-8, was originally made by cells from mice. This antibody had been tested on non-HIV-infected patients with cancer and did not appear to cause any serious toxicity. Our report provides results from a study called ANRS 018.

* TYPE OF SUBJECTS

Researchers enrolled 11 HIV-infected subjects (9 males, 2 females) with B cell lymphoma in this study. All subjects had less than 40 CD4+cells when they entered the study. Researchers did not release the subjects' CD8+ cell counts. Before entering the study five subjects had received chemotherapy but despite treatment their tumours grew. While receiving infusions of BE-8 subjects did not receive chemotherapy or radiation one month before or during this study. Subjects had tumours in a variety of places including the lung, face, stomach and testicles.

* DRUGS AND MONITORING

Researchers gave the subjects 125 ml of salt solution which contained BE-8. Technicians took blood samples from subjects to measure a protein called CRP (c-reactive protein). Production of CRP in the liver falls when IL-6 levels decline. As well, doctors also compared the size of tumours before and after subjects received BE-8. At first "3 [subjects received] 10 mg/ day of BE-8." Since CRP levels were still high, the dose of BE-8 was increased to 20 mg/day and up to 40 mg/day if CRP levels did not fall. Subjects were supposed to receive the drug for at least 3 weeks or 1 cycle. Some subjects received the drug for longer periods of time.

* RESULTS

During the first 21 days of the study about 1/2 the subjects stabilized. Only 4 subjects received BE-8 for more than 21 days. The drug caused CRP levels in the blood to fall and also delayed the growth of the cancer for between 57 and 91 days.

* SYMPTOMS

Doctors found that 4 subjects with symptoms of lyrnphoma (such as fever and night sweats) had some relief when they received BE-8. Other subjects had increased appetite and weight. Those subjects who received more than 1 cycle of BE-8 continued to gain weight.

* SIDE EFFECTS

Subjects did not report many side-effects. One subject had headaches "1 hour after" receiving BE-8. No subject had life-threatening infections while in the study. Researchers did allow subjects to use anti-PCP/toxo drugs. All subjects had less than normal levels of platelets (needed for clotting blood) but they did not suffer from prolonged bleeding. Blood levels of white cells called neutrophils fell in subjects but this did not cause any complications. Two subjects rnade antibodies that attacked BE-8 but this did not appear to cause increased growth of the tumours.

* SUMMARY

While infusions of anti-IL-6 appeared to stop the growth of tumours in some subjects, eventually the tumours continued to grow. BE-8 did affect symptoms of Iymphoma clearing "fever, sweats and [weight loss]". The French research team suggested that combination treatment of AIDS-related Iymphoma with BE-8 and anti-cancer drugs should be tested to see if survival is lengthened. BE-8 may also provide some relief from symptoms for other subjects with cancer.

* CYTOKINES AND CANCER

Clearly, anti-IL-6 had only weak anti-cancer effects. While researchers have documented changes in the type of cytokines released in patients with HIV/AIDS, trying to use just one type of anti-cytokine is not enough. Effective treatment may require a more sophisticated approach, perhaps blocking the effects of other cytokines such as IL-4 and IL-10. The monoclonal antibody used in this study was made and purified by technicians associated with this trial.

REFERENCES:

1. Clerici M, Ferrario E, Trabattoni D, et al. Multiple defects of T helper cell function in newly diagnosed patients with Hodgkins disease. European Journal of Cancer 1994;30A(10):1464-1470.

2. de Hon FD, Ehlers M, Rose-John S, et al. Development of an interleukin (IL) 6 receptor antagonist that inhibits the growth of human myeloma cells. Journal of Experimental Medicine 1994; 180:2395-2400.

3. Emille D, Wijdenes J, Gisselbrecht C, et al. Administration of an anti-interleukin-6 monoclonal antibody to patients with Acquired Immunodeficiency Syndrome and Iymphoma: effect on Iymphoma growth and on B clinical symptoms. Blood 1994;84(8):2472-2479.

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Copyright © 1995 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca