Combination chemotherapy followed by an immunotoxin (anti-B4-blocked ricin) in patients with indolent lymphoma: results of a phase II study.

Abstract

The purpose of this article was to evaluate the antitumor effects of a combination chemotherapy program based on ProMACE (prednisone, methotrexate, doxorubicin [Adriamycin], cyclophosphamide, etoposide) followed by a B cell-specific immunotoxin in the treatment of patients with advanced-stage indolent histology non-Hodgkin's lymphomas. We performed a prospective phase II clinical trial in a referral-based patient population. After confirmation of diagnosis and staging evaluation, 44 patients (10 small lymphocytic lymphoma, 27 follicular lymphoma, 7 mantle cell lymphoma; 30 without prior therapy, 14 previously treated) received six cycles of ProMACE-CytaBOM (cytarabine, bleomycin, vincristine [Oncovin], mechlorethamine) combination chemotherapy (with etoposide given orally daily for five days) followed by a 7-day continuous infusion of anti-B4-blocked ricin immunotoxin at 30 microg/kg/day given every 14 days for up to six cycles. A complete response was achieved in 25 of 44 patients (57%), 21 from the chemotherapy alone, 3 converted from partial to complete response with the immunotoxin, and 1 patient became a complete responder after a surgical procedure to remove an enlarged spleen that was histologically negative for lymphoma. With a median follow-up of 5 years, 14 of 25 complete responders have relapsed (56%); median remission duration was 2 years, and overall survival was 61%. Forty-two percent of the complete responders have been in continuous remission for more than 4 years. The median number of courses of immunotoxin delivered was two usually because of the development of human anti-ricin antibodies. ProMACE-CytaBOM plus anti-B4-blocked ricin does not produce durable complete remissions in the majority of patients with indolent lymphoma. However, the remissions appear quite durable (> 4 years) in about 40% of the complete responders.

• Authors: D L Longo, P L Duffey, J G Gribben, E S Jaffe, B D Curti, B L Gause, J E Janik, V M Braman, D Esseltine, W H Wilson, D Kaufman, R E Wittes, L M Nadler, W J Urba
• Journal: Cancer journal (Sudbury, Mass.) (Cancer J) 2000 May-Jun Vol. 6 Issue 3 Pg. 146-50 ISSN: 1528-9117 [Print] United States
• PMID: 10882329 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article)

Chemical References

• Antineoplastic Agents
• Immunoconjugates
• Immunotoxins
• anti-B4 blocked ricin immunoconjugate
• Cytarabine
• Bleomycin
• Vincristine
• Etoposide
• Doxorubicin
• Cyclophosphamide
• Ricin
• Prednisone
• Methotrexate

Topics

• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bleomycin (therapeutic use)
• Cyclophosphamide (therapeutic use)
• Cytarabine (therapeutic use)
• Disease-Free Survival
• Doxorubicin (therapeutic use)
• Etoposide (therapeutic use)
• Female
• Humans
• Immunoconjugates (therapeutic use)
• Immunotoxins (therapeutic use)
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, mortality)
• Lymphoma (drug therapy, mortality)
• Lymphoma, Follicular (drug therapy, mortality)
• Lymphoma, Mantle-Cell (drug therapy, mortality)
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Prednisone (therapeutic use)
• Ricin (therapeutic use)
• Time Factors
• Treatment Outcome
• Vincristine (therapeutic use)